Index 1081

Index

A Adenoma(s) (Continued) Adjuvant trastuzumab

ABCSG (Austrian Breast and Colorectal Cancer nipple, 128 duration of, 767
Study Group), 740–742, 740f, 742f versus Paget disease, 171–172 predictors of, 767
Abdominal transverse rectus abdominis pituitary, nipple discharge due to, 66 in small, lymph node-negative tumors, role of,
myocutaneous flap, surgical technique of, tubular, 89 767
484–485, 486f–487f ADH. See Atypical ductal hyperplasia. AdnaTest (AdnaGen), for CTC detection, 861t, 862
Aberrations of Normal Development and Involution Adhesion molecule (EpCAM), in circulating tumor Adnexal tumors
(ANDI) classification, of benign breast disease, cells, 860–861 benign, 183–184, 183f
79, 80t Adjuvant chemotherapy, 753 malignant, 187, 187f
Abortion classification of, 325t Adolescent hypertrophy, 92
induced, as risk factor, 215–216 history of, 16 Adoptive T-cell therapy, 930–931
therapeutic, for pregnancy-associated breast for locally advanced breast cancer, 821 Ado-trastuzumab emtansine (T-DM1), 292
cancer, 998 randomized clinical trials of, 821t mechanism of action of, HER signaling and, 293f
Abscess, subareolar, 180–181, 180f mastectomy or radiation after, 729 Adrenal cortex neoplasms, gynecomastia due to, 107
chronic, 96–98 Adjuvant endocrine therapy, 736–751 Adrenal cortical steroids, in regulation of mammary
AC (Axillary clearance). See Axillary lymph node adherence to, 750–751 gland, 23–24
dissection. aromatase inhibitors for, 737 Adrenalectomy, for breast cancer, history of, 15–16,
Acanthosis nigricans, 190 candidate for, 736 907
Accelerated partial breast irradiation (APBI), for ductal carcinoma in situ, 748–749 Adriamycin. See Doxorubicin.
668–670, 706–712, 707f hormone receptor status in, 747–748 Advanced local breast cancer, surgical procedures for,
applicator, 707–709, 709t for invasive early-stage breast cancer, 737–747 778–801
expert consensus statements in, 710, 712t mechanism of action for, 737, 737t Afimoxifene, for refractory mastalgia, 86
external-beam, 709–710, 711t for postmenopausal women, 743 After Mapping of the Axilla: Radiotherapy or
future directions of, 710–712 rationale for, 736 Surgery Trial (AMAROS), 630
interstitial, 706–707, 708t regimen for premenopausal women with Age
technique of, 706 early-stage invasive hormone receptor- bilateral breast cancer and, 967
techniques for delivery of, 669–670 positive breast cancer, 745–746, 746f breast carcinoma, as risk for, 333–334
3D conformal radiation therapy as, 669 risk of recurrence in women treated with, 747 delayed diagnosis and, 1061–1062, 1065–1066,
Accessory areolar glands (of Montgomery), 21 side effects of 1065f–1066f
Accessory axillary breast tissue, 39f, 41 bone and joint pain as, 750 at diagnosis, as prognostic factors, 255–256
Accessory breast. See Polymastia. cardiovascular disorders as, 749–750 of patient, in breast conserving surgery and
Accessory nipples. See Polythelia. loss of bone mineral density, osteoporosis, and radiation, 695
Acellular dermal matrix fractures as, 750 Aging male, gynecomastia in, 114–115
reconstruction with, 480–481 menopausal symptoms as, 749 Agnew, D. Hayes, 9
surgical technique for, 481, 482f mood disturbances as, 750 Agnew Clinic, 9, 10f
ACOSOG (American College of Surgeons Oncology quality of life as, 750 AH. See Atypical hyperplasia.
Group) sexual dysfunction as, 749 AIs. See Aromatase inhibitors.
ACOSOG Z0010 trial, on sentinel thromboembolism as, 749 AKT inhibitors, for metastatic breast cancer, 900t
lymphadenectomy, 628 uterine disorders as, 749 Alcohol consumption, breast cancer risk and,
ACOSOG Z0011 trial, on sentinel timing of initiation of, 747 216–217
lymphadenectomy, 628–630, 629t Adjuvant hormonal therapy, for locally advanced Aldefluor assay, 308–309
Actinic keratosis, 192–193, 193f breast cancer, 821–822 ALH. See Atypical lobular hyperplasia.
Acupuncture, for acute and chronic pain, 1036 Adjuvant Lapatinib and/or Trastuzumab treatment Alkylating agents, for metastatic breast cancer, 893
Acute radiation dermatitis, 716–717, 718f–719f optimisation (ALTTO) trial, 767 Allergic contact dermatitis, of nipple, 179–180,
Adaptive immunity, 924–925, 925f Adjuvant radiation therapy 180f
Adenocarcinoma, mammography of, 346–347 for early breast cancer, 652–653, 652t ALMANAC (Axillary Lymphatic Mapping Against
Adenoid cystic carcinoma, 151, 151f for male breast cancer, 978 Nodal Axillary Clearance) trial, 521
Adenolipoma, 90 Adjuvant systemic therapies ALN(s). See Axillary lymph node(s).
Adenoma(s) for early-stage breast cancer, 752–762 ALND. See Axillary lymph node dissection.
ductal, 128 for male breast cancer, 978 al-Quanum fil-Tib, 4
lactating, 126 Adjuvant Tamoxifen: Longer Against Shorter Alveolar development, during pregnancy, 22, 23f
(ATLAS) trial, 971 Alveolus(i), in breast development, 44
Adjuvant Tamoxifen Treatment-offer more? (aTTom) AMAROS (After Mapping of the Axilla:
trials, 918 Radiotherapy or Surgery) Trial, 630
Page numbers followed by f indicate figures; b, boxes; Adjuvant therapy, psychologic distress due to, Amastia, 41, 42f, 177
t, tables; e, online content. 1042–1043 Amenorrhea, chemotherapy-related, 1017

1081
1082 Index

American College of Radiology Imaging Network, Androgen receptor, 280. See also Progesterone Arimidex-Nolvadex (ARNO) trial 95, 740–741,
644 receptor(s). 740f
American College of Surgeons Oncology Group Androgen resistance syndromes, gynecomastia due Armamentarium Chirurgicum, 4–5
(ACOSOG), 449, 614–615, 650–651, to, 109 Armpit, anatomy of, 26
828–829 Anesthesia ARNO. See Arimidex-Nolvadex (ARNO) trial 95.
Z0010 trial, on sentinel lymphadenectomy, 634, for biopsy, 383 Aromatase activity, increased, gynecomastia due to,
634f for modified radical mastectomy, 457 109
Z0011 trial, on sentinel lymphadenectomy, 594 during pregnancy, 995 Aromatase inhibitors (AIs), 231–232, 272, 737t,
American Geriatrics Society, 653–654 Angiogenesis, 320 757, 978–979
American history, of surgical quality measurement, inducing, in cancer cells, 284 biomarkers suggestive of benefit from,
500 Angiogenic dormancy, 320 747–748
American Joint Committee on Cancer (AJCC), Angiogenic switch, 319–320 as breast cancer therapy, 932
429–430, 430t, 617 mechanism of, 320 for chemoprevention, 558
American Recovery and Reinvestment Act of 2009, Angiomatosis, 160 in early aromatase inhibitor trials, 911
501 Angiosarcoma (AS), 160–161, 160f estrogen deprivation with, 276
American Society of Breast Surgeons (ASBrS), 499 radiation therapy and, 186–187, 186f exemestane, 232
American Society of Clinical Oncology (ASCO), Annual National Cancer Database (NCDB) history of, 908
199, 200f, 289, 954 Benchmark Reports, 436f for longer than 5 years, 742–743
2013 Clinical Practice Guideline, 233, 233b, 234t Annular erythema, 190 recommendation of, 236
American surgery, in nineteenth century, 8–9, 9f Ansa pectoralis, 27 side effects of, 911
Anaerobic glycolysis, 285 Anterior circumflex humeral arteries, 26 steroidal versus nonsteroidal aromatase inhibitors
Analgesics, for breast pain, 85 Anterior cutaneous nerves, 25 as, 911
Anastrozole Anterior group, of axillary lymph nodes, 30, 30f–31f tamoxifen and, sequential therapy with, 739–741,
for breast cancer, 232 Anterior intercostal arteries, 24f, 25 741t
osteoporosis and, 1016 Anterior mediastinal nodes, 35 therapy for 5 years, 738–739, 740t
Anatomy Anthracycline-containing regimens, 325 as type of endocrine therapy, 737
of axilla, 26–28 Anthracycline-cyclophosphamide-taxane, trials of, Arthralgias, musculoskeletal complaints, 1017
boundaries of, 26, 26f 823 AS (angiosarcoma), 160–161, 160f
contents of, 26–27, 26f–27f Anthracyclines, 753, 952–953 radiation therapy and, 186–187, 186f
fascia of, 27–28, 27f for breast cancer, 781–782 Aselli, Gasparo, 514
lymph nodes of, 30–31, 30f–31f for metastatic breast cancer, 890–891 “Aspiration gun,” for fine-needle aspiration biopsy,
of breast Anthropometry, breast cancer risk and, 211–214 377, 378f
in active mammary gland, during pregnancy Anti-α lactalbumin DNA vaccine, 932 Asymmetry, mammography of, 352, 353f
and lactation, 22–23, 23f Antiandrogen therapy, for metastatic breast cancer, ATAC trial. See Arimidex, Tamoxifen, Alone or in
blood supply of, 28–29, 28f 900t Combination (ATAC) trial.
extent and location in, 21 Antiangiogenic therapy Athelia, 177
fascial relationship of, 28 for metastatic breast cancer, 899–901, 900t ATLAS (Adjuvant Tamoxifen: Longer Against
form and size in, 20–21, 22f in treatment of breast cancer, 851 Shorter) trial, 971
gross, 20–21 Antibiotics, for mastitis and breast abscess, 94 ATM, mutation in, 248
in inactive mammary gland, 21–22, 23f Antibody-dependent cell-mediated cytotoxicity aTTom (Adjuvant Tamoxifen Treatment-offer more?)
innervation of, 29 (ADCC), 928 trials, 918
lymphatic drainage of, 30–36 Antibody-drug conjugates, for metastatic breast Atypical ductal hyperplasia (ADH), 91, 118, 122f,
microscopic, 21–29 cancer, 900t 133–134, 133f
nipple and areola in, 21 Antidepressants, for vasomotor symptoms, Atypical hyperplasia (AH), 119–121, 121f
venous drainage of, 35f, 36 1025–1026, 1026t breast cancer risk and, 209
of thoracic wall, 24–26, 24f–25f Antifolate inhibitors, for metastatic CNS disease, extent of, 266–267, 267t
lymph nodes of, 34–35 953 invasive breast cancer, in women with, 227–228,
topographic surgical, 388–391 Antigen-specific Tregs, 924–925 227f
lymphatic drainage and routes for metastases Anti-HER2 therapy, 848–851, 849t–850t SERMS in lobular carcinoma in situ and,
in, 390–391 Antihormone therapy, long-term, mechanisms of 225–227
neurologic innervation of pectoral muscles in, drug resistance to, 276–278, 278f Atypical lobular hyperplasia (ALH), 91, 121, 121f
388–390, 389f Antimetabolites, for metastatic breast cancer, Atypical vascular lesion, 186
vascular distribution in, 390 893–894 Auchincloss techniques, 392–393
Ancient civilizations, history of breast cancer therapy fluoropyrimidines as, 893–894, 894f Augmentation mammaplasty, 489–490
in, 1–2 gemcitabine as, 894 Augmented breast, breast cancer in, 989–990,
Babylonian, 1 Antral follicle count, 773–774 990f
Chinese, 1 APBI. See Accelerated partial breast irradiation. Austrian Breast and Colorectal Cancer Study Group
in classic Greek period, 1–2 Apical nodes, anatomy of, 31 (ABCSG), 740–742, 740f, 742f
Egyptian, 1, 2f Apical nodes, in lymphedema, 517, 518f Autologous breast flaps, 490
in Greco-Roman period, 2, 2f–3f Apocrine metaplasia, 88 Automated Quantitative Analysis (AQUA)
ANDI (Aberrations of Normal Development and Apocrine secretion, 22–23 technology, 262
Involution) classification, of benign breast Apoptosis, 284 Avastin. See Bevacizumab.
disease, 79, 80t estrogen-induced, 278–280, 279f Avery, Oswald, 240
Androgen(s), 975 Architectural distortions, mammography of, 352, Avicenna, 4
for breast pain, 84 353f Axilla
for metastatic disease, 910 Areola, anatomy of, 21 anatomy of, 26–28, 592–597, 592f, 593t
Androgen biosynthesis, hereditary defects of, Arimidex, Tamoxifen, Alone or in Combination boundaries of, 26, 26f
gynecomastia due to, 108 (ATAC) trial, 738–739, 739f contents of, 26–27, 26f–27f
 Index 1083

Axilla (Continued) Axillary nerve, 27f Benign breast disease (BBD) (Continued)
evaluation of, 592–597, 592f, 593t Axillary nodal disease cyclic, 79–80
lymph nodes of, 30–31 patterns of, 540t etiology of, 79–92
management of, 828–830 as prognostic indicator, 540–541 interventions for, 82t
in node-negative patients, 828–829 survival and, 540, 540f management of, 82–87
in node-positive patients, 829–830 tumor size and, 532–533, 533t endocrine therapy for, 83–84
in patients undergoing neoadjuvant therapy, Axillary nodal groups, topographic anatomic nonendocrine therapy for, 84–85
830 depiction of, 390, 391f nutritional therapy for, 82–83
selective, 599–601, 601t Axillary nodal status, survival rates of, after modified for refractory mastalgia, 85–87
sentinel lymph node procedure and, staging of, radical mastectomy, 446t nomenclature for, 80
854–855 Axillary node recurrences, 811 noncyclic, 80
suspensory ligament of, 28 Axillary radiotherapy, 597–598, 597t pathogenesis and etiology of, 80
Axillary artery, 26, 26f–27f Axillary recurrences, after mastectomy, 983 pathophysiology of, 80–82
Axillary clearance (AC). See Axillary lymph node sentinel lymph node (SLN) biopsy and, 983 endocrine influences in, 80–81
dissection. Axillary reverse mapping, for lymphedema, 517, nonendocrine influences in, 81–82
Axillary control. See Axillary lymph node 519f, 527 complex fibroadenoma as, 89
dissection. Axillary reverse mapping (ARM), 627 epithelial hyperplasia as, 89b, 92
Axillary evaluation, of early breast cancer, Axillary sheath, 26 fat necrosis as, 92
649–652 Axillary space, 592 fibroadenoma as, 89–90
Axillary fasciae, anatomy of, 27–28 extension of the primary neoplasm into, 387 fibroadenomatosis (fibroadenomatoid mastopathy)
Axillary granular parakeratosis, 182–183 Axillary staging, 784–786 as, 89
Axillary lymph node(s) (ALNs), 592 Axillary surgery, for metastatic disease, of intact hamartoma as, 90
abnormal, mammography of, 353, 354f breast primary, 868 histopathology of, 116–118, 117f–118f
clinical staging of, 251 Axillary tail (of Spence), 20–21 lactating adenoma as, 89–90
grouping of, 516–517, 518f Axillary vein, 26–27, 30f, 36 nipple discharge due to, 91–92
lymphedema and, 626–627 Axillary vein group, of axillary lymph nodes, 30, nipple inversion as, 92
management of, 617–618 30f, 35f nonproliferative lesion as, 88–90, 91t
micrometastases to, 254 apocrine metaplasia as, 88
palpable, 614 B cysts as, 88
radiation treatment of, 618 Babylonian civilizations, history of breast cancer duct ectasia as, 88
status, assessment of, 845–846 therapy in, 1 mild ductal epithelial hyperplasia as, 88
Axillary lymph node dissection (ALND), 460–461, Bacillus Calmette-Guerin (BCG), 780 periductal mastitis as, 88
604, 650–651, 1033 Baclesse, François, 15 proliferative lesions as
completion, for positive sentinel node, Banks, Mitchell, 7–8 with atypia, 91
678–680 Basal cell carcinoma, 193, 193f atypical ductal hyperplasia as, 91
lymphedema and, 515t, 521 Basal lamina, 22 atypical lobular hyperplasia as, 91
with skin-sparing mastectomy, 400 Basal-like breast cancers, 903 flat epithelial atypia as, 91
therapeutic role of, 598–599 Basement membrane, 22 without atypia, 90–91
therapeutic value of, 590–603, 592f Batson plexus, 29 florid ductal epithelial hyperplasia as, 90
without completion, of positive sentinel node, Batwing mastopexy lumpectomy, 471f intraductal papilloma as, 90–91
677–678 Batwing technique, 581 radial scar and complex sclerosing lesions as,
Axillary lymph node (ALN) micrometastases BBB (Blood-brain barrier), chemotherapeutic agents 90
classification of, 631–632 that cross, 953t sclerosing adenosis as, 90
detection and significance of, 631–636 BBD. See Benign breast disease. pseudoangiomatous stromal hyperplasia as, 90
frequency and prognostic significance of, 631, BCDDP (Breast Cancer Detection and subareolar abscess and fistula as, 92
632t Demonstration Project), 1067–1068, tubular adenoma as, 89
logistical hurdles in the detection of, 633 1075–1076, 1078 Benign cysts, 183–184, 183f
Ludwig studies of, 632–633 BCL2 and survivin, 305 Benign melanocytic lesions, 192, 192f
occult, classification by frequency of, 632 BCPT. See Breast Cancer Prevention Trial. Benign peripheral nerve sheath tumors, 162
prospective studies of, 634–635, 634t–635t BCQ (Breast Cancer Chemotherapy Questionnaire), Benzopyrones, for lymphedema, 526
by size of metastasis, 631 1040 Bergenstal, D.M., 907
staging of, 633 BCRAT model, 1004 Bevacizumab (Avastin), 328
unresolved controversies of, 635–636 BCS (breast conserving surgery). See Breast for metastatic breast cancer, with taxanes, 892,
Axillary lymphadenectomy, 784–785. See also conservation therapy. 899–900
Axillary lymph node dissection. BCT. See Breast conservation therapy. randomized trial of, 823
Axillary lymphadenopathy, with unknown primary. Beatson, G., 907 Biased coin randomization, 372
See Axillary metastasis, of unknown primary. Becker nevus, 178 Bidirectional lymphatic flow, 390
Axillary Lymphatic Mapping Against Nodal Axillary ben Abbas, Haly, 4 BIG (Breast International Group), 1-98 study, 739,
Clearance (ALMANAC) trial, 521, 594, Benchmark, 508–509 739f–740f, 916
626–627, 630, 828–829 Benelli lift-type procedure, 471f Bilateral breast cancer, 967–973
Axillary metastasis Benign breast disease (BBD), 116 advanced imaging and adjuvant therapy on,
occult, 631 adenolipoma/lipoma as, 90 970–971
of unknown primary, 1000–1003 adolescent hypertrophy as, 92 in lobular carcinoma in situ, 970
diagnosis of, 1000–1001, 1001f breast cancer risk and, 209, 210t pathogenic mutations of, 968
imaging in, 1000–1001, 1002f–1003f breast pain as, 79–87, 81f prognosis of, 971–972
pathologic evaluation, 1001 algorithm of, 87f risk factor(s) for, 967–970
incidence of, 1000, 1001f classification of, 79–80, 80t age as, 967
management of, 1001–1003 clinical assessment of, 79–80 BRCA1 and BRCA2 mutations as, 967–968
1084 Index

Bilateral breast cancer (Continued) Bisphosphonates (Continued) Bowen disease, 172, 192–193, 193f
family history as, 968 clinical trials on adjuvant, in breast cancer, Boyd, Stanley, 272, 907
hereditary breast cancer as, 967–968 769–771, 770t Brachial plexopathy, 721, 1035
invasive lobular carcinoma as, 969–970 clodronate, trial using, 769–771 Brachial plexus, 27, 27f
radiation exposure as, 969 consideration of, 772 Brachial plexus injury, during mastectomy, 497
risk of, 968t in early breast cancer, 769–772 Brachiocephalic lymph nodes, 35
tamoxifen as adjuvant therapy for, 971 ibandronate, trial using, 771 Brachytherapy, 669–670, 669f
Bilateral deep inferior epigastric perforator flaps, individual patient-level data meta-analysis of, 771 Brain metastases-free survival (BMFS), 806
487f mechanism of action, 769 Brain metastasis(es), 805–806
Bilateral prophylactic mastectomy, risk reducing for osteoporosis, 1016–1017 anticonvulsants for, 947
surgery, 246 rationale for an anticancer effect for, 769 chemotherapy for, 952–955, 953b, 953t
Bilateral reduction mammoplasty, 490f safety of, 772 clinical presentation of, 943
Bilateral salpingo-oophorectomy, risk reducing types of, 769 corticosteroids for, 946–947
surgery, 245–246 zoledronate, trial using, 771 diagnostic evaluation of, 944
Billroth, Theodor, 8 BLN (Breast Lymph Node) Assay, 542 lapatinib for, 899
Biological marker(s), 531–542, 536f, 538f Block, G., 907 multiple, surgery for, 950
bone marrow micrometastases as, 536–537 Blood supply, of breast, 28–29, 28f prognosis of, 946
cathepsin D as, 537–538 Blood-brain barrier (BBB), chemotherapeutic agents radiation sensitizers for, 955
molecular profiling as, 539 that cross, 953t recurrent, 955–956
molecular subtype as, 538, 538f Blue dye transit, schematic diagram of, 605f risk factors for, 942
plasminogen activator inhibitor as, 537–538 Blue dyes, for sentinel lymph node, 650, 651f single, surgical intervention for, 949–950
in prognosis, 537–538 BMD (bone mineral density) stereotactic radiosurgery for, 950–952
tumor markers as, 537–538 breast cancer risk and, 217 surgery for, 949–950
urokinase plasminogen activator as, 537–538, loss of, in AI therapy in postmenopausal women, treatment of, 945–960
537f 750 BRCA mutation, 655, 721
Biological predeterminism, theory of, 1075 monitoring of, 1016 history of, 453
Biology, tumor, 691–692 Body image, in breast cancer survivorship, pregnancy-associated breast cancer and, 998
Biopsy 1052–1053 BRCA1, 294–298, 456, 456f
anesthesia for, 383 Body weight, breast cancer risk and, 1046 breast cancer risk and, 229
core, 335–336 Boerhaave, Hermann, 5 in breast conserving surgery and radiation, 696
core needle, 379–382, 380t, 644 Bone, in breast cancer, 769 contralateral breast cancer and, 967–968
imaging-guided, 357–358, 358f Bone marrow micrometastases, 536–537 immunophenotypes of, 298t
cytopathology of, 378, 378f Bone marrow transplant, 755 mutation in, 247
direct smear for, 379 Bone metastasis(es), 804–805 psychological distress about, 1041–1042
evolution of simple mastectomy, with sentinel bisphosphonates for, 901 BRCA2, 294–298
lymph node, 449 in breast cancer, management of, 876–884 in breast cancer, 229
excisional, 335–336 clinical presentation of, 877 in breast conserving surgery and radiation, 696
fine-needle aspiration, 335–336, 377–378, 378f, diagnosis of, 877–878 contralateral breast cancer and, 967–968
380t new treatment modalities for, 883 immunophenotypes of, 298t
accuracy of, 377–378 pathophysiology of, 876–877 mutation in, 247
false-negative, 1070–1071 radiotherapy of, 879–880 pregnancy-associated breast cancer and, 998
procedure of, 377 alone, 879 psychological distress about, 1041–1042
fluid aspiration for, 379 postoperative, 879–880 Breast(s)
indications and techniques for, 385 radiopharmaceuticals in, 880 anatomy of, 20–36
of intraductal lesions, minimally invasive retreatment with, 880 in active mammary gland, during pregnancy
techniques for, 75–76 side effects of, 880 and lactation, 22–23, 23f
intraoperative ultrasound guidance for, 384 recommendations on, 883–884 after menopause, 23–24
magnetic resonance imaging-guided, 382 surgical management of, 878 gross, 20–21
open surgical, 382–385, 383f for pathologic fractures, 878 in inactive mammary gland, 21–22, 23f
pleural needle, 937, 938f prophylactic surgery in, 878 microscopic, 21–29
during pregnancy, 994–995 systemic osteoclast inhibitors for, 880–883, nipple and areola in, 21
radioactive seed localization of, 384–385, 883t arteries and nerves of, 389f
385f bisphosphonates as, 880–882, 881t blood supply of, 28–29, 28f
random periareolar, 64 denosumab as, 882–883 compression, during mammography, 337
sentinel lymph node (See Sentinel lymph node pamidronate for, 901–902 spot, 339, 340f
biopsy) Bone mineral density (BMD) ductal carcinoma in situ of, 562–575
stereotactic, 644 breast cancer risk and, 217 extent and location of, 21
stereotactic core needle, 381–382 loss of, in AI therapy in postmenopausal women, fascial relationship of, 28
surgical excisional, 336 750 form and size of, 20–21, 22f
ultrasound-guided, 380–381 monitoring of, 1016 imaging screening and diagnosis of, 337–361
wire-guided localization of, 383, 384f Bone morphogenic proteins (BMP), 286–287 innervation of, 29
BI-RADS (Breast Imaging Reporting and Data Bone remodelling, 876 lobular carcinoma in situ of, 553–561
System), 339 Bone resorption, 876 lymphatic drainage of, 30–36
“Bird’s beak” deformity, 578, 578f Bony metastases. See Bone metastasis(es). lymph flow in, 30f–31f, 32–34
Bisphosphonates Boomerang incision, 647–648, 647f sentinel lymph node biopsy in, 31–32
benefit in postmenopausal women, 771–772 BOOP (bronchiolitis obliterans organizing removal of, 458
for bone metastases, 880–882, 881t, 901 pneumonia), due to radiation therapy, 722 stem cells in, 308–309
breast cancer risk and, 217 Boost treatment planning, 667, 667f supernumerary (accessory) (See Polymastia)
 Index 1085

Breast(s) (Continued) Breast cancer (Continued) Breast cancer (Continued)

surgery of, 774 frequently altered molecular pathways in, 304 oncofertility options for young women with,
ultrasound of, 337 genetic abnormalities in, 298–299 773–777
venous drainage of, 28–29, 35f genetic and epigenetic alterations of, 322 Oncotype Dx for, 259–261
Breast abscess, 93–103 genetics oral contraceptives and postmenopausal hormone
periductal, 96–98 cancer genetics counselor role in, 237–239 therapy, 215
subareolar, 180–181, 180f classifying variants, 242, 242t, 243f pharmacologic interventions for breast cancer risk
chronic, 96–98 genetic testing technology, 240–242 reduction, 232–236
Breast augmentation, delayed diagnosis with, 1071 large rearrangements, 241–242 physical activity for, 216
Breast biomarker immunocytochemistry, 197–206 next generation sequencing, 241, 241f predictive factors for, 251b
American Society of Clinical Oncology/College of Sanger sequencing, 240–241 preeclampsia in, 215
American Pathologists recommendations on, identifying mutation carriers, 238t–240t, prevention trial in, 222–224
199, 200f 239–240 primary prevention of, 219–236
correlation with Oncotype Dx, 199–200 managing cancer in mutation carriers, 246–249 progression of, 322
estrogen receptor, 197–198 syndromes, 246–249 proliferation-inducing pathways in, 282–283
progesterone receptor, 198 managing cancer risk, 244–246, 244t prominent driver mutations in, 285
receptor status assessment, 198 chemoprevention, 245 radiation therapy of, 324
scoring of receptor expression in, 198–199 enhanced surveillance, 245 raloxifene for, 221–222
Breast cancer, 752, 769 reproductive and lifestyle factors, 244–245 reconstruction, timing of, 788–789
actionable alterations in, 299 risk reducing surgery, 245–246 reconstruction for, 788–789
activation of invasion and metastasis of, 284 multigene panels, 243–244, 244f regional malignancies of, 778–801
advanced/metastatic, markers for the management syndromes/genes/pathology/counseling/testing/ reproductive factors of, 209–211
of, 306 treatment, 237–249, 238f, 238t reprogramming energetics of, 285–286
alcohol consumption and, 216–217 value of genetic testing, 237 resisting cell death of, 284
American Society of Clinical Oncology 2013 variants of uncertain significance, 242–243 risk factors for, 211–218, 211t–213t, 315,
Clinical Practice Guideline, 233, 233b, 234t genome instability and mutation of, 284–285 316t
angiogenic therapy for, 328 global experience with sentinel lymphadenectomy SERMs, indications and contraindications, for
anthracyclines for, 781–782 in, 607–609 risk reduction with, 228–229, 228b
anthropometry and, 211–214 hallmarks of, 282–286, 283f, 322 SERMS in lobular carcinoma in situ and atypical
aromatase inhibitors in, 231–232 hereditary, 294–298, 296t, 297f, 300f hyperplasia, 225–227
associated with fibroadenoma, 268, 270t heterogeneity of, 324–325 skin grafts of, 790f
benign, 209, 210t hormone receptor, 319 smoking in, 217
bilateral, 967–973 identification of sentinel node in, 607 sociodemographic factors of, 208–209
biological agents used in treatment of, 774 immune destruction of, 286 stage, assessment and designation of, 531–552
biomarkers used in clinical management of, immunotherapy for, 328–330 stem cells in, 309–314, 309f
305–306, 306t index, 261–262 subtypes of, 752
bisphosphonates, 217 induced abortion, 215–216 neoadjuvant chemotherapy by, 847–848,
bone mineral density, 217 inducing angiogenesis of, 284 848t
cells, gene expression profiling of, 858–859 inflammatory, 865 by race, ethnicity and geography, 207–208,
checkpoint inhibitors of, 329 initiation, 317–322 208f
chemoprevention, 220–222, 221f invasive, therapeutic strategies for, 322–330 summary of risk factors for, 218
chemoprevention risk-reduction trials in, invasive breast cancer, in women with atypical surgery, quality measures and outcomes for,
222–225, 222t hyperplasia, 227–228, 227f 499–513
chemotherapy for, 324–327 ionizing radiation in, 217–218 surgical treatment of, 323–324
classifications of mutations in, 285f lobular carcinoma in Situ and atypical survivorship, 1049–1056
clinical perspective on carcinogenesis and hyperplasia, 209 cancer risk and management strategies and,
progression of, 288–289 male, 974–980 1054–1055, 1054b
clinical risk counseling, 220, 220f mammographic density in, 216, 220 cardiac dysfunction and, 1051–1052
clinically established prognostic factors in, medical treatment of, 324–330 care, development of, 1055
250–257, 251b metastases, relationship between primary tumor cognition in, 1050–1051
common mechanisms of, 282 and, 320 fatigue and, 1049–1050, 1050b
common somatic mutations in, 299–301 metastatic, 862–863 fertility and, 1053–1054
descriptive epidemiology of, 207 molecular oncology of, 282–307 imaging and, 1055
dietary fat and serum estradiol, 214 molecular profiling of, 289–294 menopause and, 1053–1054
diethylstilbestrol exposure, 215 sporadic, 298–305 psychosocial issues and healthy lifestyle in,
dye-directed sentinel lymphadenectomy for, molecular subtypes of, 293–294, 295f, 321, 321t 1053
604–606 triple-negative, 294 sexual health, body image, and relationship
early, 863–865 most sensitive cell of, 284 issues in, 1052–1053
enabling replicative immortality of, 284 National Comprehensive Cancer Network sustaining proliferative signaling of, 282–283
endocrine therapy for, 290–291, 327–328, recommendations in, 234–236 tamoxifen for, 221
774–775 natural history of, 315–317 taxanes for, 781–782
tamoxifen as, 908–910 neoadjuvant radiation therapy for, 851–852, therapeutic strategies for, 330
endogenous hormones, 214 851b traditional models for, 315–317, 318f, 318t
epidemiology of, 207–218, 315 night-shift work in, 217 traditional risk factors for, 209–211, 209t, 210f
epigenetic alterations, 304–305 node-negative, postmastectomy radiotherapy in, tumor microenvironment of, 305
estrogen metabolism, 214–215 690 tumor promoting inflammation of, 285
evading growth suppressors of, 283–284 normal mammary development and vaccines for, 328–329
family history, 209 carcinogenesis of, 286–289 women at risk for, 219–220
1086 Index

Breast Cancer Chemotherapy Questionnaire (BCQ), Breast cancer therapy (Continued) Breast conservation therapy (BCT) (Continued)
1040 radical mastectomy and recurrence after breast radiotherapy, 644–645, 654–655
Breast Cancer Detection and Demonstration Project conservation therapy risk factors for local recurrence after, 652–653,
(BCDDP), 1067–1068, 1075–1076, 1078 in local recurrence, 424–425, 427f 653t
Breast cancer genes. See BRCA1; BRCA2. survival after, 426f standards for, 649b
Breast Cancer Index (BCI), of endocrine therapy, total mastectomy, and lumpectomy, 424–425, surgical incision placement in, 647, 647f
914–915 426f factors of, 468
Breast Cancer Prevention Trial (BCPT), 222–224 by type of operation and stage distribution, goal of, 463–465
Breast Cancer Prognosis Gene Expression Assay, 425, 427t historical perspective on, 462
262 in type of operation performed, 424f intraoperative evaluation of surgical margins in,
Breast Cancer Risk Assessment tool, 219 by type of treatment and stage distribution, 637–642
Breast cancer risk management 425–426, 428t for invasive breast cancer, 462–476, 693–705
in clinical setting, 1007 in use of radiotherapy, 424f patient selection for, 467–468, 468f
risk reduction options based on level of risk in, trends and patterns of care, 1985 to 2002, randomized trials of, 463f, 463t, 473t
1007 427–430 local recurrence after, 463–467
risk-based screening recommendations in, 1009, in Canada, 430, 433t genomic profiling of, 987
1009b in first-course surgery, all diagnoses, all magnetic resonance imaging for, 468–469
Breast Cancer Risk Models, 219–220 hospitals, all states, 434t–436t margin status and local recurrence after, 638t
Breast cancer setting, chemotherapy in, 774 frequency of surgical procedures mastectomy and, 463t–464t
Breast cancer susceptibility gene(s), 296f by region, 429, 430t operative technique of, 469–472
Breast cancer therapy by stage distribution, 429t closure, 470
history of, 1–19 modified radical mastectomy, and radical evaluation of margins, 470
in ancient civilizations, 1–2 mastectomy, 429, 432f incision, 469, 469f
Babylonian, 1 in partial (segmental) mastectomy, 428t, 432f localization, 469
Chinese, 1 in relative survival of, 431t–432t oncoplastic surgery, 470
in classic Greek period, 1–2 by stage distribution, 427t quadrantectomy, 469
Egyptian, 1, 2f by year of diagnosis, 428t–430t reexcision, 470–472
in Greco-Roman period, 2, 2f–3f trends in selection of mastectomy therapies, 2000 tumor removal, 469, 470f
in eighteenth century, 5–7 to 2016, 430–435 patient selection for, 467–468, 468f, 694–700,
in middle ages, 2–4 in Japan, 433–434, 434f 694t
Arabic, 4 by type of surgery by year of diagnosis, 428t clinical factors in, 694–696
Christian, 2–3, 3f in United States, 422–435 genetic factors in, 696
Jewish, 3–4 Breast Cancer Treatment Outcome Scale (BCTOS), gross multifocal/multicentric disease in, 696
in nineteenth century, 7–12 719 margin status in, 697–698, 698t
American surgery, 8–9, 9f Breast cancer vaccines, 929–930 pathologic factors in, 696–699
European surgery, 7–8 Breast carcinoma patient age in, 695
in Renaissance, 4–5, 5f age, family history, and proliferative disease as risk race in, 696
in twentieth century, 12–18 factors for, 267, 268t–269t tumor size in, 695–696
breast reconstruction in, 17–18, 18t atypical hyperplasia, extent of, 266–267, 267t tumor subtyping in, 698–699
cancer biology in, 18 complex fibroadenoma, 267–269, 270t with radiation therapy, 472–475
chemotherapy in, 16–17 hormone replacement therapy in, women with randomized trials of, 463f, 463t, 474, 693–694,
hormonal therapy in, 15–16, 16f proliferative disease, 271 694t
mammography in, 17 Mayo Clinic studies in, 265, 265f reasons for underutilization of, 462
radiotherapy in, 14–15, 15f Nashville Breast cohort studies in, 264–265 recommendations on, 467
surgery in, 12–14, 13t, 14f radial scar, 271 recurrence after, 986–989, 987f
immunologic approaches to, 924–933 time since biopsy on risk of, effect of, 265f, retrospective analysis of, 463
adoptive T-cell therapy as, 930–931 269–271, 270f survival after, 462–463, 465f
breast cancer vaccines as, 929–930 in women with proliferative breast disease, risk survival and local recurrence in, 694t, 703t
diagnostic role of tumor associated factors for, 264–271 tamoxifen with, 704
autoantibodies in, 926–927, 926t Breast Center and Breast Surgeon Quality treatment factors in, 699–700
immune checkpoint inhibitor therapy as, Measurement Programs, in United States, adjuvant systemic therapy as, 700
931–932 503t radiation boost as, 699–700
immunity in, 924–925 Breast conservation therapy (BCT), 15, 663, surgery as, 699
immuno-prevention of breast cancer as, 778–779. See also Lumpectomy. volume displacement techniques for, 470
932–933 of axilla, 472, 472f without radiation therapy, 703–704
vaccines, 929–930 axillary dissection in, 462 Breast cysts, 88, 88f
immunologic effects of, 928–929, 928t characteristics and management of local failure Breast density
long-term and late effects of, management of, after, 702–703, 703t on mammography, 339–340
1015–1022, 1016t, 1049, 1050b contraindications to, 468b during pregnancy, 340
trends and patterns of care, 1971 to 1984, cosmetic outcome of, 467, 467f Breast development
422–426 for DCIS, 566–567 cancer and, stem cells in, 308–314
in application of systemic chemotherapy, 424f for early breast cancer, 644 in embryology to childhood, 37–44
chronology of the mastectomy for, 423t boomerang incision, 647–648, 647f clinical correlates of, 38
for five-year survival rate by stage, type of mastectomy and, 654–655 accessory axillary breast tissue as, 39f, 41
operation, and type of adjuvant therapy, minimally invasive ablative therapies, 656 amastia as, 41, 42f
422–423, 425t objective of, 646, 648 newborn nipple discharge as, 43
modified radical mastectomy, 422–423, 432f outcome of, 653–656, 654t Poland syndrome as, 41–43
radical mastectomy, 422–423 periareolar incision, 647 polymastia as, 40–41
 Index 1087

Breast development (Continued) Breast pain (Continued) BSE (breast self-examination), 331–332, 332f–333f
polythelia as, 38–40, 39f, 40t pathogenesis and etiology of, 80 in follow-up care, 1014
precocious puberty as, 43–44, 43f pathophysiology of, 80–82 BSI (Brief Symptom Inventory), 1040, 1041t
premature thelarche as, 43, 43f endocrine influences in, 80–81
hormones in, 37–38 nonendocrine influences in, 81–82 C
morphology of, 37 Breast physiology, 37–56 CA (cancer antigen)
regulatory factors and potential genes in, 38 in embryology to childhood, 37–44 15.3, 905–906
in lactation, 53–55 clinical correlates of, 38 27.29, 905–906
clinical correlates of, 55–56 accessory axillary breast tissue as, 39f, 41 Cabanas, Ramon, 604
delayed onset of lactation as, 55 amastia as, 41, 42f Cabergoline, for breast pain, 85
impact on breast cancer risk as, 56 newborn nipple discharge as, 43 Cabrol, Barthélemy, 422
lactational success as, 55–56 Poland syndrome as, 41–43 Caffeine, breast pain and, 81–82
hormones in, 53–55 polymastia as, 40–41 Calcifications
morphology and product of, 53, 54f polythelia as, 38–40, 39f, 40t linear, 347–348, 348f
regulatory factors and potential genes in, precocious puberty as, 43–44, 43f mammography of, 347–350, 348f
55–56 premature thelarche as, 43, 43f benign, 348–349, 348f–349f
in menopause, 56 hormones in, 37–38 dystrophic, 349, 350f
clinical correlates as, 56 morphology of, 37 fibroadenomas, 344f
hormones as, 56 regulatory factors and potential genes in, 38 milk of calcium as, 349, 350f
morphology of, 56 in lactation, 53–55 secretory, 348–349
in pregnancy, 50–53 clinical correlates in, 55–56 vascular, 348, 349f
clinical correlates of, 51–53 delayed onset of lactation as, 55 malignant, 349–350, 351f
hormones in, 51 impact on breast cancer risk as, 56 railroad track, 348, 349f
morphology of, 50–51 lactational success as, 55–56 secretory, 348–349, 349f
in puberty, 44–50 hormones in, 53–55 “popcorn-like,” 344, 344f
clinical correlates of, 47 morphology and product of, 53, 54f railroad track, 348, 349f
adolescent, juvenile, or virginal hypertrophy regulatory factors and potential genes in, regional, 347–348
as, 47–48 55–56 segmental, 347–348, 349f
gynecomastia as, 49–50, 49f in menopause, 56 CALGB (Cancer and Leukemia Group B), 474,
hypogonadotropism as, 50, 50b clinical correlates in, 56 655, 823
tuberous breast deformity as, 48–49, hormones in, 56 on NAC, 729
48f–49f morphology of, 56 trial 9344, 753
hormones in, 44–45 in pregnancy, 50–53 trial 40503, 920–921
menstrual cycle as, 45–46, 47f clinical correlates of, 51–53 Camper, Pieter, 5
morphology of, 44 hormones in, 51 Canada, trends and patterns of care, 1985 to 2002,
regulatory factors and potential genes in, morphology of, 50–51 430, 433t
46–47, 46f in puberty, 44–50 Canadian Strategy for Cancer Control, on emotional
Breast disease, roles of physician and patient in clinical correlates of, 47 distress, 1039
evaluating, 331–336 adolescent, juvenile, or virginal hypertrophy Cancer, node-negative breast, postmastectomy
Breast duct, anatomy of, 59f as, 47–48 radiotherapy in, 690
Breast duct lobular system, 58f gynecomastia as, 49–50, 49f Cancer and Leukemia Group B (CALGB), 474,
Breast edema, 720 hypogonadotropism as, 50, 50b 655, 823
Breast examination tuberous breast deformity as, 48–49, on NAC, 729
clinical, 332–334 48f–49f trial 9344, 753
imaging modalities for, 334–335 hormones in, 44–45 trial 40503, 920–921
invasive diagnostic procedures for, 335–336 menstrual cycle as, 45–46, 47f Cancer biology, history of, 18
self-, 331–332, 332f–333f morphology of, 44 Cancer genetics counselor, role of, 237–239
Breast Imaging Reporting and Data System regulatory factors and potential genes in, Cancer Research Campaign Clinical Trial, 451,
(BI-RADS), 339 46–47, 46f 452f
Breast infection, 717–719 Breast pump, 57, 59f Cancer risk, in contralateral breast, 991–992
Breast International Group (BIG), 1-98 study, 739, Breast reconstruction. See Reconstruction. Cancer stem cell(s) (CSCs), 288, 859
739f–740f, 916 Breast reduction. See Reduction mammaplasty. Cancer stem cell (CSC) hypothesis, 308
Breast Lymph Node (BLN) Assay, 542 Breast self-examination (BSE), 331–332, Cancer survivorship, psychologic distress and, 1043
Breast mass, self-discovered, 1066–1067 332f–333f Cancer therapy
Breast pain, 79–87, 81f in follow-up care, 1014 contraception and, 776, 776t
classification of, 79–80 Breast stem cells. See Stem cell(s). sexuality after, 776
clinical assessment of, 79–80 Breast tissue, 286 Cancer-related fatigue (CRF), 1032, 1033b, 1049
cyclic, 79–80 BreastOncPx, 262 defined by National Comprehensive Cancer
interventions for, 82t BreastPRS, 262 Network (NCCN), 1049
management of, 82–87 Brief Symptom Inventory (BSI), 1040, 1041t management of, 1050b
algorithm for, 87f BRIP1, mutation in, 248–249 Candidiasis, 188
endocrine therapy for, 83–84 British Columbia randomized radiation trial, Capecitabine
nonendocrine therapy for, 84–85 598–599 for metastatic breast cancer, 888t, 889, 890t,
nutritional therapy for, 82–83 Bromocriptine, for breast pain, 84–85 893
for refractory mastalgia, 85–87 Bronchiolitis obliterans organizing pneumonia in elderly, 903
medication causing, 85t (BOOP), due to radiation therapy, 722 lapatinib plus, 899
nomenclature for, 80 Bronchomediastinal trunk, 35 toxicities of, 893–894
noncyclic, 80 Brown, John, 7 Capsular contracture, 989
1088 Index

Carboplatin Cell concentration, 71 Chemotherapy (Continued)

in breast cancer therapy, 928t Cell proliferation, as predictive factor, 256 future of systemic therapy for, 906
for metastatic breast cancer, 888t, 890t, 893 Cell recovery, 71 single-agent, 888–889, 889t–890t
Carcinoembryonic antigen (CEA), 905–906, 1001 CellSearch system, 906 taxanes in, 891–893
Carcinoma for CTC enrichment, 861, 861t with trastuzumab, 891
adenoid cystic, 151, 151f Celsus, Aurelius, 2 vinca alkaloids as, 895
of breast in pregnancy, and lactation, 993–999 Central adiposity, as risk factor, 211 for metastatic disease, with intact breast primary,
infiltrating, 145–155 Central excision technique, 581, 584f 871–872
histologic types of, 147–151 Central group, of axillary lymph nodes neoadjuvant, 781, 821
histopathologic classification of, 147 anatomy of, 30–31, 30f–31f with breast conserving surgery, 727
molecular classification of, 145–147, 146f, 146t of axillary nodal groups, 390–391, 391f followed by resection or radiation, 729
predictive profiles in, 154–155 in lymphedema, 517, 518f locoregional recurrence risk on NSABP trials
prognosis of, 151–154 Central nervous system (CNS) metastasis(es), in of, 731, 732t, 733f–735f
prognostic profiles in, 154 breast cancer, 942–960 mastectomy and, 730
inflammatory, 154, 154f anticonvulsants for, 947 postmastectomy radiotherapy, 690–691
invasive and in situ, primary tumor characteristics, chemotherapy for, 952–955, 953b, 953t rationale for use of, 727
histologic grading as, 534 clinical presentation of, 943–944 during pregnancy, 996–997
invasive cribriform, 149, 149f corticosteroids for, 946–947 trends and patterns of care, 1971 to 1984,
invasive lobular, 147, 148f diagnostic evaluation of, 944–945 422–423, 424f
invasive mammary, 147, 148f methods of spread and distribution, 943 Chemotherapy as Adjuvant for LOcally Recurrent
of the lung, gynecomastia and, 107 prognosis of, 946 breast cancer trial (CALOR), 808
medullary, 150, 150f radiation sensitizers, 955 Chemotherapy-induced amenorrhea, in early-stage
metaplastic, 151, 152f risk factors for, 942–943 breast cancer, 757
micropapillary, 150, 150f stereotactic radiosurgery for, 950–952 Chemotherapy-induced menopause, 1052
mucinous, 149, 149f surgery for, 949–950 Chemotherapy-induced peripheral neuropathy,
mucoepidermoid, 151 surgical intervention for single, 949–950 1035–1036
salivary gland-type, 150 treatment of, 945–960 diagnosis of, 1036
secretory, 150 Centrally located lesions, 386 treatment of, 1036, 1036t
squamous cell, 151, 153f Centrifugal model, for breast cancer, 315–316 Chemotherapy-related amenorrhea (CRA), 1017
tubular, 148–149, 149f Cephalic vein, anatomy of, 25–26 Cheselden, William, 6
Carcinoma in situ. See Ductal carcinoma in situ; Cephalomedial lymph nodal group, 390–391, 391f Chest radiography
Lobular carcinoma in situ. Cervicoaxillary canal, anatomy of, 26 of lung metastases, 935–936
Cardiac avoidance, in breast radiotherapy planning CHEK2, mutation in, 248 during pregnancy, 994
deep inspiration breathing techniques for, 668 Chemoprevention, 219–222, 221f Chest wall, anatomy of, 20–36
heart blocks for, 668 of invasive breast cancer, 557–558 Chest wall closure
patient positioning for, 668 risks and benefits of tamoxifen for, 228, 228f algorithm for, 799–801, 800f
role of surgeon for, 667, 667f Chemoprevention risk-reduction trials, 222–225, cutaneous and local flaps for, 797
Cardiac complications, 722–724 222t external oblique flap for, 795–796
Cardiac disease, in breast cancer survivors, Breast Cancer Prevention Trial, 222–224 fasciocutaneous flaps for, 796–797
1020–1021 International Breast Cancer Intervention Study I, full-thickness defects of, prosthetic materials and,
Cardiac dysfunction, in breast cancer survivors, 224–225, 224f 798
1051–1052 outcomes in, 223 latissimus dorsi musculocutaneous flap for,
Cardiopulmonary fitness, in rehabilitation, 1032 SERM Chemoprevention Trials, summary of, 790–791, 790f
Cardiovascular disease (CVD) 225, 226t microvascular composite tissue transplantation for,
in adjuvant endocrine therapy, 749–750 unfavorable outcomes in, 223–224, 223f 794
in breast cancer patient, 1028–1029, 1030b Chemotherapy myocutaneous flaps for, 790–791
Cardiovascular system, in rehabilitation, 1031–1032 adjuvant, 729 omental flaps for, 797–798
Carpal tunnel syndrome (CTS), 1034–1035 amenorrhea, ovarian dysfunction, and infertility options for, 789–798
Case-control study design, of clinical trial, 365, 366f due to, 1017 pectoralis major flap for, 794–795
Catecholamines, breast pain and, 81–82 anti-angiogenic therapy to, 823 radiotherapy and reconstruction for, 798–799
Cathepsin D, as biological markers, 537–538 for brain metastases, 805 rectus abdominis transposition and free flaps for,
Catheter drainage, of mastectomy wound, 492 cognitive impairment due to, 1019 791, 791f
Cavity shave margin technique, 639, 639t–640t consideration in, 755–756 resection revisited, full-thickness, 787–788
CBC. See Contralateral breast cancer. for contralateral breast cancer, 970 skin grafts for, 790, 790f
CC (craniocaudal) view, of screening mammography, doxorubicin/cyclophosphamide-based, 691 transverse rectus abdominis myocutaneous flap
337, 338f–339f history of, 16–17 for, 792–794, 792f–793f
CCC (Columbia Clinical Classification), for staging, for locally advanced breast cancer, randomized vertical rectus abdominis myocutaneous flap for,
543, 544t clinical trials of, 821, 821t, 825t 791
CD8+ T-cell, 924 for metastatic breast cancer, 885–906, 903t Chest wall pain, 80
CD44+CD24-flow phenotype, in cancer stem cells, alkylating agents in, 893 Chest wall recurrences, 809
859 anthracyclines in, 890–891 isolated, 984
CD326, in circulating tumor cells, 861 antimetabolites in, 893–894 Childhood, breast development in, 37–44
CDH1, mutation in, 248 fluoropyrimidines as, 893–894, 894f in embryology to childhood, 37–44
CDK (cyclin-dependent kinase) inhibitors, for gemcitabine as, 894 clinical correlates of, 38
metastatic breast cancer, 900t combination, 888–889, 889t–890t accessory axillary breast tissue as, 39f, 41
CDP (complete decongestive therapy), for in elderly, 902–903 amastia as, 41, 42f
lymphedema, 525 epothilones as, 894 newborn nipple discharge as, 43
CEA (carcinoembryonic antigen), 905–906, 1001 first-line regimen of, 888 Poland syndrome as, 41–43
 Index 1089

Childhood, breast development in (Continued) Clinical trial(s) (Continued) Complete randomization, 372
polymastia as, 40–41 phase II, design for, 367–369 Complex fibroadenoma, 89
polythelia as, 38–40, 39f, 40t Fei and Shyr’s balanced, 369, 369t–371t proliferative breast disease and, 267–269, 270t
precocious puberty as, 43–44, 43f Fleming’s, 368, 368t Complex sclerosing lesions, 90, 123–124
hormones in, 37–38 Gehan’s, 367–368 Composite International Diagnostic Interview
morphology of, 37 Simon’s minimax, 368, 369t–371t (CIDI), 86
regulatory factors and potential genes in, 38 Simon’s optimal, 368, 369t–371t Comprehensive Geriatric Assessment, 902
Chimeric antigen receptor (CAR) T-cell therapy, phase III, design for, 369–371 Compression device, in mammography, 337
930 crossover, 369–370, 370f Computed tomography (CT)
Chirurgia Magna, 3 factorial, 370–371, 371f for axillary metastasis of unknown primary,
Chronic renal failure, gynecomastia due to, 109 parallel, 369, 369f 1000
Chronic subareolar abscess, 96–98 phase IV (postregistration), 367 of pleural metastases, 935–936, 936f
causes of, 96–97, 97f randomization process in, 371–372 Connective tissue disorders, 190–191, 191f
factors of, 97 reporting of adverse events for, 375–376 Continual reassessment method, for phase I trials,
presentation of, 96–97, 96f sample size determination and power analysis in, 367, 367f
surgical management of, 97–98, 100f–101f 372–373 Contralateral breast, 981–992
treatment plan for, 97 types of, 364–367 cancer risk in, 991–992
CIBER-SORT (leukocyte gene matrix LM22), case-control study design, 365–366, 366f Contralateral breast cancer (CBC), 967
329 cohort, 364–365 chemotherapy for, 970
Circulating tumor cells (CTCs) controlled, 362, 366–367 cumulative 10-year risk of, 968t, 969f
as biological markers, 537 cross-sectional study design, 365, 365f declining incidence of, 971
cancer stem cells in, 859 interventional, 366 hazard ratio for, 971
clinical applications of, 862–865, 864t uncontrolled, 362, 366 magnetic resonance imaging and, 970, 970t
detection of, 862 Clodronate, for bone metastases, 881, 881t metachronous, 970t
AdnaTest (AdnaGen) for, 861t, 862 Clomiphene, history of, 907 mortality after, 972f
CTCscope for, 861t, 862 Clonal evolution model, 298 temporal trends in, 971f
nucleic acid-based strategies for, 862 Clonidine, 1026 Contralateral prophylactic mastectomy (CPM),
protein-based strategies for, 862 c-myc oncogene, 284 453–455, 972–973
enrichment, 860–862, 861t CNB. see Core needle biopsy. Contrast-enhanced breast MRI, 335
biological properties for, 860–862 CNS metastasis. See Central nervous system (CNS) Controlled trials, 362, 366–367
CellSearch system for, 861, 861t metastasis(es). Cooper, Astley, 8, 8f, 907
CTC-chip technology for, 861–862 Code of Hammurabi, 1 Cooper ligaments, 20, 22f
density gradient separation for, 860, 861t Coefficient of growth rate, 1077 Copenhagen trial, 450
filtration for, 860 Cognition, in breast cancer survivorship, Copy number alterations, 301–304
MagSweeper (Illumina) for, 861–862 1050–1051 Core biopsy, 335–336
physical properties for, 860 Cognitive behavioral therapy, 1045 Core needle biopsy (CNB), 379–382, 380t
as “liquid biopsy,” 865–866 Cognitive dysfunction imaging-guided, 357–358, 358f
methods for analysis of, 859–862, 860f screening of, 1038 Cornil, Victor, 8
Circulating tumor DNA, 306 treatment of, 1038 Corpus Hippocraticum, 1
Circulus venosus, 28–29 Cognitive impairment, due to chemotherapy, 1019 Cortical ovarian tissue, 775
Circumferential measurements, for lymphedema, Cognitive rehabilitation, in breast cancer Cosmesis, breast-related symptoms and, 719–721,
523 survivorship, 1051 719t
Circumscribed margins, 341, 343f Cohort trials, 364–365 Costocoracoid fascia, 27
Cirrhosis, gynecomastia due to, 975 Collaborative Attempt to Lower Lumpectomy Costocoracoid membrane, 27f, 28
Cisplatin Reoperation Rates (CALLER), 467 Coumadin necrosis, 189
in breast cancer therapy, 928t Collaborative Trials in Neoadjuvant Breast Cancer Coumarin (Venalot), for lymphedema, 526
for metastatic breast cancer, 888t, 890t, 893 (CTNeoBC), 814 Council of Rheims, 3
Clamshell technique, 581, 582f Collagen vascular disease, complications in patients Counseling
Classic Greek period, history of breast cancer with, 724–725 genetic risk, 1007
therapy in, 1–2 Collagenous spherulosis, 133f risk management in clinical setting, 1007
Claus model, 1005–1006 College of American Pathologists (CAP), 199, 200f risk reduction options based on level of risk,
Clear cell hidradenoma, 184 Colloid carcinoma 1007
CLEOPATRA trial, 292–293, 766 mammography of, 346, 346f nongenetic risk, 1006–1007, 1006b
Clinical breast examination, 332–334 prognosis for, 255 in psychosocial intervention, 1046
Clinical management, of patient at increased/high Colostrum, 23 Counselor, cancer genetics, role of, 237–239
risk, 1004–1010 Columbia Clinical Classification (CCC), for staging, Couples therapy, family and, 1045
Clinical trial(s) 543, 544t Cowden disease, 47–48
conduct of, 362–376 Columnar cell lesions, 128–129, 129f Cowden syndrome, 239, 976
defined, 362 Comedo, 134 CRA (chemotherapy-related amenorrhea), 1017
design of, 364 Comedo adenoma, 134 Craniocaudal (CC) view, of screening
history of, 362–363 Commission on Cancer (CoC), 500 mammography, 337, 338f–339f
level of evidence of, 375, 375t Common Terminology Criteria for Adverse Events CRICO Strategies, 1058
monitoring response variables in, 373–375, (CTCAE), 521, 522t, 523 Cross-cutting, 505
373t–374t Complementary and alternative methods, for Crossover design, for phase III clinical trials,
phase I, design for, 367 vasomotor symptoms of menopausal women, 369–370, 370f
continual reassessment method for, 367, 1026–1027 Cross-sectional study design, of clinical trials, 365,
367f Complete decongestive therapy (CDP), for 365f
3 + 3, 367, 367f, 367t lymphedema, 525 Cryoablation, 657–659, 658f
1090 Index

Cryo-assisted excision, for nonpalpable tumors, Delayed diagnosis (Continued) Dermatophytosis, 188, 188f
646 miscellaneous, 1071 Dermatosis(es)
CSCs. See Cancer stem cell(s). patient-associated, 1061–1062 inflammatory conditions and
CT. See Computed tomography. physician-associated, 1062–1071 involving dermis, 180–181
CTC(s). See Circulating tumor cells. diagnostic workups requested by physicians involving subcutaneous tissue, 181–182
CTCAE (Common Terminology Criteria for and, 1064 of nipple and breast, 179–180
Adverse Events), 521, 522t, 523 intervals of, 1062–1063, 1063f Dermopathy, body modification-associated, 191
CTC-chip, 861–862, 861t specialty training and, 1063–1064, 1064f DES (diethylstilbestrol), 907
CTCscope, in CTC, 861t of pregnancy-associated (gestational) breast cancer, Descriptive models, to biologically informed
CTL(s) (cytotoxic T lymphocytes), 924 1069–1070 carcinogenesis, 317–322
CTLA-4 (cytotoxic t-lymphocyte-associated protein prevention of, 1079–1080 d’Etiolles, Jean-Jacques-Joseph Leroy, 8
4), 329, 931 self-discovered breast mass and, 1064–1067 Development
Cullen, I., 12 survival and, 1071–1079 embryologic, of breast, 20
Curie, Marie, 14–15 studies showing an adverse effect of, in embryology to childhood, 37–44
Curie, Pierre, 14–15 1071–1075 clinical correlates of, 38
Cushing syndrome, 47 studies showing no effect of, 1075–1079 accessory axillary breast tissue as, 39f, 41
CVD (cardiovascular disease) triad of error for, 1064–1069, 1065f amastia as, 41, 42f
in adjuvant endocrine therapy, 749–750 young age and, 1065–1066, 1065f newborn nipple discharge as, 43
in breast cancer patient, 1028–1029, 1030b Delayed immediate reconstruction, 789 Poland syndrome as, 41–43
Cyclin-dependent kinase (CDK) inhibitors, for Delayed postmastectomy reconstruction, factors polymastia in, 40–41
metastatic breast cancer, 900t influencing, 417–421 polythelia as, 38–40, 39f, 40t
Cyclins D, 141 Delphi process, 507–508 precocious puberty as, 43–44, 43f
Cyclooxygenase 2 (COX2), 932 Deltopectoral lymph nodes, 30, 30f premature thelarche as, 43, 43f
Cyclophosphamide, 324 Dendritic cells, 932–933 hormones in, 37–38
in breast cancer therapy, 928t Denosumab, 882–883 morphology of, 37
for metastatic breast cancer, 888t, 893 Density regulatory factors and potential genes in, 38
Cyst(s), oil, mammography of, 344, 345f breast (See Breast density) in lactation, 53–55
Cytochrome P450 (CYP2D6) alleles, 748 of mass, 341, 343f clinical correlates in, 55–56
Cytochrome P450 (CYP) enzyme 2D6, 230 Density gradient separation, in CTC enrichment, delayed onset of lactation as, 55
Cytologic evaluation, of nipple discharge, 71–72 860 impact on breast cancer risk as, 56
results of, 72t Department of Defense Multicenter Trial of Breast lactational success as, 55–56
sample collection for, 71 Lymphatic Mapping, 609–610 hormones in, 53–55
sample preparation for, 71 Depression, in breast cancer patient, 1027–1028, morphology and product of, 53, 54f
Cytopathology, fine-needle aspiration biopsy in, 1027b regulatory factors and potential genes in,
378 Dermatofibrosarcoma protuberans (DFSP), 194 55–56
Cytotoxic T lymphocytes (CTLs), 924 Dermatologic disorder(s), of breast in menopause, 56
Cytotoxic t-lymphocyte-associated protein 4 congenital and developmental, 177–179 clinical correlates in, 56
(CTLA-4), 931 amastia and athelia, 177 hormones in, 56
gynecomastia, 178–179 morphology of, 56
D hyperplasias, hamartomas and associated in pregnancy, 50–53
Danazol, for breast pain, 84 conditions, 178, 178f clinical correlates of, 51–53
Danish Breast Cancer Cooperative Group, on hypoplasia and associated conditions, 177–178 hormones in, 51
pregnancy after breast cancer, 1017–1018 neoplastic morphology of, 50–51
Danish Breast Cancer Group (DBCG), in IMN RT benign in puberty, 38, 44–50
versus no IMN RT, 679 cysts and adnexal tumors, 183–184, 183f clinical correlates of, 47
Darier disease, 190 erosive adenomatosis of nipple, 184–185, adolescent, juvenile, or virginal hypertrophy
Databases, for quality and clinical outcomes 184f as, 47–48
research, 501–502 lichen planus-like keratosis, 183 gynecomastia as, 49–50, 49f
DCIS. See Ductal carcinoma in situ. seborrheic keratosis, 183 hypogonadotropism as, 50, 50b
De Humani Corporis Fabrica Libri Septem, 4 malignant tuberous breast deformity as, 48–49,
De Medicina, 2 adnexal tumors, 187, 187f 48f–49f
Deep and superficial inferior epigastric artery angiosarcoma, 186–187, 186f hormones in, 44–45
perforator flaps (DIEP), 794 atypical vascular lesion, 186 menstrual cycle as, 45–46, 47f
Deep inferior epigastric perforator (DIEP) flap, inflammatory breast carcinoma, 186, morphology of, 44
484–485 186f regulatory factors and potential genes in,
Deep inspiration breathing techniques, 668, Paget disease, 185–186, 185f 46–47, 46f
668f primary, 177–187 DFSP (dermatofibrosarcoma protuberans), 194
Deep venous thrombosis (DVT), after mastectomy, inflammatory, 179–183 Diagnosis, delayed, 1057–1080
497–498 neoplastic, 183–187 clinical scenarios leading to, 1064–1069
Delayed diagnosis, 1057–1080 benign, 183–185 definition of, 1061
clinical scenarios leading to, 1064–1069 malignant, 185–187 due to false-negative fine-needle aspiration biopsy,
definition of, 1061 secondary, 188–195 1070–1071
due to false-negative fine-needle aspiration biopsy, inflammatory, 188–191 due to false-negative mammogram, 1067–1069
1070–1071 infectious, 188 magnitude of problem of, 1058–1061, 1058b,
due to false-negative mammogram, 1067–1069 noninfectious benign lesions, 188–191 1059t, 1060f
magnitude of problem of, 1058–1061, 1058b, neoplastic, 191–195 of male breast cancer, 1070
1059t, 1060f benign, 191–192 miscellaneous, 1071
of male breast cancer, 1070 malignant, 192–195 patient-associated, 1061–1062
 Index 1091

Diagnosis, delayed (Continued) Docetaxel (Taxotere) Ductal carcinoma in situ (DCIS) (Continued)
physician-associated, 1062–1071 for locally advanced breast cancer, 823 predicting local recurrence, in conservatively
diagnostic workups requested by physicians for metastatic breast cancer, 888t, 889, 890t, treated patients with, 570–573
and, 1064 891 prospective randomized trials for, 568–569
intervals of, 1062–1063, 1063f Doctors Company, 1058 sentinel node biopsy for, 574
specialty training and, 1063–1064, 1064f Dodds, Edward, 15–16, 907 tamoxifen for, 569
of pregnancy-associated (gestational) breast cancer, Dominant lesion, 550.e1 treatment end points for patients with, 566
1069–1070 Donabedian Trilogy, 500 treatment options, 566–568
prevention of, 1079–1080 Dormancy phase, 319 treatment selection for patients with, of breast
self-discovered breast mass and, Dose, maximum tolerated, 366–367, 367f using the University of Southern
1064–1067 Dose density, in first-generation regimens, 754 California/Van Nuys Prognostic Index,
survival and, 1071–1079 Dose-dense chemotherapy, 847–848 570–573, 570t
studies showing an adverse effect of, Dose-limiting toxicity (DLT), 367, 367f, 367t discussion of, 572–573
1071–1075 Dose-response curve, 367, 367f pathologic evaluation in, 570–571
studies showing no effect of, 1075–1079 Doxorubicin (Adriamycin) for patients undergoing mastectomy, 573,
triad of error for, 1064–1069, 1065f in breast cancer therapy, 928t 573f, 573t
young age and, 1065–1066, 1065f early trials of, 780 results, 571–572, 571f–572f, 572t
Diagnostic errors for metastatic breast cancer, 888t, 890t, 891 statistical analysis of, 571
in breast disease, 1079 Drainage catheter, 441–442 breast conserving therapy (BCT) for, 135
safety in surgery and, 500–501 Driver alterations, in carcinogenesis, 299, 300f cellular necrosis in, 134f
Diagnostic mammography, 337–339, 341f Drug Efficacy Study (DES), 363 classification of, 134b, 135t, 137–138
spot compression views in, 337–339 Drug hypersensitivity reactions, 189 comedo type of, 130–131, 131f, 134f–137f
for women 30 years of age, 339 DT (distress thermometer), 1040, 1041t cribriform type of, 130–131, 131f, 133f, 136f
Diaphragmatic lymph nodes, 34 Dual bright-field in situ hybridization, reporting distribution of, 139
Diclofenac, for breast pain, 85 recommendation for, 203t “endocrine” pattern of, 137f
DIEP (deep inferior epigastric perforator) flap, Duct ectasia, 88, 124, 124f excision alone for, 673
484–485 nipple discharge due to, 65t extensiveness, multicentricity, and multifocality of,
Diet, 47 Duct excision 138–139
in breast cancer and lifestyle factors, 1045 technical modifications for, 73–75 extent of disease in, 138
Dietary fat and serum estradiol, breast cancer and, technique of, 72–73, 73f factors associated with local recurrence of,
214 wire localization in, 74f 673–674
Diethylstilbestrol (DES), 907 Ductal adenoma, 128, 128f biological markers and, 674
Diethylstilbestrol exposure, breast cancer and, Ductal carcinoma, invasive, 550.e1f clinical factors in, 673–674
215 Ductal carcinoma in situ (DCIS), 70f, 130–144, histologic subtype and, 674
Digital breast tomosynthesis (DBT), 335, 379 466, 912–913 imaging factors in, 674
Digital mammography, 337 adjuvant endocrine therapy for, 748–749 margin status and, 674
Digitally reconstructed radiograph (DRR), of breast, 562–575 pathologic factors in, 674
681f biopsy techniques for, 565–566 patient factors in, 673–674
Direct smear, 379 breast conservation for, 566–567 tumor size in, 674
Disease-free survival (DFS), 802 changing nature of, 563 flat epithelial atypia of, 130–131, 131f–132f
tumor grade and, 534, 534f classification of, 563–564, 564f intermediate-grade, 136f
Disease-free survival rates, for modified radical detection and diagnosis of, 565–566, 565f mammographic correlation of, 139
mastectomy, 447t, 452f, 454f excision for, reasons to consider, 567–568 mammography of, 350–351, 352f
Dissection, of pectoralis minor, 458 anatomic, 568 margin status of, 139–140
Distant metastases. See Metastatic breast cancer. biological, 568 with microinvasion, sentinel lymph node
Distant relapse, detection of, 1014–1015 common use, 567–568 dissection for, 612–613, 613t
Distress increased risk, 568 micropapillary type of, 130–131, 131f
in breast cancer, 1039–1045 NCCN guidelines, 568 Paget disease with underlying, 174
hereditary, 1041–1042 only one time, 568 pathology of, 133–137, 133f–134f
incidence of, 1039 pathology errors, 568 radiotherapy and, 671–676
screening for, 1040–1041, 1040f, 1041t patient selection, 568 after mastectomy, 676
sources of, 1041–1043 prospective randomized data, 568 recurrence and results of salvage treatment in,
in breast cancer survivors, 1019–1020 radiotherapy may cause harm, 568 675–676
in cancer survivorship, 1043 socioeconomic, 568 tamoxifen and, 674–675, 675t
due to adjuvant therapy, 1042–1043 HER2/neu status and potential benefit of technique for, 675
due to breast biopsy, 1042 neoadjuvant trastuzumab, determination randomized trials on, 671–673, 672t
due to diagnostic process, 1042 of, 569–570 receptor proteins, oncogenes, tumor suppressor
due to surgery, 1042 immunohistochemical and molecular genes, and ploidy of, 140–142, 141f
Distress thermometer (DT), 1040, 1041t phenotypes in, 564 risks of evolution and recurrence from, 140
Distribution, for DCIS, 139 intraoperative radiation therapy for, 567 solid type of, 130–131, 131f
Diuretics invasive breast cancer, progression to, 564 special types of, 142
for lymphedema, 524 mastectomy for, 566 subclassification of, 137t
for mastalgia, 86 microinvasion, 564 surgical margin status in, 637
DL. See Ductal lavage. multicentricity and multifocality of, tamoxifen for, 910
DLT (dose-limiting toxicity), 367, 367f, 367t 564–565 tools to predict risk on, 674
DNA, circulating tumor, 306 oncotype DX breast DCIS score, 573–574 unique biology of, 130–133
DNA markers, as predictive factor, 256 overtreating, 567 Ductal growth phase, 44, 45f
DNA-binding domain (DBD), 274–275 pathology of, 563–565 Ductal hyperplasia, atypical, 91
1092 Index

Ductal lavage (DL), 61–64, 61f Eczematous dermatitis (nummular eczema), 179, Epidemiology, of breast cancer, 207–218
diagnostic categories in, 61–62 179b, 179f Epidermal growth factor receptor (EGFR), 763
of intraductal papilloma, 63f Edinburgh Royal Infirmary—Cardiff trial, as predictive factor, 256
limitations of, 62–63 450t–451t Epidermotropic theory, of Paget disease, 169
molecular markers and, 63–64 survival of all patients in, 451f Epidural spinal cord compression (ESCC), 805,
procedure for, 61–62 Efaproxiral, 955 943–945
Ductal lavage fluid, 57 Effector cells, 924–925 corticosteroids for, 958–959
Ductectomy, for periductal abscess/chronic Egan, R., 17 myelography for, 945, 946f
subareolar abscess, 98f–99f Ehrlich, Paul, 16 prognosis of, 958
Ductograms, 69, 69f–70f, 75f EIC. See Extensive intraductal component. radiation for, 959
Ductography, 68–69, 357 Eighteenth century, history of breast cancer therapy recurrence, 960
Ductoscopy, 69–71 in, 5–7 surgery for, 959–960
Ductules, 44 Elderly patient, metastatic breast cancer in, 902–903 toxicity, 960
Dutch Bone Metastasis Study Group, 879 Electrocautery, 387–388, 411f treatment of, 958–960
DVT (deep venous thrombosis), after mastectomy, Elimination, immunoediting, 319 treatment technique and dose schedule for, 959
497–498 ELLIOT trial, 475 Epigenetic alterations, 304–305
DX Breast DCIS Score (DCIS Score), 141–142 Embryologic development, of breast, 20 Epirubicin, for metastatic breast cancer, 890–891,
Dyspnea EMILIA trial, 954 890t
due to pleural metastases, 934, 935b Emotional distress. See Distress. Epithelial cadherin (E-cadherin), 197, 205, 206f
in pericardial effusion, 961–962 EMT. See Epithelial-mesenchymal transition. Epithelial hyperplasia, 118–119, 119b, 119f–120f
Endocrine chemoprevention, for LCIS, 557–558 of pregnancy, 89b, 92
E Endocrine therapy, 327–328, 783, 817–818 Epithelial immunoSPOT (EPISPOT) assay, in CTC,
E75 vaccine, 930 aromatase inhibitors for, 910–911 861t, 862
Eakins, Thomas, 9 side effects of, 911 Epithelial proliferative lesions, of breast, 143
Early breast cancer, 643 for breast cancer, 907–923, 909t Epithelial-mesenchymal transition (EMT), 284,
adjuvant radiotherapy for, 652–653, 652t for breast pain, 83–84 311–312
axillary evaluation of, 649–652 ductal carcinoma in situ in, 912–913 Epitomae Medicae Libri Septem, 3
cryoablation for, 657–659, 658f for ER- and/or PR-positive breast cancer, EPO (evening primrose oil), for breast pain, 83
family history of, 645–646, 655–656 915–919 Epothilones, for metastatic breast cancer, 894
high-intensity focused ultrasound ablation for, extended duration of, 917–919 Equilibrium, immunoediting, 319
660–661 first-line therapy in, 919–921, 919t ER(s). see Estrogen receptor(s).
interstitial laser therapy for, 659 general strategies for, 908 ERα. See Estrogen receptor α.
invasive lobular, 655 history of, 907–908 ERβ (estrogen receptor β), 274
mammography for, 643 for metastatic breast cancer, tamoxifen as, 908 ligand-binding domain (LBD) of, 275–276
management of the elderly patient with, 653–655, neoadjuvant, for HR-positive breast cancer, 919 ErbB tyrosine kinase inhibitors, for metastatic breast
655t objective of, 290–291 cancer, 900t
mastectomy for, 649 predictive tools for, 913–915 erbB2 (avian erythroblastosis oncogene B2), 283
microwave ablation for, 659–661 selective estrogen receptor downregulators for, Eribulin, for metastatic breast cancer, 888t, 890t
minimally invasive ablative therapies for, 656 911–912 ER-positive disease, 755–758
nonpalpable, 646 selective estrogen receptor modulators for, chemotherapy for, 756
in older women, 655 908–910 Erythrasma, 188, 188f
options for, 644–646, 645t raloxifene as, 910 Escape, immunoediting, 319
preoperative evaluation for, 644 tamoxifen as, 908–910 ESCC. See Epidural spinal cord compression.
radiofrequency ablation for, 656–657, 656f, 657t efficacy of, 908 Essential fatty acids, 47
sentinel lymphadenectomy for, 651–652 metabolism of, 909–910 Established criteria of the Union Internationale
spectrum model of, 643 side effects of, 908–909 Contre le Cancer, 787
surgical management of, 643–662 toremifene as, 910 Estradiol, estrogens and, 286
Early Breast Cancer Trialists’ Collaborative Group Endocrine-sensitive metastatic breast cancer, 888f Estrogen(s)
(EBCTCG), 250, 323–324, 462, 599, 600f, Endogenous HER2-specific antibodies, 925 breast pain and, 81
678 Endogenous hormones in endocrine therapy, 910
Early follicular phase, in menstrual cycle, 45, 47f breast cancer and, 214 in regulation of mammary gland, 23–24
Early invasive breast cancer, 643 growth factors and, 286–288 topical, 1027
Early-stage breast cancer Endometrial carcinoma, tamoxifen and, 909 for vulvovaginal atrophy, alternatives to, 1027
adjuvant and neoadjuvant systemic therapies for, EndoPredict test, 262 in tumor microenvironment, 319
752–762 Endothelial growth factor (EGF) receptor family Estrogen action, 276
breast conserving therapy for, 637 signaling, proliferation-inducing pathways in molecular mechanism of, 274–276
patient positioning for, 666–667 breast cancer, 282–283 Estrogen excess, in gynecomastia, 106–108
radiation therapy for, 663 Endothoracic fascia, anatomy of, 24–25, 24f Estrogen metabolism, breast cancer and, 214–215
Eastern Cooperative Oncology Group (ECOG) EORTC (European Organization for Research and Estrogen paradox, 317, 319f
E1199 trial, 753–754 Treatment of Cancer), 137 Estrogen receptor(s) (ERs), 272–280
on ovarian suppression, 744–745 10871 trial, 174 analysis of, 689–690
EBCTCG. See Early Breast Cancer Trialists’ in radiotherapy, 677 function in breast cancer, 921f
Collaborative Group. 22922 trial, 679 historical perspective of, 197–198, 272–274, 274t
E-cadherin (CDH1), 284, 298 EORTC QLQ-C30/+BR23 (European Organization history of, 907
mutation in, 285 for Research and Treatment of Cancer core independent activation, 291f
Ectopic axillary breast tissue, 39f, 41 questionnaire and breast module), 1040 in locally advanced breast cancer, 820
Ectopic human chorionic gonadotropin, EpCAM-based enrichment technologies, in molecular mechanism of, 274–276
gynecomastia and, 107 circulating tumor cells, 861–862 monoclonal antibodies for, 201t
 Index 1093

Estrogen receptor(s) (ERs) (Continued) External oblique flap, 795–796, 797f Fine-needle aspiration biopsy (FNAB), 335–336,
as predictive factors, 250 Extraaxillary nodal recurrences, 809f, 810 377–378, 380t
as primary tumor characteristics, 535 Extramammary malignancies, breast metastases false-negative, 1070–1071
proliferation-inducing pathways in breast cancer, from, imaging of, 347, 347f during pregnancy, 994–995
282–283, 289–291 Extreme oncoplasty, 586–588, 589f random periareolar, 64
status, predictive power of, 908 Extremity elevation, for lymphedema, 524 Fine-needle aspiration cytology (FNAC). See
structure of, 290f Fine-needle aspiration biopsy (FNAB).
tamoxifen and, 272 F First-generation regimens, 753–755
tissues of, proper technique for processing, FA(s). See Fibroadenoma(s). Fisher, Bernard, 15, 15f
387 Fabry, Wilhelm, 4–5, 4f Fisherian thesis, 643
Estrogen receptor α (ERα), 274, 283, 289 Factorial design, for phase III clinical trials, Fistula, 92
ligand-binding domain (LBD) of, 275–276 370–371, 371f Flap(s)
Estrogen receptor β (ERβ), 274 Fair peer comparisons, 508 depiction of skin, 395f
ligand-binding domain (LBD) of, 275–276 False-negative fine-needle aspiration biopsy, design of skin, 395f
“Estrogen window,” 44 1070–1071 dissection of, 402f
Estrogen-based therapy, alternatives to, for False-negative mammogram, 1067–1069 edge of, 413f
management of vasomotor symptoms, False-negative rate, 594 mastectomy site for, 412f
1025–1027 Familial breast cancer, 219. See also Hereditary breast mobilization, 414
antidepressants, 1025–1026, 1026t cancer. skin, elevation of, 402f, 414
clonidine, 1026 Family history, and bilateral breast cancer, 968 thickness of, 393, 414
complementary and alternative methods for, Fas ligand, 284 TRAM (See Transverse rectus abdominis
1026–1027 Fascial relationship, of breast, 28 myocutaneous (TRAM) flap)
gabapentinoids, 1026 Fasciocutaneous flaps, 796–797 Flat epithelial atypia, 91
progesterone analogs, 1026 Fat grafting, reconstruction with, 485–486 Fleisher syndrome, 41f
Estrogen-induced apoptosis, 278–280, 279f Fat necrosis, 92, 124, 181, 181f Fleming’s design, for phase II clinical trial, 368,
European Organization for Research and Treatment Fatigue, 716, 1032–1033, 1032b 368t
of Cancer (EORTC), 137 in breast cancer survivors, 1019, 1049–1050, Florid ductal epithelial hyperplasia, 90
10871 Trial, 174 1050b Florid hyperplasia, 118, 122f
in radiotherapy, 677 FDG-PET (18-fluorodeoxy glucose positron Florid papillomatosis, 65
22922 trial, 679 emission tomography), of pleural metastases, Fluid aspiration, from palpable breast cysts, 379,
European Organization for Research and Treatment 936, 936f 379f
of Cancer core questionnaire and breast module Feasibility, 507 Fluorescent in situ hybridization (FISH), 63, 63f
(EORTC QLQ-C30/+BR23), 1040 Fei and Shyr’s balanced design, for phase II clinical reporting recommendation for, 203t
European Society of Breast Cancer Specialists’ trials, 369, 369t–371t Fluorodeoxyglucose positron emission tomography
(EUSOMA), 509 Female sexuality, after cancer therapy, 776 (FDG-PET), 944
European surgery, in nineteenth century, 7–8 Female steroid hormones, LCIS and, 557 Fluoropyrimidines, for metastatic breast cancer,
Evaluation of Faslodex versus Exemestane Clinical Fertility, in breast cancer survivors, 1053–1054 893–894, 894f
Trial (EFECT), 921–922 Fertility preservation options, 775–776 5-Fluorouracil, 324
Evening primrose oil (EPO), for breast pain, 83 Fetal development. See Embryologic for metastatic breast cancer, 888t, 893, 894f
Evidence-based Network for the Interpretation of development. FNAB. See Fine-needle aspiration biopsy.
Germline Mutant Alleles (ENIGMA), 242 Fibroadenoma(s) (FAs), 89, 89f, 124–129, 125f, FNAC (fine-needle aspiration cytology). See
Examination 156 Fine-needle aspiration biopsy (FNAB).
breast self, 331–332, 332f–333f calcifications in, 344f Follicle stimulating hormone (FSH), in endocrine
clinical breast, 332–334 juvenile, 126 therapy, 737
imaging modalities for, 334–335 mammography of, 344, 344f Follicular phase, 57
invasive diagnostic procedures for, 335–336 Fibroadenomatosis (fibroadenomatoid mastopathy), Follicular phase, in menstrual cycle, 45, 47f
Excisional biopsy, 335–336, 377 89 Follow-up care
Exemestane, for breast cancer, 232 Fibroblast growth factor receptor (FGFR), 283 ASCO and ACS recommendations for,
Exercise FGFR1, 302 1012b–1013b
in breast cancer survivorship, 1052 FGFR2, 302 for cardiac disease, 1020–1021
for lymphedema, 525–526 amplification of, 304 for chemotherapy-related amenorrhea, ovarian
in rehabilitation, 1037 signaling and its role in cancer, 303f dysfunction, and infertility, 1017
Exercise and Nutrition Enhance Recovery and Good Fibroblastic neoplasms, 158–160 for cognitive impairment, 1019
Health for You (EMERGY) trial, 1047 Fibrocystic change, 116 for fatigue, 1019
Extended radical mastectomy, 437 Fibrocystic disease, 80, 116 general considerations for, 1011–1023
Extensive intraductal component (EIC), 466 Fibroepithelial neoplasms, 156–158 for hormonal symptoms and sexual dysfunction,
invasive carcinoma with, 351, 352f fibroadenoma, 156 1018–1019
External beam radiation therapy (XRT), 669. See mammary hamartoma, 158 for lymphedema and other local sequelae,
also Radiation therapy. phyllodes tumor, 156–158, 157f–158f 1015–1016
standard treatment field setup of, 664–666 Fibroglandular tissue pattern, on mammography, managing long-term and late effects of cancer
techniques and considerations of, 664–667 339–340, 342f treatment in, 1015–1022
External beam versus brachytherapy, 663–664 Fibromatosis, 158, 158f for musculoskeletal complaints, 1017
External intercostal membrane, 25, 29f Fibrous gynecomastia, 105–106 non–cancer-related, 1022
External intercostal muscles, 24f, 25 Fibrous neoplasms, 192, 192f for osteoporosis, 1016–1017
External mammary group Ficoll, in CTC enrichment, 860, 861t for pregnancy, 1017–1018
of axillary lymph nodes, anatomy of, 30, Filtration, for CTC enrichment, 860 for psychosocial concerns, 1019–1020
30f–31f “Final Assessment” categories, in mammographic surveillance for locoregional recurrences or new
of axillary nodal groups, 390, 391f report, 339 primary disease in, 1011–1014
1094 Index

Follow-up care (Continued) Genetics, breast cancer (Continued) Gross multifocal/multicentric disease, in breast
survivorship care planning in, 1022 identifying mutation carriers, 238t–240t, conserving surgery and radiation, 696
for thrombosis, 1020 239–240 Group for Cancer Care Evaluation (GIVIO) study,
for treatment-related cancers, 1021–1022 managing cancer in mutation carriers, 246–249 1015
Foreign-body mastitis, 182 syndromes, 246–249 Growth rate, coefficient of, 1077
Forkhead box 3 (FOXP3) expression, 924–925 managing cancer risk, 244–246, 244t Grubbe, Emil, 14–15
Formalin-fixed paraffin-embedded (FFPE), 259, 782 chemoprevention, 245 Gynecomastia, 49–50, 49f, 104–115, 178–179, 975
Fracture enhanced surveillance, 245 in aging male, 114–115
in adjuvant endocrine therapy, 750 reproductive and lifestyle factors, 244–245 associated with prostate cancer therapy, 115
pathologic, in bone metastases, 878 risk reducing surgery, 245–246 breast cancer and, 106
rib, 721 multigene panels, 243–244, 244f clinical presentation of, 104
Frequently altered molecular pathways, 304 syndromes/genes/pathology/counseling/testing/ conditions associated with, 106b
Frozen section analysis (FSA), 640, 640t treatment, 237–249, 238f, 238t drugs associated with, 109–110, 109b–110b, 110t
Fulvestrant, 274f, 276, 911 value of genetic testing, 237 fibrous, 105–106
Fulvestrant and Anastrozole in Combination Trial Genome-wide association studies (GWAS), 976 histopathology of, 105–106
(FACT), 920 Genomic analysis, 325 management of, 110–114
Functional Assessment of Cancer Therapy-Breast Genomic assays, evaluation of male breast enlargement in, 111,
(FACT-B), 1040 for breast cancer, 260t 111f
Future fertility, in breast cancer, 777 prognostic factors of, 258–262 medical, 112
Genomic characterization, 811 surgical, 112–114, 113f–114f
G Genomic Grade Index, 262 treatment of male breast enlargement in,
Gabapentin, 1026 Genomic instability, 285 112–114
Gabapentinoids, 1026 Genomic profiling neonatal, 104
Gadolinium-enhanced magnetic resonance imaging of local recurrence after breast conserving therapy, pathophysiology of, 106–110
(MRI), 944 987 altered androgen-to-estrogen ratio in, 108
Gail model, 219, 1004, 1005b for risk stratification, 755–756 androgen deficiency in, 108–109
Gail risk, elevated, high risk women secondary to, GeparQuatro, 848 drugs in, 109–110, 109b–110b, 110t
1008 Germ cell tumors, gynecomastia and, 107 estrogen excess in
Galactoceles, 191 Gershon-Cohen, Jacob, 17 adrenal cortex neoplasms, 107
mammography of, 344 Geschickter’s diseases, 479f ectopic human chorionic gonadotropin
Galactography, 68–69 Gestational breast cancer. See Pregnancy-associated production in, 107
wire localization and, 74f (gestational) breast cancer. hermaphroditism in, 107–108
Galactorrhea, due to psychotropic drugs, 66 Gestrinone, for breast pain, 84 testicular tumor in, 106–107
Galen, 2 Gigantomastia, of pregnancy, 51 physiology of, 104–105, 105f
Gamma-linolenic acid, for breast pain, 83 Gilman, Alfred, 16 prevalence of, 104
Gap, in quality of care, 501 Giuliano, Armando, 14 pubertal, 105
GEC-ESTRO Breast Cancer Working Group in Glycogenated squamous cells, in Paget disease, in pubertal male, 114
2013, 645–646 171 senile, 105, 106f
Gehan’s design, for phase II clinical trials, 367–368 Gocht, Hermann, 14–15 summary of, 114–115
Gemcitabine Goldberg, S., 15
in breast cancer therapy, 928t Gonadarche, 287–288 H
for metastatic breast cancer, 888t, 890t, 894 Gonadotoxicity, of cancer therapies, in reproductive- Haagensen, Cushman, 13, 13f, 1057–1058, 1079
Gene expression profiling, 691 age women, 774–775 breast disease into nine types by, 1079
of breast cancer cells, 858–859 Gonadotropin-releasing hormone (GnRH), 52f Haddow, Alexander, 15–16, 907
Gene expression profiling platforms (GEPs), in endocrine therapy, 737 Hair disorders, 191
321–322 Graded prognostic assessment (GPA), 946 Halsted, William Stewart, 9–10, 10f, 13, 17, 422
Genentech, 202 Granular cell tumor, 162 Halsted incision, 392f
General Health Questionnaire (GHQ-12), 1041t Granulocyte macrophage colony-stimulating factor Halsted ligament, 28
GeneSearch breast lymph node assay, 542 (GM-CSF), 328 Halsted radical mastectomy, 422–443, 447t. See also
Genetic factors, in breast conserving surgery and Granuloma annulare, 190 Radical mastectomy.
radiation, 696 Granulomatous lobular mastitis, 182 Annual National Cancer Database (NCDB)
Genetic predisposition. See also Familial breast Granulomatous mastitis, idiopathic, 98–103 Benchmark Reports in, 436f
cancer; Hereditary breast cancer. diagnosis of, 99–100, 100b, 102f historical aspects for development of, 422
high risk women secondary to, 1008–1009 etiology of, 100 immediate breast reconstruction with, 442
risk-based screening recommendations in, 1010 imaging of, 99, 101f–102f indication for, 436–437, 437b
Genetic risk counseling, 1007 treatment of, 100–103 for large breast lesions, 438f
risk management in clinical setting, 1007 Gravid hypertrophy, 51 percentage of breast cancers receiving, 433f
risk reduction options based on level of risk, Gray incision, 392f principles of, 422
1007 Greco-Roman period, history of breast cancer technique for, 437–442
Genetic test, 1054, 1054b therapy in, 2, 2f–3f drainage catheter in, 441–442
Genetic testing technology, 240–242 Greenough incision, 392f exposure of the superolateral aspect of, 439f
Genetics, breast cancer Greenspan, E., 16 flap closure in, 441
cancer genetics counselor role in, 237–239 Grisotti technique, 581 immediate breast reconstruction in, 442
classifying variants, 242–243, 242t, 243f Groote Schur trial, 449 incisions in, 438
genetic testing technology, 240–242 Gross, Samuel David, 9, 9f large skin flaps in, 442f
large rearrangements, 241–242 Gross, Samuel W., 9 lateral (axillary) nodal group, swept of, 440
next generation sequencing, 241, 241f Gross intraoperative inspection, of tumor margins, patient positioning in, 437
Sanger sequencing, 240–241 639 position of the first assistant in, 437–438, 438f
 Index 1095

Halsted radical mastectomy (Continued) HER2-positive metastatic breast cancer Hormonal Replacement Therapy after Breast Cancer
prepped, 437–438 brain metastases in, 899 Diagnosis—Is it Safe? (HABITS) trial, 1025
residual margins in, 441f to CNS, 899 Hormonal symptoms, in breast cancer, 1018–1019
split-thickness skin graft in, 442f investigational agents for, 900t Hormonal therapy, 802. See also Endocrine therapy.
superomedial dissection in, 440f trastuzumab for, 895 history of, 15–16, 16f
thoracodorsal nerve in, 440 treatment of, 895–899, 896t with selective estrogen receptor modulators, 258
thoracodorsal neurovascular bundle in, HER2-targeted therapy, 764–767, 765t Hormone assays, 908
440–441 future directions in, 767–768 Hormone receptor, qualitative values for, 387
typical position for draping patient in, 437f Herceptin. See Trastuzumab. Hormone receptor (HR) negativity, 839
Halstedian and alternative hypotheses, comparison Herculaneum, surgical instruments from, 2 Hormone receptor-positive breast cancer
of, 317t Hereditary breast cancer, 1041–1042 biomarkers in, 747–748
Hamartoma(s), 90, 178, 178f Hereditary diffuse gastric cancer (HDGC) disease-free survival of, 745t
of breast, 126 syndrome, 248 Hormone replacement therapy (HRT)
mammography of, 344, 344f Heregulin-α, in Paget disease, 169 increased use of, 315
Handley, R.S., 32 Hermaphroditism, gynecomastia and, 107–108 in women with proliferative disease, 271
Handley, William Sampson, 12, 12f HGF (hepatocytes growth factor), in puberty, 46–47 Hormone therapy. See Hormone replacement
Harper, M.J., 907–908 Hidradenitis suppurativa, 180 therapy.
Harrington, S., 15 High dose/dose intense alkylator-containing Hormones and Physical Exercise (HOPE) study,
Hawthorne effect, 509 therapies, 836–837 1046–1047
Haybittle-Peto procedure, 373 High risk women Horowitz, K., 15–16
Health insurance, 1043 secondary to genetic predisposition, 1008–1009 Hospital Anxiety and Depression Scale (HADS),
Healthy lifestyle, in breast cancer survivors, 1053 risk-based screening recommendations in, 1010 1040, 1041t
Hearing loss, musculoskeletal complaints, 1017 secondary to premalignant lesions and elevated Hot flashes
Heart, “water-bottle” enlargement of, 962 Gail risk, 1008 in breast cancer survivors, 1018
Heart blocks, for cardiac avoidance, 668 prior thoracic radiation at, risk-based screening in menopause in breast cancer patient, 1024
Hedgehog signaling, 309 recommendations, 1009, 1009b HoxB13/IL17BR ratio index, 261–262
Heidelberger, C., 16 High-intensity focused ultrasound (HIFU), 656 HRT. See Hormone replacement therapy.
Heidenhain, Lothar, 8 High-intensity focused ultrasound ablation, H-score, 199
Heister, Lorenz, 6 660–661 HT (hormone therapy). See Hormone replacement
Helper T cells (Th) High-lying lesions, incision for, 396 therapy.
type 1 (Th1) CD4+, 924–925 High-mobility-group box 1 (HMGB1), 928–929 Huang Di, 1
type 2 (Th2) CD4+, 924–925 Hippocrates, 1 Huggins, Charles, 15–16, 16f, 907
Hemangioendothelioma, 160 Histologic factors, as prognostic marker, 254–255 Human epidermal growth factor receptor 2 (HER2),
Hemangioma, 160 Histone acetylation, 304 201–204
Hemangiopericytoma, 159 Histone deacetylase (HDAC) inhibitors, for historical perspective, 201–202
Hematoma-directed ultrasound guidance (HUG), metastatic breast cancer, 900t standard practice and new challenges, 202–204,
469, 646 Histopathologic features, as primary tumor 203t, 204f
Hematoxylin and eosin (H&E) stains, 639 characteristics, 534–535 Human epidermal growth factor receptor-2 (HER2)
Hemibatwing, 581, 581f Histopathologic grade, in staging, 548, 548t receptor signaling
Hemorrhage, after mastectomy, 496–497 History, of breast cancer therapy, 1–19 alteration, 302
Hepatocellular carcinoma, gynecomastia and, 107 in ancient civilizations, 1–2 amplification of, 292, 302
Hepatocyte growth factor (HGF), in puberty, Babylonian, 1 downstream consequences of, 292
46–47 Chinese, 1 proliferation-inducing pathways in breast cancer,
HER2 (human epidermal growth factor receptor 2), in classic Greek period, 1–2 282–283, 292–293
201–204 Egyptian, 1, 2f trastuzumab and, 293f
amplification, in circulating tumor cells, 863 in Greco-Roman period, 2, 2f–3f Human homolog for the avian erythroblastosis
biology of, 763 in eighteenth century, 5–7 oncogene B2 (ERBB2), 302
in locally advanced breast cancer, 820 in middle ages, 2–4 Human placental lactogen (HPL), 51
measurement of, 262 Arabic, 4 Humeral nodes, 516, 518f
overexpression of, as predictive factor, 256 Christian, 2–3, 3f Humoral immune response, 925
pathology of, 763, 764b Jewish, 3–4 Hunter, John, 6, 6f
positivity of, 834, 839 in nineteenth century, 7–12 Hunter, William, 514
variants, role of, 767 American surgery, 8–9, 9f 27-hydroxycholesterol (27-HC), 276
HER2 adjuvant therapy, 766–767 European surgery, 7–8 Hyperbaric oxygen, for lymphedema, 526
HER2 metastatic therapy, 764–766 in Renaissance, 4–5, 5f Hypercalcemia, in bone metastases, 877
HER2 vaccine, 929 in twentieth century, 12–18 Hyperplasia, 178, 178f
HER2-directed therapy, for metastatic breast cancer, breast reconstruction in, 17–18, 18t atypical, 119–121 (See also Atypical hyperplasia)
885–906 cancer biology in, 18 atypical ductal, 118, 121, 122f
HER2-negative breast cancer, chemotherapy for, chemotherapy in, 16–17 atypical lobular, 121, 121f
325–327, 326t hormonal therapy in, 15–16, 16f epithelial, 118–119, 119b, 119f–120f
HER2/neu, overexpression of, in Paget disease, 169 mammography in, 17 florid, 118, 122f
HER2/neu expression, as primary tumor radiotherapy in, 14–15, 15f pseudoangiomatous stromal, 127
characteristics, 535 surgery in, 12–14, 13t, 14f Hypersecretory ductal carcinoma in situ, 142
HER2/neu gene, 569 Hodges, C.V., 907 Hyperthyroidism, gynecomastia and, 108
HER2/neu status, determination of, 569–570 Holthaus, F.J. Jr., 907 Hypertrophy
HER2-positive breast cancer, 763–768 Holzknecht, Guido, 15 adolescent, 92
with brain metastasis, clinical trials for, 955t Home, Everard, 8 juvenile, or virginal, 47–48
HER2-positive disease, 758–759 Hormonal regulation, of mammary gland, 23–24 Hypertrophy, gravid, 51
1096 Index

Hypodermis, 28 Immunologic approaches, to breast cancer therapy, Inframammary excision, 581

Hypofractionation, 668 924–933 “Ink on tumor,” 987–988
Hypogonadotropism, 50, 50b adoptive T-cell therapy as, 930–931 Innate immune response, 924
Hypophysectomy, for breast cancer, history of, breast cancer vaccines as, 929–930 Innermost intercostal muscles, anatomy of, 24f, 25
15–16 immune checkpoint inhibitor therapy as, Innervation
Hypoplasia, associated conditions and, 177–178 931–932 of breast, 29
Hypothyroidism, 43–44, 44f immunity in, 924–925 of pectoral muscles, 388–390, 389f
immuno-prevention of breast cancer as, 932–933 Inoperable LABC, 730
I tumor associated autoantibodies in, diagnostic Intact breast primary, management of, in setting of
Ibandronate, 881, 881t role, 926–927, 926t metastatic disease, 867–875
IBC. See Inflammatory breast cancer. Immunologic effects, of breast cancer therapies, American Society of Clinical Oncology (ASCO)
IBTR. See Ipsilateral breast tumor recurrence. 928–929, 928t in, 872–873
Idiopathic granulomatous mastitis, 98–103, 101f Immunotherapy, 328–330 asymptomatic primary tumors in, 874–875
diagnosis of, 99–100, 100b, 102f for metastatic breast cancer, 900t locoregional therapy in, 874–875
etiology of, 100 In situ carcinomas. See also Ductal carcinoma in nonsurgical group in, 872, 873f–874f
imaging of, 99, 101f–102f situ; Lobular carcinoma in situ. radiotherapy as, 869t
treatment of, 100–103 of breast, 130–144 randomized prospective trials for, 871–874, 871t
IHC4 assay, 262 Incisional biopsy, 377 de novo stage IV breast cancer patients in,
IHC-detected micrometastases, prognostic Incisions 873–874
significance of, 634–635 for axillary dissection, 410f, 414f induction systemic therapy in, 871–872,
Ill-defined margins, 343f general anesthesia for, 411f 873f–874f
Illustrations of the Diseases of the Breast, 8 Gray, 392f locoregional therapy before systemic therapy in,
Image-guided radiation therapy (IGRT), 667 Greenough, 392f 872–873
Imaging Halsted, 392f retrospective analyses of, 868–871
of axillary metastasis of unknown primary, for high-lying lesions, 396 in de novo stage IV breast cancer, 869t, 870
1000–1001, 1002f–1003f Kocher, 392f locoregional control in, 870
of breast, 337 for lower outer quadrants, 395f radiotherapy for, 870
breast cancer survivorship and, 1055 Orr, 392f, 394f–395f selection biases in, 870–871
for breast examination, 334–335 skin, 411f surgical resection of primary tumor and
ductography for, 357, 358f Stewart, 392f, 394f survival in, 868–870, 869f, 869t
for follow-up Induced abortion, breast cancer and, 215–216 Integrins, 305
after mastectomy, 361, 361f Infection, of breast, 717–719 Intensity modulated radiation therapy (IMRT), 717
of conservatively treated breast, 359, Infection prophylaxis, for lymphedema, 524 Intensity-modulated RT/volumetric modulated arc
360f–361f Infectious disorders, 188 therapy (IMRT/VMAT), 680
of women with breast cancer, 359–361, 359f Inferior gluteal artery perforator (IGAP) flaps, 485 Intercostal arteries, 24f, 25
for guided interventional procedures, 356 Infertility, due to chemotherapy, 1017 Intercostal brachial nerve, 29
imaging-guided core needle biopsy as, Infiltrating carcinomas. See also Invasive Intercostal lymph nodes, 34
357–358, 358f carcinoma(s). Intercostal nerves, 24f, 25, 29, 29f
preoperative needle localization as, 359, 359f of the breast, 145–155 Intercostal spaces, 24–25
specimen radiography, 359 histologic types of, 147–151 Intercostal veins, 35f, 36
magnetic resonance, 337, 355–357, 356f histopathologic classification of, 147 Intercostal vessels, 25
standardized terminology for reports on, 356 molecular classification of, 145–147, 146f, 146t Intercostales intimi, 25
typically benign findings on, 356, 357f predictive profiles in, 154–155 Intercostobrachial nerve, 27
mammography for (See Mammography) prognosis of, 151–154 Internal intercostal membrane, 25
for nipple discharge, 334–335 additional elements in, 153f–154f Internal intercostal muscles, 24f, 25
during pregnancy, 994 histologic grading in, 152–153, 152t Internal mammary lymph sentinel node,
in staging, 532 tumor stage in, 151–152 management of, 615
ultrasound, 353–354, 354f–355f prognostic profiles in, 154 Internal mammary nodal disease
of benign masses, 353–354, 355f Infiltrative lobular carcinoma, 550.e1, 550.e1f as prognostic significance, 541–542
of malignant masses, 354, 355f–356f Inflammatory breast cancer (IBC), 154, 154f, in staging, 541–542, 541f
Imaging-guided interventional procedures, 357–359 832–838, 865 Internal mammary nodal group, 31f, 32–33
Imhotep, 1 clinical presentation of, 832–833, 834f Internal mammary node (IMN), radiotherapy for,
Immediate postmastectomy reconstruction, factors definition of, 832 677
affecting, 417–421 diagnosis of, 832–835 Internal mammary (IM) node metastasis, incidence
Immediate Preoperative Anastrozole, Tamoxifen or epidemiology of, 832, 833f of, 983
Combined with Tamoxifen (IMPACT) trial, imaging in, 833–834, 834f–835f Internal mammary vein perforators, 35f, 36
826 medical management and trials of, 835–837 Internal thoracic lymph nodes, 34
Immune checkpoint inhibitor therapy, 931–932 metastatic disease, 838 International Breast Cancer Intervention Study I,
Immune recognition, of breast cancer, 924–925 new direction in, 838 224–225, 224f
Immune-mediated effect of chemotherapy, pathology of, 834–835 International Breast Cancer Study Group (IBCSG),
329–330 postneoadjuvant/adjuvant strategies for, 836–837 599–600, 635, 678, 1017–1018
Immunity, innate and adaptive, 924–925 radiation management of, 837–838 International Prognostic Index (IPI), 167
Immunocytochemistry, in CTC, 861t surgical management of, 837 Interpectoral group, of axillary lymph nodes,
Immunoediting, 319 Inflammatory breast carcinoma, 186, 186f, 727f, 30f–31f, 31
Immunohistochemistry (IHC), 254 730 Interpectoral (Rotter) nodes, 592
for pleural metastases, 937 Inflammatory myofibroblastic tumor (IMT), 159 Interstitial brachytherapy (IBT), 669
reporting recommendation for, 203t Infraclavicular lesions, incision for, 396 Interstitial laser therapy (ILT), 656, 659
Immunohistologic methodologies, 387–388 Infraclavicular lymph node, 30 Interventional trials, 366
 Index 1097

Intracavitary brachytherapy balloon-based Ipsilateral breast tumor recurrence (IBTR) Lactation (Continued)
brachytherapy, 669–670 (Continued) hormones in, 53–55
Intraductal breast biopsy (IDBB), 76 patient age in, 695 morphology and product of, 53, 54f
Intraductal papilloma(s), 65f, 90–91 patient selection for, 694–700 regulatory factors and potential genes in, 55–56
ductal lavage of, 63f race in, 696 mammary glands during, 22–23
ultrasound of, 67–68 treatment factors in, 699–700 sentinel lymph node dissection during, 612
Intraepidermal transformation theory, of Paget adjuvant systemic therapy as, 700 Lactational abscess, 95–96
disease, 169–170 radiation boost as, 699–700 Lactational bloody nipple discharge, 66
Intramammary lymph node(s) (intraMLNs), on surgery as, 699 Lactational mastitis, 95–96
mammography, 344, 345f tumor size in, 695–696 Lactiferous ducts, anatomy of, 21–22, 22f
Intramammary nodal disease tumor subtyping in, 698–699 Lactiferous sinus, 59f
prevalence of, 542 classification of, 1014t anatomy of, 21–22, 22f
staging of, 542 with lumpectomy, 473t Lactogenesis, 53
Intraoperative cytologic evaluation by touch risk of, 693 Lanfranc of Milan, 3
preparation, for margins, 640, 641t Irreversible electroporation, 661 Langer or Kraissl lines, 647, 647f
Intraoperative photon/electron radiotherapy, 670 Irritant contact dermatitis, 180 Lapatinib, 761, 765, 765t, 954
Intraoperative radiation therapy, 712–715, 713t Isolated axillary recurrences, 983 for locally advanced breast cancer, 824
additional studies of, 714 Isolated lung metastases, 803 for metastatic breast cancer, 898
boost of, 714 Isotope filtration, dose and volume of injectate, 622 Late radiation cosmetic effects, risk of, 720
for DCIS, 567 Italian Group for Cancer Care (GIVIO), 1074 Lateral group, of axillary lymph nodes, 30, 30f
future directions of, 714–715 Italian Tamoxifen Anastrozole (ITA) trial, 740, 740f Lateral mammary branches, 28–29
randomized studies of, 713–714 Ixabepilone, for metastatic breast cancer, 888t, 890t, Lateral pectoral nerve, 27, 27f
Intraoperative ultrasound, for HUG, 469 894 anatomy of, surgical, 388, 389f
Intrapatient heterogeneity and clonal evolution, 322, toxicity profile of, 894 Lateral thoracic artery, 26
323f Latissimus dorsi musculocutaneous flap, 790–791,
Intrathecal chemotherapy (ITC), 956–957 J 790f
Invasion-metastasis cascade, 284 Jacobson, H.I., 907 Latissimus flap, surgical technique for, 481–482,
Invasive breast cancer Japan, trends in selection of mastectomy therapies, 483f–484f
breast conserving therapy for, 693–705 2000 to 2016, 433–434, 434f Lawson, W., 907
randomized trials in, 693–694, 694t Japan Clinical Oncology Group (JCOG), in LCIS. See Lobular carcinoma in situ.
chemoprevention of, 557–558 systemic therapy, 872 le Dran, Henri François, 5–6, 6f
HR-positive, 913–919 Japanese Breast Cancer Society (JBCS), 433–434 Leiomyoma, 162
lobular neoplasia and, risk factor for, 553–554 Jensen, E.V., 907 Leiomyosarcoma, 162
Invasive carcinoma(s) John Wayne Cancer Institute (JWCI), 604 Leonides, 2
with extensive intraductal component, 351, 352f Joint Center for Radiation Therapy, 467 Leptomeningeal metastatic disease (LMD), 942–943
lobular Joint pain chemotherapy for, 956–957
bilateral breast cancer and, 969–970 bone and, in adjuvant endocrine therapy, 750 intrathecal, 956–957
mammography of, 345 musculoskeletal complaints, 1017 systemic, 957
sentinel lymph node dissection for, 612 J-score, 199 corticosteroids for, 946–947
Invasive cribriform carcinoma, 149, 149f Juvenile fibroadenoma, 126 differential diagnosis of, 944–945
Invasive diagnostic procedures, 335–336 Juvenile hypertrophy, 47, 48f magnetic resonance imaging of, 945f
Invasive ductal carcinoma, of no special type. See No Juvenile papillomatosis, 91 medical management of, 956
special type (NST) carcinoma. pathophysiologic mechanisms of, 943
Invasive early-stage breast cancer, adjuvant endocrine K radiation for, 958
therapy for, 737–747 Karnofsky Performance Score (KPS), 946 radiologic evaluation of, 944–945
disease-free survival of, 745t Kaufman axillary treatment scale (KATS), 599 treatment of, 956–958
fertility considerations in premenopausal women Kennedy syndrome, gynecomastia and, 108–109 toxicity of, 958
with, 746–747 Keratinization, disorders of, 182–183 Lerner, L.J., 907
menopausal status as, 737 Keyhole approach, for skin-sparing mastectomy, 400 Leser-Trelat sign, 172
postmenopausal women in, 737–743 Keyhole limpet hemocyanin (KLH), 929 Lesions
premenopausal women in, 743–747 Keynes, Geoffrey, 14–15, 462 of breast
Invasive lobular breast cancer, 655 Ki67 (proliferation marker), 204–205, 205f benign, 116–129
Invasive lobular carcinoma (ILC), 147, 148f in endocrine therapy, 914 without cancer risk, 116–118
mammography of, 345 Klinefelter syndrome, 974 excised, 648, 648f
Invasive mammary carcinoma, 147, 148f gynecomastia and, 108 high-risk, 116–129
Invasive Paget disease, 171, 171f Kocher incision, 392f premalignant, 116–129
Iodine, for breast pain, 83 Kondoleon, Emmanuel, 527 in lateral aspect, 386
Ionizing radiation, breast cancer and, 217–218 Küster, Ernst, 8 Letrozole, effect of, 911
Ipilimumab, 329 Lett, Hugh, 15
Ipsilateral breast tumor recurrence (IBTR), 463, 648 L Level meta-analysis of margin width, 648
breast conserving surgery and radiation for, 694t LABC. See Locally advanced breast cancer. LHRH. See Luteinizing hormone releasing hormone.
characteristics and management of, 702–703, Lactating adenoma, 89–90, 126 Lichen planus-like keratosis, 183
703t Lactation Lichen sclerosis et atrophicus, 188
clinical factors of, 694–696 breast physiology in, 53–55 Lifestyle factors, and breast cancer
genetic factors in, 696 clinical correlates of, 55–56 epidemiologic evidence in, 1045–1046
gross multifocal/multicentric disease in, 696 delayed onset of lactation as, 55 mechanisms in, 1046–1047
margin status in, 697–698, 698t impact on breast cancer risk as, 56 Lifestyle Intervention Study in Adjuvant (LISA)
pathologic factors in, 696–699 lactational success as, 55–56 trial, 1047, 1048t
1098 Index

Lifestyle interventions, 1039–1048 Lobules, anatomy of, 21, 22f Locally advanced breast cancer (LABC) (Continued)
with disease end points, 1047 Lobuloalveolar growth, 45 prognostic factors for, 820
with quality of life (QOL) outcomes, 1046–1047 Local and distant disease-free survival rates, for radiation therapy for, 726–735
special consideration in, 1043–1044 modified radical mastectomy, 447t for inoperable LABC, 730
Li-Fraumeni syndrome, 239, 247, 299 Local recurrence neoadjuvant chemotherapy followed, 729
Ligand-binding domain (LBD), 274–275, 291 after breast conserving therapy, 987, 987f neoadjuvant systemic therapy and, 729–730
Linear accelerators (LINACS), 663 axilla, management of, 988 rationale for use of systemic therapy for,
Lipid profile, tamoxifen and, 908 salvage mastectomy for, 988 727–728
Lipoma(s), 161 after mastectomy or breast-conserving therapy, reconstructive techniques for, 788–789
mammography of, 344 426f rectus abdominis transposition and free flaps for,
Lipomastia, 104 cumulative incidence, after, 465f–466f 791, 791f
Lipomatous neoplasms, 161 of ductal carcinoma in situ, 673–674 role of sentinel lymph node biopsy for, 782t,
Liposarcoma, 161, 161f biological markers and, 674 785–786
Liposomal doxorubicin, for metastatic breast cancer, clinical factors in, 673–674 RT alone for operable, 729
888t histologic subtype and, 674 staging of, 820
Liposuction, for lymphedema, 528 imaging factors in, 674 staging system revisions and implications of, 778,
“Liquid biopsy,” 865–866 margin status and, 674 779f
Lister, Joseph, 7–8 pathologic factors in, 674 studies for, 729
Litigation gap, in delayed diagnosis, 1065–1066 patient factors in, 673–674 surgical procedures for, 778–801
Liver, metastases of, 802–803 tumor size in, 674 survival with, 819–820
Liver cirrhosis, gynecomastia and, 108 extensive intraductal component and, 466 timing of therapies for, 786–787, 787b, 787f
LN. See Lobular neoplasia. radical mastectomy and recurrence after breast unimodal treatment approaches for, 779–780
Lobes, anatomy of, 21 conservation therapy in, 424–425, 427f radiotherapy as, 780
Lobular carcinoma, invasive risk factors for, 466 surgery as, 779–780
bilateral breast cancer and, 969–970 tumor volume and, 397 vertical rectus abdominis myocutaneous flap for,
mammography of, 345 Local relapse, after mastectomy, 984–985, 985f 791
Lobular carcinoma in situ (LCIS), 121, 130–144, Localized sclerosing lesions, 121–124 Locally advanced disease, male breast cancer,
655, 992 Locally advanced breast cancer (LABC), 727f, 978
bilateral breast cancer and, 970 819–831, 840 treatment of, 977–979
of breast, 553–561 axillary lymph node dissection in, 784 Locoregional postmastectomy recurrences, 981
aromatase inhibitors for chemoprevention, 558 technique of, 785, 785f Locoregional recurrence (LRR)
breast conservation in patients with, coincident breast conserving surgery for, 784, 784b, after mastectomy, 808–813, 981–985, 982f
with invasive cancer, 559–560 827–828 definitions of, 808, 809f
changing incidence of, and influence/exogenous chest wall closure for, 789–798 detection and diagnosis of, 809f, 811–812
hormones on lobular carcinogenesis, 557 combined modality treatment for, 821–822 incidence of, 808–811
clinical features of, 556 radiotherapy as, 821 local treatment, 812
clinical presentation, natural history, and surgery as, 821 radiation therapy, 812–813
biologic significance of, 556–557 core needle biopsy for, 779f survival after, 812
core needle samples showing, 558–559 delayed reconstruction for, 788–789, 789f systemic therapy, 813
definition of, as unique stage 0 preinvasive diagnosis of, 820 for histologic examination at mastectomy, 451t,
“cancer,” 554 epidemiology of, 819 453f
diagnosis, subsequent invasive carcinoma after, evolution of local therapy for, 820–821 incidence of, 982, 982f
risk of, 556–557, 556t full-thickness chest wall resection of, 787–788 risk factors for, 1011
endocrine chemoprevention for, 557–558 general treatment paradigms of, 727 surveillance for, 1011–1014
female steroid hormones and, 557 guideline statements for, 728–729 Locoregional therapy, 874–875
histopathology of, 554–556 immediate reconstruction for, 788 Logistical hurdles, in the detection of axillary lymph
immunohistologic features and molecular incidence of, 726–727 node micrometastases, 633
genetics of, 556 inoperable, 730 Long thoracic nerve (respiratory nerve of Bell), 27
morphologic features of, 554–555, 554f–555f locoregional radiation targets and techniques for, anatomy of, 389f
pleomorphic, 554f–555f, 555 732–734 identification of, 440–441
as premalignant lesion, 553, 554t management for, pretreatment evaluation, preservation of, 391–392
as risk factor for invasive breast cancer and diagnosis and, 778–779 Low dietary fat, for breast pain, 83
lobular neoplasia, 553–554 multidisciplinary approach for, 799 Lower inner quadrants, incision for, 396
surgical excisional biopsy showing, 558 multimodal approaches for, 780–784 Lower outer quadrants, incision for, 396, 406f
surgical intervention for, 558–561 adjuvant therapy as, 783–784 Low-pressure tamponade, 961
surgical prophylaxis with, defined role for, chemotherapy as, 781–782 LRR. See Locoregional recurrence.
560–561 early trials of, 780–781 Ludwig studies, of axillary lymph node
breast cancer risk and, 209 endocrine therapy as, 783 micrometastases, 632–633
classic type of, 132, 132f targeted therapy as, 783 Luini’s technique, 384
pagetoid spread of, 132, 133f multimodality approach for, 820 Lumpectomy, 323, 469. See also Breast conservation
pathology of, 143–144, 143f myocutaneous flap for, 790–791 therapy.
pleomorphic type of, 132, 132f neoadjuvant antiestrogen therapy for, 824–827 Lumpectomy cavity shave margin, 639t–640t
unique biology of, 130–133 neoadjuvant anti-HER2-based therapy for, Lung cancer, metastatic to breast, 347f
Lobular hyperplasia, atypical, 91. See also Atypical 823–824 Lung carcinoma of, gynecomastia due to, 107
lobular hyperplasia. neoadjuvant chemotherapy for, 781, 822–823 Lung metastases, 803–804. See also Pleural
Lobular neoplasia (LN), 143, 553 neoadjuvant systemic therapy and radiation for, metastasis(es).
breast magnetic resonance imaging for, use of, 729–730 Lupus mastitis, 190
559 outcomes of, 727 Lupus panniculitis, 190
 Index 1099

Luteal phase, 57 Lymphedema, 492–493 Magnetic resonance imaging (MRI), 334, 337,
in menstrual cycle, 45, 47f management of, 1015–1016 355–357, 356f
Luteinizing hormone releasing hormone (LHRH), in in postmastectomy patient, 514–530 for axillary metastasis of unknown primary,
endocrine therapy, 737 acute, 522 1000
Luteinizing hormone-releasing hormone (LHRH) after sentinel lymph node mapping, 521 of the breast, 68
agonists, 915 anatomy for, 515–518 for breast imaging, 468–469
for breast pain, 84 breast drainage in, 515, 515f for early breast cancer, 644
Lymph capillaries, 515–516, 517f, 519 internal mammary lymphatics in, 516 in follow-up care, 1013–1014, 1014t
Lymph collecting vessels, 517f lymph nodes of upper extremity in, standardized terminology for reports on, 356
Lymph flow, 30f–31f, 32–34 516–518, 518f typically malignant findings on, 356–357, 357f
Lymph node(s), 784 lymphatics of upper extremity in, 516–518, Magnetic resonance imaging-guided biopsy, 380t,
axillary 518f 382
abnormal, mammography of, 353, 354f superficial lymphatics in, 515–516, 517f MagSweeper (Illumina), for CTC enrichment,
anatomy of, 30–31 axillary lymph node dissection and, 515t, 521 861–862
clinical staging of, 251 chronic, 522 Maimonides, Moses, 4
dissection of, 460–461 classification of, 522 Major histocompatibility complex (MHC) class I
grouping of, 516–517, 518f etiologic risk factors of, 521 expression, 924
micrometastases to, 254 history of, 514 Male breast cancer (MBC), 974–980, 1043–1044
hottest, 624 incidence of, 514, 515t, 521 adjuvant radiation therapy for, 978
internal mammary, radiotherapy for, 677 lymphangiosarcoma and, 514, 529–530, 530f adjuvant systemic therapy for, 978
supraclavicular management of clinical features of, 976
radiotherapy for, 677–678 nonoperative, 524–526 delayed diagnosis of, 1070
recurrence in, after mastectomy, 983 operative, 527–529 diagnosis of, 976–977
targeted dissection of, 786 measurement of, 522–524 ductal carcinoma in situ in, 977
of thoracic cavity, 35–36 circumferential, 523 epidemiology of, 974, 975f
of thoracic wall, 33f, 34–35 multiple frequency bioimpedance analysis in, immunohistochemical and molecular
Lymph node biopsy, sentinel, 31–32, 785–786 523–524 characteristics of, 977
history of, 14 rating scales in, 523 localized and locally advanced disease, treatment
lymphedema and, 515t, 521 tonometry in, 523 of, 977–979
during pregnancy, 995 water displacement in, 523 management of, 980
Lymph node metastasis, percentage of, 613t pathophysiology of, 519–521 pathology of, 977
Lymph node status, 539–542 patient history of, 522–524 prognosis of, 979–980
axillary, 251, 540–541 prevention of, 526 regional nodes, management of, 977–978
internal mammary, 541–542, 541f axillary reverse mapping for, 517, 519f, risk factors for, 974–976, 975b, 976f
intramammary, 542 527 surgical management of, 977
pathologic assessment of, 542 sentinel lymph node, 526 survivorship issues and surveillance, 980
sentinel lymph node mapping for, 541, 541f primary, 522 tamoxifen for, 978
supraclavicular, 542 from radiation treatment, 522 treatment of, 979
Lymphadenectomy, sentinel. See Sentinel risk factors for, 514 Malignancy, second, 724
lymphadenectomy. secondary, 522 Malignant fibrous histiocytoma (MFH), 159–160
Lymphangiosarcoma, 514, 529–530, 530f sentinel lymph node biopsy and, 515t, 521 Malignant masses, mammography of, 345–351
Lymphatic drainage, 30–36, 31f stages of, 522 breast metastases from extramammary
lymph flow in, 30f–31f, 32–34 risk factors for, 493 malignancies as, 347, 347f
lymph nodes “Lymphocyte predominant,” definition of, 927 with calcifications, 349–350, 351f
axillary, 30–31, 30f Lymphocyte-predominant breast cancer (LPBC), colloid carcinoma as, 346, 346f
of thoracic cavity, 35–36 927 intracystic papillary carcinoma as, 346–347, 347f
of thoracic wall, 34–35 Lymphocytes invasive ductal carcinoma of no special type, 345
routes for metastases and, 390–391 in immunity, 924 invasive papillary carcinoma as, 346–347, 347f
sentinel lymph node biopsy and, 31–32 prognostic role of tumor-infiltrating, 927–928 medullary carcinomas as, 345–346, 346f
Lymphatic fluid contents, 590 Lymphocytic mastitis, 182 tubular carcinomas as, 345, 345f
Lymphatic function and nodal metastases, Lymphoma(s), 194–195, 195f Malignant melanoma, 193–194, 194f
590–591 primary, of breast, 163–168, 164f Malignant pericardial effusion (MPCE), 934
Lymphatic mapping. See also Sentinel lymph node Lymphoscintigraphy Malignant pleural effusion (MPE)
(SLN) mapping. intraoperative gamma-probe detection, 623 causes of, 935t
for breast cancer, 604–630 preoperative, 623f diagnosis and management of, 934–941, 938b
combined technique for, 624, 624f for sentinel node, identification, 607 imaging of, 935–936
injection technique for, 621f Lymphovascular invasion (LVI), 534–535, immunohistochemistry for, 937
intraoperative, selection of optimal dye for, 633–634 prognosis of, 941
618–622 Lymphovenous shunts, for lymphedema, 528–529, thoracentesis of, 936–937, 937f
radiolocalization and, 622–624 528f–529f treatment of, 937–941
with vital dye, 618–622 pleural decortication in, 940
“Lymphatic permeation,” 392 M pleural space drainage in, 938–940
Lymphatics M stage, in TNM system, 548, 548t sclerosing agents in, 940–941
normal function of, 520 Macromastia, 486–487 surgical pleurectomy in, 940
of upper extremity, 516–518, 518f Madden, retrospective trial, results of, 445t thoracoscopic surgery in, 940
of upper torso, 516f–517f Madden techniques, 392–393 Mammaplasty
Lymphatic-venous-lymphatic anastomoses, for Magnetic resonance guided focused ultrasound augmentation, 489–490
lymphedema, 528–529 (MRgFUS), 660–661, 661f reduction, 486–489
1100 Index

MammaPrint (70-gene assay), 539, 781–782 Mammography (Continued) Mass(es) (Continued)

of endocrine therapy, 914 postsurgical scars as, 352 calcifications in, 347–350, 348f
prognostic and predictive value of, 261 radial scars as, 352 density of, 341, 343f
Mammary adenocarcinoma, 386 malignant, 345–351 fibroadenomas as, 344, 344f
Mammary branches, 28 breast metastases from extramammary malignant, 345–351
Mammary bud, 38f malignancies as, 347, 347f breast metastases from extramammary
Mammary duct ectasia, 180 colloid carcinoma as, 346, 346f malignancies as, 347, 347f
Mammary duct-associated inflammatory disease intracystic papillary carcinoma as, 346–347, colloid carcinoma as, 346, 346f
sequence (MDAIDS), 97 347f intracystic papillary carcinoma as, 346–347,
Mammary ductoscopy, 69 invasive ductal carcinoma of no special type, 347f
Mammary gland(s), 37. See also Breast(s). 345 invasive, with extensive intraductal
active, in pregnancy and lactation, 22–23, 23f invasive papillary carcinoma as, 346–347, component, 351, 352f
hormonal regulation of, 23–24 347f invasive ductal carcinoma of no special type,
inactive, 21–22, 23f medullary carcinomas as, 345–346, 346f 345
postmenopausal involution of, 288 tubular carcinomas as, 345, 345f invasive papillary carcinoma as, 346–347,
postnatal, 287 normal findings on, 339–340, 342f 347f
pregnancy and lactation, 288 screening, 334, 337 medullary carcinomas as, 345–346, 346f
prenatal or fetal, 286–287, 287f craniocaudal view of, 337, 338f–339f tubular carcinomas as, 345, 345f
puberty, 287–288 in follow-up care, 1013 margins of, 341
stages of, development, 286, 287f importance of compression in, 337 self-discovered, delayed diagnosis of, 1066–1067
stem cells of, 288 mediolateral oblique view of, 337, 338f shape of, 340–341, 342f
stemness and clonal evolution, 288, 289f shape of, 340–341 ultrasound of
venous drainage of, 36 standardized terminology for reports on, 339 benign, 341–344, 344f
Mammary hamartoma, 158 Mammography Quality Standards Act, 339 malignant, 354, 355f–356f
Mammary milk line, 21f, 38f Mammography reports, standardized terminology Massage therapy, for lymphedema, 525
Mammary ridges, 38f for, 339 Mastalgia, 79
Mammary stem cell regulatory pathways, 309 Mammostrat, 261, 781–782 Mastectomy, 478, 478f
Mammary tissue, consists of, 308–309 Manchester Regional Breast Study, 450–451, breast conserving surgery and, 727
MammaTyper, 262 451t chronology of, 423t
Mammogram Manchester system, for staging, 543, 543t complications of, 492–498
false-negative, 1067–1069 Manchester trial results, 447t deep venous thrombosis, 497–498
during pregnancy, 994 Mannan-MUC1 vaccine, pilot phase III study of, hemorrhage, 496–497
screening for breast cancer with, 643, 646f 929 injury to neurovascular structures, 497
Mammographic breast density Margin(s) lymphedema as (See Lymphedema)
in breast cancer, 216, 220 cavity shave margin technique for, 639 pneumothorax, 496
dietary fat and, 216 emerging technology for, 641–642 postmastectomy pain syndrome, 498
exogenous hormones and, 216 frozen section analysis of, 640 seroma, 493–496, 495f, 495t–496t
Mammography, 67–68, 337–353 gross intraoperative inspection of tumor, 639 tissue necrosis, 496
abnormal finding on, 340–353 of Halsted radical mastectomy, 441f wound infection, 493, 494f
of axillary lymph nodes, 353, 354f intraoperative cytologic evaluation by touch for DCIS, 566
for breast cancer screening, 643 preparation for, 640, 641t design of incisions for, 394–396
of calcifications, 347–350, 348f intraoperative specimen radiography for, 641 central and subareolar primary lesions,
benign, 348–349, 348f–349f intraoperative ultrasound of, 640–641, 641t 394–396
fibroadenomas, 344f of mass, 341, 343f for lower inner quadrants, 396
secretory, 348–349 pathologic assessment of, and specimen handling, for lower outer quadrants, 396
vascular, 348, 349f 639–642 for upper inner quadrants, 396
linear, 347–348, 348f surgical, in breast conserving therapy, for upper outer quadrants, 396
malignant, 349–350, 351f 637–642 for early breast cancer, 649, 651f
milk of calcium as, 349, 350f of tumor, 386–387 evolution of surgical techniques for, 391–394
regional, 347–348 Margin status followed by adjuvant chemotherapy, 729
segmental, 347–348, 349f in breast conserving surgery and radiation, general principles of, 386–421, 420t
diagnostic, 337–339, 341f 697–698, 698t Halsted, 422–442 (See also Radical
spot compression views in, 337–339 for DCIS, 139–140 mastectomy)
for women 30 years of age, 339 Margin-positive partial mastectomy, frequency of, history of
digital, 337 639 in eighteenth century, 6
history of, 17 Mascagni, Paolo, 5 in nineteenth century
indirect signs of breast cancer on, 352–353 Mass(es) American surgery, 8–9, 9f–10f
architectural distortion as, 352, 353f in clinical breast examination, 332–333 European surgery, 8
asymmetry as, 352, 353f mammography of, 340–351 in Renaissance, 4, 5f
margins of, 341, 343f benign, 341–344, 344f in twentieth century, 12
of masses, 340–351 fibroadenomas as, 344, 344f local recurrence, factors affecting, 396–397
benign, 341–344, 344f galactoceles as, 344 local relapse after, 984–985, 985f
fibroadenomas as, 344, 344f hamartomas as, 344, 344f locoregional recurrence after, 808–813, 981–985
galactoceles as, 344 intramammary lymph nodes as, 344, 345f mammographic follow-up after, 361, 361f
hamartomas as, 344, 344f lipomas as, 344 margin-positive partial, frequency of, 639
intramammary lymph nodes as, 344, 345f oil cysts as, 344, 345f modified radical (See Modified radical
lipomas as, 344 postsurgical scars as, 352 mastectomy)
oil cysts as, 344, 345f radial scars as, 352 nipple-sparing, 414, 415f, 418f–419f
 Index 1101

Mastectomy (Continued) Memory and Attention Adaptation Training Mesenchymal-epithelial transition (MET),
with or without immediate breast reconstruction, (MAAT), 1019, 1045 311–312
420t Menopausal symptoms Metachronous contralateral breast cancer, 970t
for Paget disease, 174 adjuvant endocrine therapy and, 749 risk of, 991
during pregnancy, 995 in breast cancer survivors, 1018 Metaplastic carcinoma, 151, 152f
psychologic distress due to, 1043 Menopause Metastasis(es)
radiation therapy after, 676 in breast cancer patient, 1024–1030, 1025t axillary (See Axillary metastasis)
radical (See Radical mastectomy) antidepressants for, 1025–1026, 1026t bone (See Bone metastasis(es))
reconstruction after (See Reconstruction) cardiovascular disease in, 1028–1029, 1030b brain (See Brain metastasis(es))
salvage, 437 clonidine for, 1026 CNS (See Central nervous system (CNS)
treatment for local recurrence after breast complementary and alternative methods for, metastasis(es))
conserving therapy, 988 1026–1027 distant, in staging, 548
simple (See Total mastectomy) depression in, 1027–1028, 1027b from extramammary malignancies, 347, 347f
skin-sparing (See Skin-sparing mastectomy) estrogen-based therapy, alternatives to, for history of term, 8
subcutaneous, 990–991 management of vasomotor symptoms, lymphatic drainage and routes for, 390–391
topographic surgical anatomy for, 388–391 1025–1027 micro (See Micrometastasis(es))
lymphatic drainage and routes for metastases experience of, 1024 pericardial, 961–966
in, 390–391 gabapentinoids for, 1026 pleural (See Pleural metastasis(es))
neurologic innervation of pectoral muscles in, hormone therapy for, 1024–1025 sentinel node, predictors of, 615–618
388–390, 389f osteoporosis in, 1028, 1028b, 1029t solitary, 802–807
vascular distribution in, 390 progesterone analogs, 1026 tumor size and, 532–533, 533t
total (See Total mastectomy) topical estrogens option for, 1027 Metastatic bone disease, 901–902
wound care and, 492–498 alternatives to, 1027 Metastatic breast cancer (MBC), 862–863, 942
Mastectomy deformity, definition of, 478 in breast cancer survivors, 1053–1054 antiangiogenic therapy for, 899–901, 900t
Mastitis, 93–95, 181–182, 181f breast physiology in, 56 chemotherapy for, 885–906, 903t
evaluation of, 93, 94f clinical correlates of, 56 alkylating agents in, 893
idiopathic granulomatous, 98–103, 101f hormones in, 56 anthracyclines in, 890–891
diagnosis of, 99–100, 100b, 102f morphology of, 56 antimetabolites in, 893–894
etiology of, 100 breast regression after, 23–24 fluoropyrimidines as, 893–894, 894f
imaging of, 99, 101f–102f chemotherapy-induced, 1052 gemcitabine as, 894
treatment of, 100–103 Menstrual cycle, 45–46, 47f combination, 888–889, 889t–890t
lactational, 95–96 breast pain and, 79 epothilones as, 894
management of, 94–95, 95f Menstrual phase, in menstrual cycle, 45, 47f first-line regimen of, 888
microbiology of, 93–94 MER-25, 907 single-agent, 888–889, 889t–890t
periductal, 88 (See also Subareolar abscess) Merit-Based Incentive Payment System (MIPS), taxanes in, 891–893
plasma cell, 182 (See also Subareolar abscess) 506–507 vinca alkaloids as, 895
presentation of, 93 Merocrine secretion, 22–23 circulating tumor cells in (See Circulating tumor
Mastopexy, 489 Mesenchymal neoplasms, of breast, 156–163 cells (CTCs))
Mathematical scoring system, 595 breast sarcoma, 156 in elderly, 902–903
Maximum tolerated dose (MTD), 366–367, 367f fibroblastic and myofibroblastic, 158–160 endocrine-sensitive, 888f
Mayo Clinic studies, 265, 265f fibromatosis, 158, 158f epidemiology of, 885
MBC. See Metastatic breast cancer. hemangiopericytoma, 159 future of systemic therapy for, 906
McGuire, W., 15–16 inflammatory myofibroblastic tumor, 159 HER2-positive, 895–899
McWhirter, Robert, 14–15 malignant fibrous histiocytoma, 159–160 investigational agents in, 900t
MD Anderson Neoadjuvant and Adjuvant myofibroblastoma, 158, 159f lapatinib for, 898
Chemotherapy Protocols, 781b pseudoangiomatous stromal hyperplasia, 159, T-DM1 for, 898
MDAIDS. See Mammary duct-associated 159f trastuzumab for, 895
inflammatory disease sequence. fibroepithelial, 156–158 investigational agents in, 900t
Medial mammary arteries, 28 fibroadenoma, 156 local therapy for, 886–887
Medial mammary nerves, 29 mammary hamartoma, 158 medical evaluation in, 886
Medial pectoral nerve, 27f, 28 phyllodes tumor, 156–158, 157f–158f monitoring response to therapy in, 905–906
anatomy of, surgical, 388–390, 389f lipomatous, 161 with nonsteroidal AIs, 920t
Medially located neoplasms, 386 lipoma, 161 novel agents in, 899
Median nerve, lateral root of, 27, 27f liposarcoma, 161, 161f prognostication of, 885–886
Medical malpractice, 1058b, 1059, 1059t myogenic, 162–163 selecting therapy for, 887–889, 888f
Medications, abstention from, in breast pain, 85 leiomyoma, 162 special considerations of, 902–905
Mediolateral oblique (MLO) view, of screening leiomyosarcoma, 162 surgery in, 887
mammography, 337, 338f rhabdomyosarcoma, 162–163 tamoxifen for, 908
Medroxyprogesterone acetate, for mastalgia, 86 neural, 162 therapeutic goals for, 885
Medullary carcinoma, 150, 150f benign peripheral nerve sheath tumors, 162 triple-negative, 903–905, 904f
mammography of, 345–346, 346f granular cell tumor, 162 Metastatic disease, 838
prognosis for, 255 osseous, 163 management of intact breast primary in setting of,
Megestrol acetate, 911 vascular, 160–161 867–875
Melanoma, versus Paget disease, angiomatosis, 160 American Society of Clinical Oncology
Melanoma-specific T cells, 930–931 angiosarcoma and related syndromes, 160–161, (ASCO) in, 872–873
Memorial Sloan Kettering Cancer Center 160f asymptomatic primary tumors in, 874–875
(MSKCC), 594–595 hemangioendothelioma, 160 locoregional therapy in, 874–875
in locoregional recurrence, 679 hemangioma, 160 nonsurgical group in, 872, 873f–874f
1102 Index

Metastatic disease (Continued) Mini-Mental State Examination (MMSE), 948 Mucinous (colloid) carcinoma, multicentricity in,
radiotherapy as, 869t Misdiagnosis. See Delayed diagnosis. 550.e1f
randomized prospective trials for, 871–874, Mitogen-activated protein kinase (MAPK), Mucoepidermoid carcinoma, 151
871t 283 Multicenter lymphatic mapping trials, for sentinel
de novo stage IV breast cancer patients in, Mitotic activity index (MAI), 535–536, 536f lymph node, 609–610
873–874 MLO (mediolateral oblique) view, of screening Multicentricity, 549–550
induction systemic therapy in, 871–872, mammography, 337, 338f anatomy of the breast and, 549, 550.e2f
873f–874f Modified Halsted incision, 392f biological studies of, 550
locoregional therapy before systemic therapy Modified radical mastectomy (MRM), 443–448, case studies on, 550.e1–550.e2
in, 872–873 729–730, 837, 977 clinical follow-up studies on, 550–551, 551f
retrospective analyses of, 868–871 anesthesia and positioning for, 457 clinical implications of, 551–552
in de novo stage IV breast cancer, 869t, 870 closure of, 461 of DCIS, 550, 550.e2f
locoregional control in, 870 evolution of technique for, 392 high-grade comedo, 550.e2f
radiotherapy for, 870 historical evolution of the surgical technique for, invasive carcinoma with, 549–550,
selection biases in, 870–871 443, 444t 550.e1f–550.e2f
surgical resection of primary tumor and limits of, 458f definition of, 552
survival in, 868–870, 869f, 869t for Paget disease, 174 distance of, 549
surgery as position of patient for, 457f of extensive intraductal carcinoma, 549f, 551
axillary, 868 postoperative care for, 461 independently originating breast carcinomas and,
overall survival of, 872–873 prospective trials for, 445–448, 446t 549
timing of, 870–871 on local recurrence rates of, 445 mammogram on, 550.e1, 550.e2f
repeat immunohistochemical studies on, Manchester trial results for, 447t molecular biology of, 550
200–201 on overall survival, 445–448 natural history of, 549
Methotrexate, 324 University of Alabama, 447t prevalence of, 549
Methylation, DNA, 304 reconstruction with, 410f primary or dominant lesion in, 550.e1
Methylation-specific polymerase chain reaction removal of breast for, 458, 459f–460f quadrant of, 549
(MSP), ductal lavage and, 63 retrospective studies of, 443–445 radial distribution of, 549–550
Methylxanthines, breast pain and, 82–83 recurrence rate of, 443–444 secondary lesions in, 550.e1
Meticulous hemostasis, 648 results of, 445t three-dimensional imaging of, 549
Meyer, Willie, 12, 12f, 422 survival rates for, 443, 446t Multifield IMRT, 681, 682f–686f
Meyer technique, for radical mastectomy, 391 with sentinel lymph node biopsy, for index tumor, Multifocal or multicentric disease, 613
Microarray in Node-Negative Disease May Avoid 386 Multifocality, 549
Chemotherapy (MINDACT), 257 skin excision with, 398 Multiple frequency bioimpedance analysis, for
Microinvasion, 564 skin incision and skin flap development for, lymphedema, 523–524
ductal carcinoma in situ with, 612–613, 613t 457–458 Muscle atrophy, 1031
Microlobulated margins, 341, 343f skin-sparing, 412f Musculoskeletal complaints, after treatment, 1017
Micrometastasis(es), 594, 595t sterile skin preparation for, 457 Musculoskeletal system, in rehabilitation, 1031
axillary lymph node, 254 technique of, 457–461 Mutator phenotype, 285
classification of, 631–632 Molecular breast imaging (MBI), 335 Mutual exclusivity, 304
detection and significance of, 631–636 Molecular Grade Index, 261–262 Myelodysplasia, in breast cancer survivors, 1021
frequency and prognostic significance of, Molecular markers, ductal lavage and, 63–64 Myelography, 945
632t Molecular profiling, 539 Myeloid-derived suppressor cell (MDSC), 924
Micropapillary carcinoma, 150, 150f Molecular staging, 542 Myelosuppression, 716
Micropapillary ductal carcinoma in situ, 136f Molecular subtype, 538, 538f Myofibroblastic neoplasms, 158–160
MicroRNAs, 304–305 of breast cancer and response, to neoadjuvant Myofibroblastoma, 158, 159f
Microvascular composite tissue transplantation, chemotherapy, 839–840 Myogenic neoplasms, 162–163
794 Mondor disease, 189–190
Microwave ablation, 656, 659–661, 660f Monoclonal antibodies, 329 N
Middle ages, history of breast cancer therapy in, commonly used, 201, 201t N stage, in TNM system, 546–548, 546t–547t
2–4 Mononeuropathies, 1034–1035 NAF. See Nipple aspiration fluid.
Arabic, 4 Mood disturbances, adjuvant endocrine therapy and, Nashville Breast cohort studies, 264–265
Christian, 2–3, 3f 750 Nathanson, I., 15–16
Jewish, 3–4 Moore, Charles Hewitt, 7, 8f National Accreditation Program for Breast Centers
Mifepristone, 280 Morton, Donald, 14, 14f (NAPBC), 500
Milan II trial, 469 Motexafin gadolinium, 955 National Accreditation Program for Breast Centers
Milan trial, 626–627 Moynihan, Berkeley, 514 Standards Manual, 649, 650b
of elderly patients, 652 MPCE. See Malignant pericardial effusion. National Cancer Database (NCDB) study, 449
Mild ductal epithelial hyperplasia, 88 MPE. See Malignant pleural effusion. on breast conservation therapy, 462
Milk MRI. See Magnetic resonance imaging. in metastatic disease, with intact breast primary,
of calcium, 349, 350f MRL-41, 907 868
component of, 22–23 MSKCC nomogram, 594–595 National Cancer Institute and National Coalition
secretion of, 22–23 drawback of, 595–596 for Cancer Survivorship, 1031
witch’s, 43 MTD (maximum tolerated dose), 366–367, 367f National Cancer Institute of Canada (NCIC)
Milk fistula, 96 MUC-1 gene, in metastatic breast cancer, MA.17 study, 742, 742f
Milk let-down, 55 905–906 MA.27 trial, 739, 739f
Milk pore, 59f Mucin 1 (MUC-1), 328 National Cancer Institute of Canada Clinical Trials
Milk stasis, 55 Mucinous carcinoma, 149, 149f Group (NCIC CTG), 880
MINDACT, 261 mammography of, 346, 346f MA20 trial, in radiotherapy, 677
 Index 1103

National Cancer Institute’s Common Neoadjuvant chemotherapy (Continued) Nipple(s)

Terminology Criteria for Adverse Events for locally advanced breast cancer, 821–823 anatomy of, 21, 59f
(CTCAE), 717 anti-HER2-based therapy, 823–824 dermatoses of, 179–180
National Comprehensive Cancer Network (NCCN), assessment of response to, 827 erosive adenomatosis of, 184–185, 184f
239, 503, 821–822 predictors of response to, 827 Paget disease of (See Paget disease)
recommendations of, 234–236 randomized clinical trials of, 821t, 825t supernumerary (accessory) (See Polythelia)
aromatase inhibitor recommendation, 236 tamoxifen, 826t Nipple adenoma, 128
raloxifene recommendation, 235–236 locoregional recurrence risk on NSABP trials of, versus Paget disease, 171–172
tamoxifen recommendation, 234 731, 732t, 733f–735f Nipple aspiration fluid (NAF)
for risk-based screening, 1009 mastectomy and, 730 biochemical composition of, 60–61
St. Gallen and, 752 molecular subtypes of breast cancer and response breast cancer risk and, 60
National Comprehensive Cancer Network (NCCN) to, 839–840 breast cancer with, 60f
Distress Management guidelines, for distress, neoadjuvant setting, for research and drug characterization and significance of, 57–61
1039–1040 development, 856 cytology and corresponding histology of, 60f
National Health Care Policy Stakeholder Quality radiation therapy and, 839–857 histologic classification to define cytologic changes
Improvement Objectives, 501t rationale for use of, 727 in, 58
National Institutes of Health Consensus response assessment after, 852, 853t Nipple discharges, 77, 91–92
Development Conference, 462 surgical management after, 852–854 bloody, 66
National Society of Genetic Counselors, 239 targeted therapy, 848–851 in clinical breast examination, 333
National Surgical Adjuvant Breast and Bowel Project Neoadjuvant endocrine therapy, meta-analysis of, clinical evaluation and management of, 64–72
(NSABP), 323, 451–453, 611, 781 826 algorithm for, 76f–77f
B-04 trial, 598, 603t NeOAdjuvant Herceptin (NOAH) trial, 824 examination in, 67
B-06 protocol, 568 Neoadjuvant hormonal therapy, history of, 17 history in, 66
B-14 trial, 918 Neoadjuvant radiation therapy imaging in, 67–71
B-17 Trial, 568 for breast cancer, 851–852, 851b cytologic evaluation of, 66f, 71–72
B-24 trial, 748f eligibility for, 840, 840t results of, 72t
B-32 trial, 627–628, 628f, 635 evaluation of candidates for, 841–846, 841b, diagnosis and surgical intervention for, 72–77
B-33 trial, 742, 742f 841f–846f minimally invasive techniques for biopsy of
B-35 trial Neoadjuvant systemic therapy intraductal lesions in, 75–76
IBIS-II DCIS trials and, 748–749, 748f for early-stage breast cancer, 752–762 outcomes of, 76–77
on tamoxifen, 912–913 radiation therapy after, 855–856 ductography-galactography for, 68–69
on breast conservation therapy, 462 Neoadjuvant therapy, 759–762 ductoscopy for, 69–71
B-06 trial, 463 advantages of, 760 etiology of, 64–66, 65t
P-1 chemoprevention trial, 908 breast and axillary assessments, 760–761 duct ectasia as, 65–66
National Surgical Quality Improvement Program limitations in, 760 intraductal papilloma as, 65, 65f
(NSQIP), 500, 640 outcomes and end points of, 846–847 lactational, 66
Natural killer T cells (NK T cells), 924 pathologic complete response, 761–762 nonbreast etiology, 66
NCCN. See National Comprehensive Cancer Neoadjuvant trastuzumab, potential benefit of, imaging in, 334–335
Network. 569–570 mammography for, 67–68, 75f
NCIC-CTG MA 20, in breast-conservation surgery, NeoALTTO trial, 848–850 minimally invasive techniques for determining
679 Neonatal gynecomastia, 104 risk of breast cancer with, 61–64
N-desmethyl tamoxifen, 230 NeoSphere trial, 850–851 ductal lavage as, 61–64, 61f
NDL. See Nipple duct lavage. Neratinib, 768 limitations of, 62–63
Necrosis, of nipple, 489 Neu oncogene, 302 mammary ductoscopy as, 69
Needle biopsy Neural neoplasms, 162 procedure for, 61–62
of axillary node, with unknown primary, Neurofibroma, 162 random periareolar fine-needle aspiration as, 64
1000 Neuropathy, after treatment, 1017, 1034–1036 sample collection for, 71
of early breast cancer, 644 brachial plexopathy, 1035 sample preparation for, 71
fine-needle aspiration, false-negative, chemotherapy-induced, 1035–1036 technical modifications for duct excision in,
1070–1071 diagnosis of, 1036 73–75
imaging-guided core, 357–358, 358f mononeuropathies, 1034–1035 trigger point for, 67
pleural, 937 radiculopathy, 1035 types of, 67
Nei Jing, 1 treatment of, 1036, 1036t ultrasound for, 67–68
Neoadjuvant antiestrogen therapy, 824–827 Neurovascular injury, after mastectomy, 497 Nipple duct lavage (NDL), 62–63, 62f–63f
Neoadjuvant chemotherapy, 781, 786t, 840t NeuVax, 930 diagnostic categories in, 61–62
antiangiogenic therapy, 851 New primary disease, surveillance for, of intraductal papilloma, 63f, 65
anti-HER2 therapy, 848–851, 849t–850t 1011–1014 limitations of, 62–63
by breast cancer subtypes, 847–848, 848t Newborn nipple discharge, 43 molecular markers and, 63–64
Cancer and Leukemia Group B (CALGB) on, NexCourse IHC4 assay, 262 Nipple inversion, 92
729 Next-generation sequencing (NGS), 282, Nipple reconstruction, 490
chemotherapy after surgery, 855 827 Nipple secretion, 57
conclusion and future directions, 856–857 on breast cancer genetics, 241, 241f Nipple-areola, preservation of, 398, 400f, 402f, 413f
eligibility for neoadjuvant radiation therapy, 840, Night sweats, in breast cancer survivors, Nipple-areolar complex (NAC), 456
840t 1018 dysfunction of, 489
evaluation of candidates for, 841–846, 841b, Night-shift work, breast cancer and, 217 Nipple-coring, 399
841f–846f Nimesulide, for breast pain, 85 Nipple-sparing mastectomy, 414, 415f, 418f–419f,
followed by resection or radiation, 729 Nineteenth century, history of breast cancer therapy 456
history of, 16–17 in, 7–12 Nitrogen mustard, history of, 16
1104 Index

No special type (NST) carcinoma, invasive ductal of, Oncogenes, 298 Osteoporosis, 1016–1017
345 DCIS and, 140–142 adjuvant endocrine therapy for, 750
Noble, R., 907 Oncoplastic breast conservation surgery, 576–589 in breast cancer patient, 1028, 1028b, 1029t
Nodal involvement, of early breast cancer, 649–650 crescent, hemibatwing, and batwing techniques, Ovarian ablation
Nodal metastases, lymphatic function and, 590–591 579–581, 580f–582f plus tamoxifen or an aromatase inhibitor,
Nodal recurrences, 809–810 extreme oncoplasty, 586–588, 589f 743–745
Node status, 539–542 general considerations of, 576–578 as type of endocrine therapy, 737
axillary, 540–541 oncoplastic team, 576, 577f Ovarian dysfunction, due to chemotherapy, 1017
internal mammary, 541–542, 541f oncoplastic techniques, 579–586 Ovarian function suppression, 915–916
intramammary, 542 preoperative planning of, 578–579 plus tamoxifen or an aromatase inhibitor,
pathologic assessment of, 542 delayed, 579 743–745
sentinel lymph node mapping for, 541, 541f delayed-immediate, 579 as type of endocrine therapy, 737
supraclavicular, 542 immediate, 578 Ovarian reserve, assessment of, 773–774
Node-negative breast cancer, postmastectomy rationale for, 577, 577f Ovarian suppression, 757
radiotherapy in, 690 reconstructive goals, 577–578, 578f Ovarian tissue cryopreservation and transplantation,
Node-positive disease, undissected axillae after reduction mammaplasty techniques, 581–586 775
sentinel lymph node biopsy and, 690 round block mastopexy (Benelli), 581–586 Ovarian transposition, medical suppression and, role
Nodular adenosis, 128 simple glandular flap techniques, 579, 580f of, 776
Nomograms, 594–595, 602f surgical considerations, 579 Overall survival rates, for radical and modified
Nonaminobisphosphonates (non N-containing), 769 vertical mammaplasty, inframammary excision, radical mastectomy, 447t, 448f
Non–anthracycline-containing regimens, in and central excision techniques, 581, Ovulation, 45
first-generation regimens, 754 583f–584f Oxidative phosphorylation (OXPHOS), in normal
Nonendocrine therapy, for breast pain, 84–85 Oncoplastic surgery, 470, 471f, 485, 488f cells, 285
Nongenetic risk counseling, 1006–1007, 1006b breast reconstruction and, 477–491 Oxytocin, 55
Noninvasive papillary carcinoma, encysted, 142, Oncoplastic techniques, for oncoplastic breast in regulation of mammary gland, 23–24
143f conservation surgery, 579–586
Nonpalpable breast cancer, 646, 646f OncoQuick, in CTC enrichment, 860, 861t P
Nonsentinel lymph node metastasis, risk of, in Oncotype DX, 325, 782 P53 family signaling inhibition, for metastatic breast
micrometastatic sentinel lymph node-positive correlation with, 199–200 cancer, 900t
patients, 633–634 staging of, 539, 539f p53 tumor suppressor, 299–301
Nonsentinel node Oncotype DX assay central role of, 301f
complete staging of, 606, 606t of endocrine therapy, 913 p120, 197, 205, 206f
metastases, predictors of, 626, 626f prognostic and predictive value of, 259–261 Paclitaxel (Taxol), for metastatic breast cancer, 888t,
Nonsteroidal aromatase inhibitor, prior treatment Oncotype DX breast cancer 21-gene assay, 979 889, 891
with, 921–922 Oncotype DX breast DCIS score, 573–574 albumin-bound, 890t, 892
Normal mammary stem cells (MaSC), 288 Oncotype DX test, 747, 755–756 Page’s histologic classification scheme, 265, 266f
19-nortestosterone derivative, 280 Oocyte/embryo cryopreservation, 775, 775t Paget, James, 7, 169
Notch intracellular domain (NICD), 309 Oogenesis, 773 Paget cells, 169
Notch signaling, 309 Oophorectomy, for breast cancer, history of, 15, Paget disease (PD), 185–186, 185f, 458–459
Nottingham Prognostic Index, 262 907 of breast, 169–176
NSABP. See National Surgical Adjuvant Breast and Opera, 4–5 clinical presentation of, 172–174, 173f
Bowel Project. Operable breast cancer differential diagnosis of, 171
NST carcinoma. See No special type (NST) endocrine therapy for, 817–818 hallmark of, 170
carcinoma. optimal preoperative systemic therapy, delivery of, histopathology of, 170–172, 170f–171f, 171t
Nuclear factor kappa-B ligand (RANK-L), activator 816–818 incidence of, 169
of, 804 patient selection for preoperative therapy in, 816 invasive, 171
Nuclear steroid receptor (NSR) superfamily, 272, preoperative chemotherapy, 816–817 management of, 174–175
275f preoperative systemic therapy in, 814, 815b, pathogenesis of, 169–170, 170f
Numb chin syndrome, 943 815f prognosis of, 175–176
Nummular eczema, 179, 179b, 179f principles of preoperative therapy for, 814–818 radiologic findings of, 174
Nutritional therapy, for breast pain, 82–83 rationale for, 814–816 secondary of, 169
response-adapted preoperative chemotherapy, with underlying DCIS, 174
O 817 of nipple, 142
Obesity, breast cancer and, 333–334 treatment monitoring and posttreatment Pagetoid spread, 132
Obscured margins, 341, 343f management, 818 Pain, 1037b
Occult systemic micrometastatic breast cancer, Optimal dye, for intraoperative lymphatic mapping, breast (See Breast pain)
detection and clinical implications of, 858–866 618 postmastectomy, 529
cancer stem cells in, 859 Optimal endocrine therapy, for pre-and screening of, 1036
gene expression profiling of, 858–859 postmenopausal women, 757–758 treatment of, 1036–1037, 1037b
Oeuvres Complètes, 4 Optimal preoperative systemic therapy, delivery of, PALB2, mutations in, 247
Omental flaps, 797–798 816–818 Palbociclib, 826–827, 920
On Disease of the Mammary Areola Preceding Cancer Oral contraceptives and postmenopausal hormone Palpable abnormalities, delayed diagnosis of, 1068
of the Mammary Gland, 7 therapy, breast cancer risk and, 215 Palpable axillary lymph nodes, 614
On the Influence of Inadequate Operation on the Orr incision, 392f, 394f–395f, 649 Palpable versus nonpalpable tumors, feasibility of
Theory of Cancer, 7 Osseous neoplasms, 163 sentinel lymph node dissection for, 613
Oncofertility Osteoclast-mediated bone resorption, Palpation, of breast, 332–333
in clinical practice, 777 bisphosphonates inhibition of, 769 PAM-50, of endocrine therapy, 913–914
for young women with breast cancer, 773–777 Osteolytic bone metastases, 877 PAM50 test, 261
 Index 1105

PAM50-ROR, 839–840 Pericardial constriction, 965–966 Physician-associated errors, 1062

Pamidronate, for bone metastases, 881, 881t, clinical presentation of, 965 Physicians Insurers Association of America (PIAA),
901–902 diagnostic studies of, 965–966, 966f 1057, 1064
Pancoast, Joseph, 8–9 pathology of, 965 Physiology
Panniculitis, 181 pathophysiology of, 965 in embryology to childhood, 37–44
PANVAC vaccine, 930 treatment of, 966 clinical correlates of, 38
Pap smear, for breast cancer, 58 Pericardial effusion, 961–965 accessory axillary breast tissue as, 39f, 41
Papillary carcinoma clinical presentation of, 961–962 amastia as, 41, 42f
mammography of, 346–347, 347f diagnostic evaluation of, 962, 963f–964f newborn nipple discharge as, 43
prognosis for, 255 pathology of, 961 Poland syndrome as, 41–43
Papilloma, 127–128, 128f pathophysiology of, 961, 962f polymastia as, 40–41
nipple discharge due to, 65t recurrent, 965 polythelia as, 38–40, 39f, 40t
PApilloma TRIal against Cancer In young Adults treatment of, 962–963 precocious puberty as, 43–44, 43f
(PATRICIA), 954 Pericardial metastases, 961–966 premature thelarche as, 43, 43f
Parallel design, for phase III clinical trials, 369, Pericardial tamponade hormones in, 37–38
369f low-pressure, 961 morphology of, 37
Parasternal lymph nodes, 34 pathophysiology of, 961, 962f regulatory factors and potential genes in, 38
Parathyroid hormone (PTH), and bone metastases, Pericardial window, for recurrent pericardial effusion, in lactation, 53–55
876 965 clinical correlates in, 55–56
Parathyroid hormone-related peptide (PTHrP), bone Pericardiocentesis, 962–963 delayed onset of lactation as, 55
metastases and, 876 Pericardium, 961 impact on breast cancer risk as, 56
Paré, Ambrose, 4 Periductal abscess, 96–98 lactational success as, 55–56
Parity, breast cancer risk and, 53 causes of, 96–97, 97f hormones in, 53–55
PARP inhibitors, for metastatic breast cancer, 900t factors of, 97 morphology and product of, 53, 54f
Partial breast irradiation, 706–715, 707f presentation of, 96–97, 96f regulatory factors and potential genes in,
accelerated, 706–712, 707f surgical management of, 97–98, 100f–101f 55–56
applicator, 707–709, 709t treatment plan for, 97 in menopause, 56
expert consensus statements in, 710, 712t Periductal mastitis, 88. See also Subareolar abscess. clinical correlates of, 56
external-beam, 709–710, 711t Perthes, Georg, 15 hormones in, 56
future directions of, 710–712 Pertuzumab, 759, 765–766, 765t, 954 morphology of, 56
interstitial, 706–707, 708t in breast cancer therapy, 928t in pregnancy, 50–53
technique of, 706 for metastatic breast cancer, 899 clinical correlates of, 51–53
3D conformal radiation therapy as, 709 PET/CT, for inflammatory breast cancer, 834 hormones in, 51
intraoperative, 712–715 Petit, Jean, 5–6 morphology of, 50–51
additional studies of, 714 Peyrilhe, Bernard, 6 in puberty, 44–50
boost of, 714 Pfahler, George, 15 in clinical correlates of, 47
future directions of, 714–715 Pharmacotherapy, 1044–1045 adolescent, juvenile, or virginal hypertrophy
randomized studies of, 713–714 Phase I trials, 366 as, 47–48
Partial (segmental) mastectomy/lumpectomy, 478 design for, 367 gynecomastia as, 49–50, 49f
trend in, 428t, 432f 3 + 3, 367, 367f, 367t hypogonadotropism as, 50, 50b
Passenger alterations, in carcinogenesis, 299 continual reassessment method as, 367, 367f tuberous breast deformity as, 48–49,
Patey, retrospective trial of, 445t Phase II trials, 366 48f–49f
Patey mastectomy, 392–393 design for, 367–369 hormones in, 44–45
Pathogenesis, multistep, of breast cancer, 59f Fei and Shyr’s, 369, 369t–371t menstrual cycle as, 45–46, 47f
Pathologic complete response (pCR), 927 Fleming’s, 368, 368t morphology of, 44
Pathologic fractures, in bone metastases, 878 Gehan’s, 367–368 regulatory factors and potential genes in,
Patient experience quality measures, 503 Simon’s minimax, 368, 369t–371t 46–47, 46f
Patient Health Questionnaire depression module Simon’s optimal, 368, 369t–371t Pilot studies, 366
(PHQ-9), 1041, 1041t Phase III trials, 366–367 Pituitary adenoma, nipple discharge due to, 66
Patient-associated delays, in diagnosis, 1061–1062 design for, 369–371 Pityriasis rosea, 190
Patient-centered quality measures, 503 crossover, 369–370, 370f Placodes, 37
Patient-reported outcomes (PROs), 503 factorial, 370–371, 371f Plasma cell mastitis, 182. See also Subareolar
Paul of Aegina, 3 parallel, 369, 369f abscess.
PD. See Paget disease. Phillips, Frederick, 16 Plasminogen activator inhibitor (PAI-1), as
Pecquet, Jean, 514 Phosphatase and tensin homolog (PTEN), 298 biological markers, 537–538
Pectoral fascia, 27 Phosphoinositide 3-kinase (PI3K) inhibitors, for Platinum, for metastatic breast cancer, 893
Pectoral group, of axillary lymph nodes, 30, 30f–31f metastatic breast cancer, 900t Platinum derivatives, as cause of chemotherapy-
Pectoral muscles, neurologic innervation of, Phyllodes tumor (PT), 124–129, 127f, 156–158, induced peripheral neuropathy, 1035
388–390, 389f 157f–158f Pleomorphic LCIS, 554f–555f, 555
Pectoral nodes, 516 Physical activity, in breast cancer and lifestyle Pleural catheter, indwelling, 939
Pectoralis major flap, 794–795, 797f factors, 1045 Pleural decortication, 940
Pectoralis major muscle, 24f, 25–26 Physical Activity and Lymphedema (PAL), 493 Pleural effusion, malignant
preservation of, 392 Physician Quality Reporting System (PQRS), 505 causes of, 935t
Pectoralis minor muscle, 24f, 25–26 Physician-associated delays, in diagnosis, 1062–1071 diagnosis and management of, 934–941
Pedicled latissimus dorsi flap, 791f diagnostic workups requested by physicians and, imaging of, 935–936
Pedicled transverse rectus abdominis myocutaneous 1064 immunohistochemistry for, 937
flap, 792–793, 792f intervals of, 1062–1063, 1063f prognosis of, 941
Pentoxifylline (Trental), for lymphedema, 526 specialty training and, 1063–1064, 1064f thoracentesis of, 936–937, 937f
1106 Index

Pleural effusion, malignant (Continued) Postmastectomy radiotherapy (PMRT), 677, Premalignant lesions
treatment of, 937–941 688–692, 783–784 high risk women secondary to, 1008
pleural decortication in, 940 application of randomized trial data in N1 disease LCIS as, 553, 554t
pleural space drainage in, 938–940 of, 688–690 Premature thelarche, 43, 43f
sclerosing agents in, 940–941 benefit of, 689 Premenopausal women, in endocrine therapy,
surgical pleurectomy in, 940 gene expression profiling in, 691 915–916, 915t
thoracentesis for, 938–939 for locally advanced breast cancer, 822 Preoperative Arimidex Compared with Tamoxifen
thoracoscopic surgery in, 940 randomized trials of, 688 (PROACT) trial, 826
tube thoracostomy for, 939 reconstructive surgery and, 692 Preoperative Endocrine Prognostic Index, 783
Pleural fluid, thoracentesis and studies on, special considerations of, 690–691 Preoperative needle localization, imaging-guided,
936–937 in neoadjuvant chemotherapy, 690–691 359, 359f
Pleural metastasis(es), 934–941 in node negative breast cancer, 690 Preoperative planning, for oncoplastic breast
clinical presentation of, 934–935, 935b node-positive disease and undissected axillae conservation surgery, 578–579
diagnosis of, 935–937 after sentinel lymph node biopsy, 690 Preovulatory phase, 57
radiographic findings in, 935–936, 936f tumor biology considerations in, 691–692 Prepectoral lymph node, 31
tissue confirmation of, 936–937 Postmastectomy wound, care of, 492 Prepericardial lymph nodes, 34
pathogenesis of, 934 Postmenopausal women PRESENT trial, 328
prognosis of, 941 bisphosphonate benefit in, 771–772 Primary lesion, 550.e1
tissue biopsies for, 937, 938f in endocrine therapy, 916–917, 917t Primary lymphomas, of breast, 163–168, 164f
treatment of, 937–941 Postovulatory phase, 57 clinical features of, 163
pleural decortication in, 940 Postpericardiocentesis, 963–965 diagnosis and staging of, 163–167
pleural space drainage in, 938–940 Postradiation, reconstruction, 490 natural history and prognosis, 166–167
sclerosing agents in, 940–941 Postregistration trials, 367 pathology, 164f, 165–166, 166f–167f
surgical pleurectomy, 940 Power analysis, in clinical trials, 372–373 patterns of relapse, 167
Pleural needle biopsy, 937, 938f Precocious puberty, 43–44, 43f radiologic features, 163–165
Pleural space drainage, 938–940 Precollectors, 515–516, 517f risk factors/pathogenesis, 165
Pleurectomy, surgical, 940 Predeterminism, biological, theory of, 1075 future directions and conclusion, 168
Pleurodesis, 939–940 Predictive factors, 250, 256 treatment of, 167–168
Plexopathy, brachial, 721 DNA as, 256 Primary site local therapy (PSLT), 868
Ploidy, DCIS and, 140–142 epidermal growth factor receptor family as, 256 benefit of, 870
PMRT. See Postmastectomy chest-wall radiation for metastatic breast cancer, 885 effect of, 870
therapy. steroid receptors as, 256 Primary testicular failure, gynecomastia and, 108
Pneumothorax, after mastectomy, 496 in treatment decisions, 256 Principles and Practice of Surgery, 9
Poland syndrome, 41–43 Predictive markers, development of, 259f Prior neoadjuvant chemotherapy, 811
Pollock, J., 15 “Predictive tests,” 237 Prior radiation therapy, 810, 810t
Polychemotherapy, for breast cancer, 325 Predictor analysis of microarray 50 (PAM50) assay, Prior systemic therapy, 810–811, 810t
Polymastia, 20, 40–41, 178 755 PRL. See Prolactin.
Polymerase chain reaction (PCR), 63 Preeclampsia, breast cancer and, 215 Process, of care, 503
Polysomy, definition of, 203 Pregabalin, 1026 Progesterone, 55
Polythelia, 20, 38–40, 39f, 40t, 178 Pregnancy breast pain and, 81
Pompeii, surgical instruments from, 2 after breast cancer, 1017–1018 for mastalgia, 86
“Popcorn-like” calcifications, 344, 344f breast density during, 340 in regulation of mammary gland, 23–24
Portmann classification, for staging, 543, breast physiology in, 50–53 Progesterone analogs, 1026
543t clinical correlates of, 51–53 Progesterone receptor(s) (PRs), 280, 291–292
Positive Node Endocrine Responsive Breast Cancer, hormones in, 51 historical perspective of, 198
259 morphology of, 50–51 in locally advanced breast cancer, 820
Positive sentinel lymph node, 596 breast tumor of, 126 monoclonal antibodies for, 201t
completion axillary dissection and, in cancer patients and survivors, 776–777 as primary tumor characteristics, 535
678–680 lactational bloody nipple discharge during, 66 status, predictive power of, 908
without a completion axillary dissection, mammary glands during, 22–23, 23f tissues of, proper technique for processing, 387
677–678 sentinel lymph node dissection during, 612 Prognostic factor(s), 250–257
Positron emission tomography (PET) CT imaging, Pregnancy-associated (gestational) breast cancer adjuvant therapy and, 250
for axillary metastasis of unknown primary, BRCA mutations and, 998 application to individual of, 250
1000–1001 definition of, 993 axillary lymph nodes, 251–254
Posterior circumflex humeral arteries, 26 delayed diagnosis of, 1069–1070 biological markers, 531–542, 536f, 538f
Posterior intercostal arteries, 24f, 25 diagnostic evaluation and staging during bone marrow micrometastases as, 536–537
Posterior mediastinal lymph nodes, 35 pregnancy, 993–995 cathepsin D as, 537–538
Posterior suspensory ligaments, 28 breast biopsy, 994–995 circulating tumor cells (CTCs) as, 537
Postmastectomy chest-wall radiation therapy imaging studies, 994 molecular profiling as, 539
(PMRT), 978 pathologic findings, 995 molecular subtype as, 538, 538f
Postmastectomy pain syndrome, 498, 529, 529f epidemiology of, 993 plasminogen activator inhibitor as, 537–538
Postmastectomy radiation prognosis and historical perspective, 993 tumor markers as, 537–538
after NAC and mastectomy, 730 staging of, 993–995 urokinase plasminogen activator as, 537–538,
guideline statements for, 728–729 therapeutic abortion for, 998 537f
in inflammatory breast cancer, 837–838 treatment of, 995–998 clinical, 531–542
locoregional recurrence rate without, 728, 728t, radiation therapy for, 997–998 estrogen and progesterone receptors as, 535
731t surgery for, 995–996 HER2/neu expression as, 535
rationale for, 728 systemic chemotherapy for, 996–997, 997t histopathologic features as, 534–535
 Index 1107

Prognostic factor(s) (Continued) Psychosocial intervention, 1044–1045 Quantitative multiplex methylation-specific PCR,
primary tumor characteristics as, 532–536 timing of, 1044 ductal lavage and, 63–64
tumor grade as, 534 types of, 1044–1045 Quantitative risk assessment, 1004
tumor growth rate and proliferation as, Psychosocial issues, in breast cancer survivors, 1053
535–536 Psychosocial screening, 1040 R
tumor histology as, 534 PT. See Phyllodes tumor. Rab and His Friends, 7
tumor location as, 533–534 pT4b disease, 171 Race, as prognostic factor, 255–256
tumor size as, 532–533, 533f, 533t PTEN, mutation in, 247–248 Race, in breast conserving surgery and radiation,
clinically established, in breast cancer, 250–257 PTEN hamartoma tumor syndrome (PTHS), 696
age and race as, 255–256 247–248 RAD51C, mutation in, 248
histologic factors as, 254–255 Pubertal gynecomastia, 105, 105f RADCOMP breast proton versus photon study,
nodal status as, 250 Puberty 723–724
tumor size as, 250, 254 breast physiology in, 44–50 Radial nerve, 27, 27f
lymph node status as, 539–542 in clinical correlates of, 47 Radial scar, 90, 123–124, 123f, 271
axillary, 540–541 adolescent, juvenile, or virginal hypertrophy mammography of, 352
internal mammary, 541–542, 541f as, 47–48 Radiation, complication and management of,
intramammary, 542 gynecomastia as, 49–50, 49f 716–725
pathologic assessment of, 542 hypogonadotropism as, 50, 50b Radiation dermatitis, 180
sentinel lymph node mapping for, 541, 541f tuberous breast deformity as, 48–49, Radiation exposure, and bilateral breast cancer,
supraclavicular, 542 48f–49f 969
molecular, for breast carcinoma, 258–263 hormones in, 44–45 Radiation on fertility, impact of, 774
pathologic, 531–542 menstrual cycle as, 45–46, 47f Radiation pneumonitis, incidence of, 722, 722t
Prognostication, for metastatic breast cancer, morphology of, 44 Radiation sensitizers, 955
885–886 regulatory factors and potential genes in, Radiation therapy (RT), 324
Programmed death ligand-1 (PDL-1), 305, 931 46–47, 46f accelerated partial breast irradiation for, 706–712,
Programmed death-1 (PD-1), 305, 329 precocious, 43–44, 43f 707f
Progression, psychologic distress due to, 1043 Public quality measurement reporting, future of, applicator, 707–709, 709t
Proinflammatory cytokines, 319 506–507 expert consensus statements in, 710, 712t
Prolactin (PRL) Puerperal/lactational mastitis, 182 external-beam, 709–710, 711t
breast pain and, 81 Pulmonary complications, 721–722, 721f future directions of, 710–712
in regulation of mammary gland, 23–24 Pyoderma gangrenosum (PG), 189 interstitial, 706–707, 708t
Prolactinemia, nipple discharge due to, 66 technique of, 706
Proliferation marker, 204–205, 205f Q 3D conformal radiation therapy as, 709
Proliferative breast disease, 118–119, 119b, QOL. See Quality of life. with breast conserving surgery, 472–475
119f–120f Qualitative risk assessment, 1004, 1005b, 1005t adjuvant systemic therapy as, 700
complex fibroadenoma, 267–269, 270t Quality breast-conserving surgery without, 703–704
hormone replacement therapy in, 271 breast-specific, measures, 504t, 506f, 511 characteristics and management of local failure
Prone breast board, 668 of care, 500 in, 702–703, 703t
Prophylactic mastectomy creation of, measures, 507 with mastectomy, comparing breast conserving
bilateral, risk reducing surgery, 246 databases for, and clinical outcomes research, surgery, 693–694
contralateral, 453–455 501–502 patient selection for, 694–700
Prophylactic surgery, in bone metastases, 878 diagnostic errors of, 500 adjuvant systemic therapy in, 700
Prosigna, 781–782, 913–914 future of public, measurement reporting, clinical factors of, 694–696
Prosigna breast cancer prognostic gene signature 506–507 genetic factors in, 696
assay, 261 gaps of, 499, 501 gross multifocal/multicentric disease in,
Prospective cohort study, 364, 364f of health care, 499 696
Protein α lactalbumin, 932–933 improve, 509–511, 511t margin status in, 697–698, 698t
Proteomic technologies, ductal lavage and, 64 measures, 499, 502–503 pathologic factors in, 696–699
Proton therapy, 668–669, 682–687, 683f, 710, 711t outcomes of, 503 patient age in, 695
PRs. See Progesterone receptor(s). patient safety, 500 race in, 696
Pseudoangiomatous stromal hyperplasia (PASH), 90, reporting systems in public sector, 505–506 radiation boost in, 699–700
127, 159, 159f stakeholders for, 499–500 surgery in, 699
Pseudogynecomastia, 104 surgical, measurement, 500 tumor size in, 695–696
Pseudohermaphroditism, gynecomastia and, 108 value and, 500 tumor subtyping in, 698–699
Psoriasis, 189, 189f Quality cycle, 509 radiation boost as, 699–700
Psychiatric approaches, for refractory mastalgia, 86 Quality data, analyzing, 508 surgery as, 699
Psychoeducation, 1045 Quality measure (QM), 503–505 timing of, 701–702
Psychological distress, in breast cancer challenges in, 512 treatment factors in, 699–700
in cancer survivorship, 1043 compliant, 510f in breast reconstruction, 490–491
in diagnostic process, 1042 creation of, 507 for cardiac dysfunction, 1052
due to adjuvant therapy, 1042–1043 importance of, 507 contraindication of, 468
due to breast biopsy, 1042 list of, 507–508 dose of, 475
due to recurrence or progression, 1043 risk of, 511–512 for inflammatory breast cancer, 837–838
due to surgery, 1042 use of, 508 intraoperative, 712–715, 713t
hereditary, 1041–1042 Quality of life (QOL) additional studies of, 714
sources of, 1041–1043 in adjuvant endocrine therapy, 750 boost of, 714
Psychosocial aspects, of breast cancer, 1039 outcomes, lifestyle intervention with, 1046–1047 future directions of, 714–715
Psychosocial concerns, in breast cancer, 1019–1020 psychosocial intervention to improve, 1044–1045 randomized studies of, 713–714
1108 Index

Radiation therapy (RT) (Continued) Radioguided sentinel lymphadenectomy, surgical Random periareolar fine-needle aspiration (RPENA),
for locally advanced breast cancer, 726–735 technique for, 623–624 64
followed by adjuvant chemotherapy, 729 Radiolocalization Random permuted block randomization, 372
for inoperable LABC, 730 identification of the sentinel node by, 607 Random-digit table, 372
neoadjuvant chemotherapy followed by, 729 lymphatic mapping with isotopes and, 622–624 Randomization
prognostic factors and future directions of, Radiopharmaceuticals, 880 biased coin, 372
731–732 Radiosurgery, stereotactic, 950–952 complete, 372
rationale for postmastectomy radiation in, 728 Radiotherapy. See also Radiation therapy. process, in clinical trials, 371–372
rationale for use of systemic therapy, 727–728 anatomic considerations of, 664, 665t random permuted block, 372
lymphedema from, 522, 522t axillary, 597–598, 597t replacement, 372
versus no radiation therapy, 473–474 axillary dissection, positive sentinel node Randomized controlled studies, 366–367
during pregnancy, 997–998 completion and, 678–680 design for, 369–371
sequencing of, 474 without completion of, 677–678 crossover, 369–370, 370f
technique of, 474–475 biological basis of, of breast, 663–670 factorial, 370–371, 371f
thoracic, risk-based screening after, 1009, 1009b for bone metastases, 879–880 parallel, 369, 369f
treatment, length of, 475 postoperative, 879–880 Rapamycin, 826–827
trends and patterns of care, 1971 to 1984, radiopharmaceuticals of, 880 Reach out to Enhance Wellness (RENEW) trial,
422–423, 424f retreatment with, 880 1047
Radiation Therapy Oncology Group (RTOG), 664, side effects of, 880 Récamier, Joseph, 8
946 cardiac avoidance in breast, 667–669 Receptor proteins, DCIS and, 140–142
fractionation regimens of, in brain metastases, 947 ductal carcinoma in situ and, 671–676 Reconstructed breast, recurrence in, 985–986
hyperfractionated, 948 after mastectomy, 676 Reconstruction, 477–491
74-02 trial, for bone metastases, 879 randomized trials on, 671–673, 672t with acellular dermal matrix, 480–481
trial 97-14, for bone metastases, 879 recurrence and results of salvage treatment in, considerations of, 414–421, 416f–417f
Radiation-related cardiac mortality, risk of, 723 675–676 factors influencing, 417–421
Radical mastectomy, 779 tamoxifen and, 674–675, 675t with fat grafting, 485–486
Annual National Cancer Database (NCDB) tools to predict risk on, 674 history of, 17–18, 18t
Benchmark Reports in, 436f external-beam techniques and considerations in, immediate breast, 442
evolution of technique for, 391 664–667 with ipsilateral transverse rectus abdominis
extended, 437 history of, 14–15 myocutaneous flaps, 410f
Halsted, 422–442 for metastatic disease, in intact breast primary, from mastectomy, 478
historical aspects for development of, 422 868t, 870 multivariate analysis of factors influencing, 420t
evolution of, 422 modalities of, 663–664 myocutaneous flaps for, 481–485
Halsted in, 422 patient selection for, 677–680 transverse rectus abdominis (See Transverse
Meyer in, 422 postmastectomy, 688–692 rectus abdominis myocutaneous (TRAM)
immediate breast reconstruction in, 442 application of randomized trial data in N1 flap)
indication for, 436–437, 437b disease of, 688–690 nipple, 490
for large breast lesions, 438f benefit of, 689 nipple-areola, 413f
modified (See Modified radical mastectomy) gene expression profiling in, 691 oncoplastic surgery as, 485
percentage of breast cancers receiving, 433f randomized trials of, 688 opposite breast considerations in, 486–490
principles of, 422 reconstructive surgery and, 692 outcome for locally advanced breast cancer with,
skin excision with, 397 special consideration of, 690–691 420t
standardized, evolution of, 9–12, 11f, 11t in neoadjuvant chemotherapy, 690–691 overview of, 415–417
technique for, 437–442 in node-negative breast cancer, 690 from partial mastectomy/lumpectomy, 478
drainage catheter in, 441–442 node-positive disease and undissected axillae postradiation, 490
exposure of the superolateral aspect of, 439f after sentinel lymph node biopsy, 690 principal deterrent for, 417
flap closure in, 441 tumor biology consideration in, 691–692 reconstructive surgical methods in, 478–491,
immediate breast reconstruction in, 442 radiobiological considerations of, 664 479f–482f
incisions in, 438 regional nodes and, 677–687 role of, in breast cancer treatment, 477–478
large skin flaps in, 442f digitally reconstructed radiograph (DRR) in, satisfactory, 415
lateral (axillary) nodal group, swept of, 440 681f of skin conservation mastectomies, 409f
patient positioning in, 437 patient selection for, 677–680 timing of, 490–491
position of the first assistant in, 437–438, 438f techniques for, 680–687 tissue expansion/implants in, 479–480
prepped, 437–438 for supraclavicular region, 677–678, 682f–683f TRAM flap in (See Transverse rectus abdominis
residual margins in, 441f techniques of, 663 myocutaneous (TRAM) flap)
split-thickness skin graft in, 442f Radiotherapy Comparative Effectiveness Consortium Reconstructive goals, for oncoplastic breast
superomedial dissection in, 440f (RADCOMP) survey, 679 conservation surgery, 577–578, 578f
thoracodorsal nerve in, 440 Railroad track, calcifications and, 348, 349f Reconstructive surgery, postmastectomy radiotherapy
thoracodorsal neurovascular bundle in, Raloxifene, 276, 910 and, 692
440–441 for breast cancer, 221–222, 558 Rectus abdominis transposition and free flaps, 791,
typical position for draping patient in, 437f clinical data with, 230 791f
variants of, 392f for osteoporosis, 910, 1017 Rectus musculocutaneous flaps, 793–794, 794f
Radiculopathy, 1035 recommendation of, 235–236 Recurrence
Radiofrequency ablation, 656–657, 656f trial, study of, 230–231 after breast conserving therapy, 986–989, 987f
Radiographic-detectable breast cancer, 1057 STAR results after 81 months of follow-up, local
Radiographic-undetectable breast cancer, 1057 230–231 after skin-sparing mastectomy, 396–397
Radioguided occult lesion localization (ROLL), 384, STAR trial and potential population impact, tumor volume and, 397
469, 613 231 locoregional, surveillance for, 1011–1014
 Index 1109

Recurrence (Continued) Risk assessment models Screening mammograms, 1069

psychologic distress due to, 1043 based on family history and genetic factors, Screening mammography, 334, 337, 643
radical mastectomy and recurrence after breast 1005–1006 craniocaudal view of, 337, 338f–339f
conservation therapy in, 424–425, 427f based on nongenetic factors, 1004–1005, 1005b in follow-up care, 1013
in reconstructed breast, 985–986 Risk aversion, 511–512 importance of compression in, 337
risk factors for, 1011 Risk factors, for locoregional recurrences, 1011 mediolateral oblique view of, 337, 338f
Recurrence score, 154 Risk management Scultetus, 4–5, 5f
Recurrent disease, repeat immunohistochemical in clinical setting, 1007 Sebaceous glands, 21
studies on, 200–201 risk reduction options based on level of risk in, Seborrheic dermatitis, 188–189, 189f
Recursive Partitioning Analysis Prognostic Classes, 1007 Seborrheic keratosis, 183
946t risk-based screening recommendations in, 1009, Secondary lesions, 550.e1
Reduction mammaplasty, 486–489 1009b Secondary testicular failure, gynecomastia and,
Reduction mastopexy lumpectomy, 471f Risk-based screening recommendations, 1009, 108–109
Regional node irradiation (RNI), 678 1009b Secretory calcifications, 348–349, 349f
Regional nodes Roentgen, Wilhelm, 14–15 Secretory carcinoma, 150
in MBC, management of, 977–978 Rotter nodes Secretory phase, in menstrual cycle, 45, 47f
radiotherapy and, 677–687 anatomy of, 30f–31f, 31–32 Selective estrogen receptor downregulator (SERD),
digitally reconstructed radiograph (DRR) in, topographic surgical, 390 272, 911–912
681f Round block mastopexy (Benelli), 582, 585f molecular mechanism of, 274f, 276
patient selection for, 677–680 RT. See Radiation therapy. Selective estrogen receptor modulators (SERMs),
techniques for, 680–687 RTOG. See Radiation Therapy Oncology Group. 272, 908–910
3D conformal radiation as, 681, 681f Ruptured epidermal inclusion cyst, 181 history of, 907–908
multifield IMRT as, 681, 682f–686f RxPONDER Trial, 259, 782 indications and contraindications, for risk
proton therapy as, 682–687, 683f reduction with, 228–229, 228b
Regional recurrence. See also Locoregional S in lobular carcinoma in situ and atypical
recurrence. S classification system, 595–596 hyperplasia, 225–227
after mastectomy, 983 SA. See Sclerosing adenosis. molecular mechanism of action of, 274f, 276,
Regulatory CD4+ helper T cells (Tregs), “Saddle anesthesia,” 944 277f
924–925 Safety, in surgery and diagnostic errors, 500–501 raloxifene as, 910
Rehabilitation, 1031–1038 Saint Agatha, 2–3 tamoxifen as, 908–910
cognitive dysfunction, 1038 Salivary gland-type breast carcinoma, 150 toremifene as, 910
deconditioning, 1031–1032, 1032b Salomon, A., 17 as type of endocrine therapy, 737
exercise in, 1037 Salpingo-oophorectomy, bilateral, risk reducing Senile gynecomastia, 105, 106f
fatigue, 1032–1033, 1032b surgery, 245–246 SENTINA trials, 614–615, 786
neuropathy, 1034–1036 Salvage mastectomy, 437 Sentinel lymph node(s) (SLNs), 604, 977
pain, 1036–1037 treatment for local recurrence after breast definition of, 607–609
upper quadrant dysfunction, 1033–1034 conserving therapy, 988 dissection, recommendations and levels of
vocational, 1038 Samarium-153 (Sm153), 880 evidence for, 611t
Reifenstein syndrome, gynecomastia and, 109 Sample collection, for nipple discharge, 71 false-negative, 625–626
Reirradiation, 880 Sample preparation, for nipple discharge, 71 frequency of, 616f
Relationship issues, in breast cancer survivors, Sample size determination, for clinical trials, history of, 604
1052–1053 372–373 hottest node, 624
Renaissance, history of breast cancer therapy in, “Sandwich sign,” 188 hypothesis, validation of, 633
4–5, 5f Sanger sequencing, on breast cancer genetics, identification of
Replacement randomization, 372 240–241 combined technique of vital dye and
Reproductive factors, of breast cancer, 209–211 Sarcoidosis, 190 radioisotope for, 607
Residual cancer burden (RCB), 786–787 Sarcoma(s), breast, 156 by preoperative lymphoscintigraphy and
Response-adapted preoperative chemotherapy, Satellite skin metastasis, 195, 195f intraoperative radioguided surgery, 607
817 Scalene lymph node biopsies, 542 by radiolocalization, 607
Retinoblastoma gene (RB), 284 Scapula, winged, 389f internal mammary, management of, 615
Retromammary bursa, 20, 22f Scapular group, of axillary lymph nodes, 30, 30f–31f lymphatic territories of, 517–518, 519f–520f
Retropectoral pathway, of lymphatic drainage, 30f, Scapulothoracic bursitis, trigger point injections for, metastases, histopathology images of, 625f
32 86, 86f multicenter lymphatic mapping trials for,
Retropectoral routes, of lymphatic drainage, Scar-associated breast cancer, delayed diagnosis of, 609–610
390 1071 pathologic evaluation of, 636
Retrospective cohort study, 364–365, 365f Scars, radial, mammography of, 352 positive, 604
Reverse transcription PCR (RT-PCR), in CTC Schinzinger, Albert, 15, 907 predictors of, metastases, 615–618
detection, 862 Schultes, Johann, 4–5 H&E positive, 617–618
Reverse-transcriptase polymerase chain reaction Schwannoma, 162 radiation treatment of axilla, 618
(RT-PCR), 257 Scientific acceptability, 507 removed, numbers of, 616, 617t
Rhabdomyosarcoma (RMS), 162–163 Scintimammography, 335 sentinel node, 615–616
Rhazes, 4 Scirrhus, 5 significance of micrometastases, 616–617
Rib fracture, 721 Sclerosing adenosis (SA), 90, 121–122, 123f tumor size, 615–616
Ribociclib, 826–827 Sclerosing agents, for pleural metastases, 940–941 procedure, staging the axilla and, 854–855
Risk assessment, 1004 Sclerosing lesions, localized, 121–124 radioguided dissection, combined blue dye and,
in clinical setting, 1006 Sclerotherapy, for recurrent pericardial effusion, 965 624f
qualitative, 1004, 1005b, 1005t Scottish Adjuvant Tamoxifen trial, 918 radiopharmaceutical for, 622
quantitative, 1004 Screening, for distress, 1040–1041, 1040f reduction in the rate of false-negative, 633
1110 Index

Sentinel lymph node(s) (SLNs) (Continued) Sentinel lymphatic channel, 44 Skin-sparing mastectomy (SSM), 396–414, 411f,
surgery for, micrometastases, 635 Sentinel node (SN). See Sentinel lymph node(s) 649, 651f
vital dye for (SLNs). breast cancer after, 990–991
combined technique of, 607 Serial sections (SS), for axillary lymph node, 631 flap elevation in, 400–414
global experience with, 607–609 SERM Chemoprevention Trials, summary of, 225, incision design for, 400, 408f
Sentinel lymph node biopsy (SLNB), 31–32, 1033. 226t indications for, 399
See also Sentinel lymphadenectomy. SERM-ER complex, 276 rationale for, 396
axillary recurrences, after mastectomy and, 983 SERMs. See Selective estrogen receptor modulators. recurrence after, 396–397
for DCIS, 574 Seroma, after mastectomy, 493–496, 495f, technical aspects of, 399, 400f, 404f, 413f
enhanced pathology in, 633–634 495t–496t technical features of, 399b
evolution of simple mastectomy with, 449 Sertoli cell tumors, gynecomastia and, 107 SLNB. See Sentinel lymph node biopsy.
history of, 14 Servetus, Michael, 4 SLND (sentinel lymph node dissection). See Sentinel
identification of, 614t 70-gene assay (MammaPrint), of endocrine therapy, lymph node biopsy; Sentinel lymphadenectomy.
lymphedema and, 515t, 521 914 SLNs. See Sentinel lymph node(s).
for node-negative patient, 828 70-gene signature, for staging, 539 Small breast cancer, axilla in, selective management
for Paget disease, 175 Sexual dysfunction of, 590–603, 591f
during pregnancy, 995 adjuvant endocrine therapy and, 749 Smith, Edwin, 1, 2f
role of, in patients with LABC, 785–786 in breast cancer survivors, 1018–1019 Smoking, breast cancer and, 217
Sentinel lymph node dissection (SLND). See Sexual health, in breast cancer survivors, 1052–1053 Smooth muscle neoplasms, 192, 192f
Sentinel lymphadenectomy. Shape, of mass, 340–341, 342f SN (sentinel node). See Sentinel lymph node(s)
Sentinel lymph node (SLN) mapping Sheehan syndrome, 56 (SLNs).
accuracy of, 541 Shifting paradigm, in SLN micrometastases, 635, Social work services, 1045
clinical significance of, 541, 541f 635t Society of Surgical Oncology and the American
in staging, 541 SI, 595–596 Society for Radiation Oncology, 648
technique for, 541 Signal transduction pathways, 273f Society of Surgical Oncology Position Statement,
Sentinel lymphadenectomy, 593–594. See also SIII, 595–596 455b
Sentinel lymph node biopsy. Silicone, of implant breast Sociodemographic factors, of breast cancer,
accuracy and prognostic value of, 607 delayed diagnosis with, 1071 208–209
anesthetic considerations for, 621 history of, 17 Solitary metastases, 802–807
applications of, 614–615 Silicone granulomas, 989, 990f bone, 804–805
for breast cancer, 604–630 Silvadene therapy, 621 brain, 805–806
clinical, pathologic, and technical aspects of, Simon’s minimax design, for phase II clinical trials, liver, 802–803
610–618 368, 369t–371t lung, 803–804
dissection technique for, 621–622, 622f Simon’s optimal design, for phase II clinical trials, Somatic alterations, 298
for ductal carcinoma in situ and ductal carcinoma 368, 369t–371t Sorafenib, for metastatic breast cancer, 900
in situ with microinvasion, 612–613, 613t Simple curtailment, 375 “Sorgius node,” 604
effect of isotope filtration for, 622 Simple glandular flap techniques, 579 Spanish Multicenter Clinical Trial, 635, 636f
evolution of dye-directed, 604–606 Simple mastectomy, 448–457. See also Total Special types, of invasive breast cancer, 255
histopathologic staging by, 605, 605t mastectomy. Specifications, of quality measure, 503
prospective validation of, 605–606, 606t evolution of, 449 Specimen handling, 639–642
surgical feasibility of, 605 indications for, 455b Spectrum hypothesis, 316–317, 631, 643
global experience with, 607–609, 608t–609t operative techniques for variations of, 458–460 Spiculated margins, 341, 343f
guidelines for, 627 prophylactic, 455–456 Spinal cord compression, in bone metastases, 877
injection site for, 622–623 prospective trials for, 449–453 Spiritual services, 1045
intraoperative gamma-probe detection, 623 Edinburgh Royal Infirmary—Cardiff trial as, Split reduction technique, 583–586, 586f–588f
for invasive carcinoma, 612 450t–451t Spontaneous copious nipple discharge, 67f
learning curve of, 627 Manchester Regional Breast study as, 451t Spot compression, during mammography, 339, 340f
morbidity of, 626–627, 627t National Surgical Adjuvant Breast and Bowel Sprengel, 457
operative procedure and, 614 Project, 451–453 Squamous cell carcinoma, 151, 153f, 193, 193f
patient selection criteria for, 610–612, 610t–611t survival results of, 449t Squamous cell carcinoma in situ (SCCIS), 172
age in, 611 retrospective studies of, 448 SRS. See Stereotactic radiosurgery.
body habitus in, 612 surgical techniques for, 458–459 SSM. See Skin-sparing mastectomy.
gender in, 611–612 survival rates for, 449t, 450f St. Gallen, National Comprehensive Cancer
pregnancy and lactation in, 612 Six colored inks, for excised breast specimens, 648, Network and, 752
previous breast or axillary surgery in, 612 648f St. Gallen International Expert Consensus Group,
previous excision in, 612 Skin bridge, with skin-sparing mastectomy, 400 324
preoperative chemotherapy for, 614–615, 614t Skin calcifications, 348–349 St. Paul Fire and Marine Insurance Company, 1059
prospective study of, 607, 607t Skin excision Stage groupings, 548, 548t, 549f
radioguided, surgical technique for, 623–624 effect on local recurrence, 397 Stage IV breast cancer, 456
randomized clinical trials for, 627–630 with modified radical mastectomy, 398 Staging
technical considerations for, 618 with radical mastectomy, 398–414 clinical factors of, 532, 532t
general technical, 618, 619t–620t Skin flap development, 457–458 current system for, 542–544
tumor features of, 612–614 Skin flap mobilization, 414 histopathologic grade in, 548, 548t
feasibility of, for palpable, 613 Skin flaps. See Flap(s). specific stages in, 545–548
multifocal or multicentric disease, 613, 613t Skin grafts, tube, 478–479, 479f–480f M stage as, 548, 548t
palpable axillary lymph nodes, 614 Skin incisions, 458 N stage as, 546–548, 546t–547t
type of carcinoma, 612–613 Skin island, with skin-sparing mastectomy, 400 T stage (tumor size) as, 545–546, 545t
used to stage axilla, 650 Skin telangiectasias, 720, 720f stage groupings in, 548, 548t, 549f
 Index 1111

Staging (Continued) Study of Tamoxifen and Raloxifene (STAR) trial, Surgical therapies (Continued)
evolution of system for, 542–544 910 for modified radical mastectomy, 422–423,
Columbia Clinical Classification in, 543, 544t Subareolar abscess, 92, 180–181, 180f 432f
Manchester system in, 543, 543t Subareolar plexus, 30f, 33 for radical mastectomy, 422–423
Portmann classification in, 543, 543t Subclavian trunk, 517 for radical mastectomy and recurrence after
TNM system in, 544 Subclavicular group, of axillary lymph nodes, 30f, breast conservation therapy
triple biopsy in, 543 31–32 in local recurrence, 424–425, 427f
molecular, 542 Subclavius muscle, 26, 27f survival after, 426f
past, present, and future of, 531 Subcostalis muscle, 25 for total mastectomy, and lumpectomy,
primary tumor characteristics of, 532–536 Subcutaneous mastectomy, 990–991 424–425, 426f
estrogen and progesterone receptors as, 535 Subpectoral implants, 481 by type of operation and stage distribution,
HER2/neu expression as, 535 Subscapular artery, 26 425, 427t
histopathologic features as, 534–535 thoracodorsal branch of, 28 by type of treatment and stage distribution,
tumor grade as, 534 Subscapular group 425–426, 428t
tumor growth rate and proliferation as, of axillary lymph nodes, 30, 30f–31f in use of radiotherapy, 424f
535–536 of axillary nodal groups, 390 trends and patterns of care, 1985 to 2002,
tumor histology as, 534 Subscapular nodes, in lymphedema, 517, 518f 427–430
tumor location as, 533–534 Sunitinib, for metastatic breast cancer, 900 in Canada, 430, 433t
tumor size as, 532–533, 533f, 533t Superficial lymphatic vessels, 34 in first-course surgery, all diagnoses, all
prognostic factors in (See Prognostic factor(s)) Superior epigastric artery, 791 hospitals, all states, 434t–436t
Stakeholders, for quality measurement, 499–500 Superior gluteal artery perforator (SGAP), 485 frequency of surgical procedures
Standardization of Breast Radiotherapy (START) Supernumerary breasts. See Polymastia. by region, 429, 430t
pilot trial, 700 Supernumerary nipples. See Polythelia. by stage distribution, 429t
Staphylococcus aureus, breast abscess associated with, “Supervoltage” radiotherapy, in the treatment of modified radical mastectomy, and radical
93–94 LABC, 780 mastectomy, 429, 432f
Starvation, recovery from, gynecomastia and, 108 Supine breast board, 668 in partial (segmental) mastectomy, 428t, 432f
Static original determinism, 321 Supportive psychotherapy, 1045 in relative survival of, 431t–432t
Stem cell(s) Suppression of Ovarian Function Trial (SOFT), 744, by stage distribution, 427t
in breast cancer, 309–314, 309f 744f, 745t, 783, 821–822 by year of diagnosis, 428t–430t
in breast development and cancer, 308–314 Supraclavicular lymph node metastasis, recurrence trends in selection of mastectomy therapies, 2000
immune system and, 312–313, 312f in, after mastectomy, 983 to 2016, 430–435
key signaling pathways of, 310–311 Supraclavicular lymph nodes, prognosis of, 542 in Japan, 433–434, 434f
mammary, regulatory pathways, 309 Supraclavicular nerve, 29 Surveillance
markers of, 308–310, 310t–311t Supraclavicular region, radiotherapy for, 677–678 for locoregional recurrences or new primary
in normal breast, 308–309 Supraclavicular space, 983 disease, 1011–1014
tumor microenvironment and, 312–314 “Supraradical mastectomy,” history of, 13 in male breast cancer, 980
Stereotactic core biopsy, 566 Supreme thoracic artery, 26 Survival
Stereotactic core needle biopsy, 380t, 381–382, 381f Surface anatomy, of breast, 20–21 delayed diagnosis and, 1071–1079
Stereotactic radiosurgery (SRS), 950–952 Surface enhanced laser desorption and ionization studies showing an adverse effect of,
randomized trials for, 951t time of flight (SELDI-TOF), 64 1071–1075
versus surgery, 950–951 Surgeon, role of, in cardiac avoidance, 667, 667f studies showing no effect of, 1075–1079
and whole-brain radiation therapy, 951–952 Surgical anatomy, topographic, 388–391 disease-free, 426f
Sterile skin preparation, for modified radical lymphatic drainage and routes for metastases in, by stage, type of operation, and type of adjuvant
mastectomy, 457 390–391 therapy, 422–423, 425t
Steroid hormone receptor versus ischemia time, neurologic innervation of pectoral muscles in, Survivorship, breast cancer, 1049–1056
388t 388–390, 389f cancer risk and management strategies and,
Steroid receptor. See also Estrogen receptor(s); vascular distribution in, 390 1054–1055, 1054b
Progesterone receptor(s). Surgical approaches, for refractory mastalgia, 86 cardiac dysfunction and, 1051–1052
in breast cancer, 272–281 Surgical biopsy, 380t, 382–385, 383f care, development of, 1055
androgen receptor as, 280 Surgical excision, of primary tumor, 456–457 cognition in, 1050–1051
estrogen receptor as, 272–280 Surgical excisional biopsy, 336 fatigue in, 1049–1050, 1050b
historical perspective on, 272–274 Surgical management. See also Lumpectomy; fertility and, 1053–1054
molecular mechanism of, 274–276 Mastectomy. imaging and, 1055
and tamoxifen, 272 after neoadjuvant chemotherapy, 852–854 menopause and, 1053–1054
progesterone receptor as, 280 of breast cancer, 986 psychosocial issues and healthy lifestyle in, 1053
as predictive factors, 256 for inflammatory breast cancer, 837 sexual health, body image, and relationship issues
Stewart incision, 392f, 394f, 396, 407f Surgical quality measurement, 500 in, 1052–1053
Stewart-Treves syndrome, 514 Surgical therapies Survivorship care planning, 1022
STK11, mutation in, 248 historical aspects of, radical mastectomy in, Survivorship issues, in male breast cancer, 980
Stochastic curtailment, 375 422 Suspensory ligament of axilla, 28
Stochastic model, of tumor heterogeneity, 309 Halsted in, 422 Suspensory ligaments of Cooper, 21, 28
Stockholm radiotherapy trial, 598 Meyer in, 422 Sweat glands, 21
Stone, William, 15 trends and patterns of care, 1971 to 1984, Swedish DCIS trial, 569
“Strategic Science,” 202 422–426 Swedish Multicenter Cohort Study, 610
Stroke, in breast cancer survivors, 1020 in application of systemic chemotherapy, 424f “Swiss cheese” pattern, 181
Stromal lymphatics, 53 for five-year survival rate by stage, type of Syme, James, 7
Strontium-89 (Sr89), 880 operation, and type of adjuvant therapy, Synchronous contralateral breast cancer, 970
Structure, of care, 503 422–423, 425t “Systemic hypothesis,” 316
1112 Index

Systemic therapy Taxanes, 952–953 Total mastectomy

induction, 871–872 for breast cancer, 781–782 evolution of technique for, 391–392
Japan Clinical Oncology Group (JCOG) in, 872 in breast cancer therapy, 928t incision for, 393–394
locoregional therapy before, 872–873 as cause of chemotherapy-induced peripheral skin-sparing (See Skin-sparing mastectomy)
neuropathy, 1035 TP53, 284–285
T combination of, other chemotherapeutic agents, mutation in, 247
T stage, in TNM system, 545–546, 545t 892–893 Tracheobronchial lymph nodes, 35–36
Tachycardia for locally advanced breast cancer, 822–823 TRAM flap. See Transverse rectus abdominis
in pericardial effusion, 965 in metastatic breast cancer, 891–893 myocutaneous (TRAM) flap.
in tamponade, 962 side effects/toxicities of, 892 Transforming growth factor-β (TGFβ) signaling,
TAILORx trial, 322 Taxanes to anthracycline-based chemotherapy, 284
Tamoxifen, 272, 274f, 327, 737, 756–757, 1008 addition of, 753–754 Transforming growth factor-β (TGF-β), in bone
as adjuvant therapy for bilateral breast cancer, Taxol. See Paclitaxel. metastases, 876
971 Taxotere. See Docetaxel. Transpectoral route, of lymphatic drainage, 30f,
for advanced disease, 908 Taylor, Ian, 515 32
aromatase inhibitor and, sequential therapy with, T-DM1, for metastatic breast cancer, 898 Transverse rectus abdominis myocutaneous (TRAM)
739–741, 741t Technetium sulfur colloid, for sentinel lymph node, flap, 401f, 403f, 413f, 792–794, 793f, 795f
benign breast disease and, 225 650, 651f versus latissimus dorsi, 796t
biomarkers suggestive of benefit from, 747–748 Telomerase expression, 284 Transversus thoracis muscles, 25
for breast cancer, 221, 557 Temozolomide, for malignant gliomas, 953 Trastuzumab (Herceptin), 758–759, 765, 765t,
as breast cancer therapy, 932 Terminal duct lobular unit (TDLU), 57, 286 979
in breast conserving surgery, 704 Testicular tumors, gynecomastia and, 106–107 adjuvant trials of, 327t
clinical monitoring in, 229–230 Testosterone, for breast pain, 84 in breast cancer therapy, 928t
in CYP2D6, 230 The European Organization for Research and for cardiac dysfunction, 1052
for DCIS, 569 Treatment of Cancer 10981 to 22023 After cardiac toxicity of, 1021
effects of, in carriers of predisposing genetic Mapping of the Axilla: Radiotherapy or Surgery deescalation of therapy, 759, 759f
mutations, 229 (AMAROS), 596 duration of therapy, 758–759, 759f
endometrial hyperplasia in, 229–230 Thelarche, 44, 287–288 for locally advanced breast cancer, 824
history of, 907–908 premature, 43, 43f mechanism of action, 329
hot flashes from, 749 Therapeutic abortion, for pregnancy-associated for metastatic breast cancer, 891, 897
for long term adjuvant therapy of breast cancer, breast cancer, 998 resistance to, 897
273–274 Thiotepa, 957 monoclonal antibodies, 329
for MBC, 978 Thompson, CR., 907 Trastuzumab Beyond Progression (TBP) study,
metabolites of, 230 Thoracentesis, for pleural metastases, 936–939, 937f 897
monotherapy Thoracic cavity, lymph nodes of, 35–36 Trastuzumab emtansine (T-DMI), 766
for 5 years, 737–738, 738t, 740t Thoracic radiation therapy, risk-based screening after, Treatise on Diseases of the Breast, 8
followed by aromatase inhibitor, 742–743, 1009, 1009b Treatise on Operative Surgery, 8–9, 9f
742f, 742t Thoracic wall Treatment-related cancers, 1021–1022
for premenopausal women with invasive anatomy of, 24–26, 24f–25f Tremelimumab, 329
early-stage breast cancer, 743 lymph nodes of, 33f, 34–35 Trental (pentoxifylline), for lymphedema, 526
for 10 years, 738, 738t–739t Thoracoabdominal nerves, 25 Triad of error, for delayed diagnosis, 1064–1069,
for premenopausal women with invasive Thoracoacromial artery, 26 1065f
early-stage breast cancer, 743 Thoracodorsal nerve, 389f Trial Assigning Individualized Options for Treatment
phase II acquired resistance of, 278 Thoracodorsal neurovascular bundle, 440–441 (TAILORx), 257, 259, 747, 782
in postmenopausal women, 757 Thoracoepigastric flap, surgical technique of, Triple biopsy, in staging, 543
radiotherapy and, 674–675, 675t 483–484, 484f–485f Triple-negative breast cancer (TNBC), 319,
randomized trials of, 826, 826t 3 + 3 design, for phase I trials, 367, 367f, 367t 903–905, 904f
recommendation of, 234 3D conformal radiation therapy (CRT), 681, 681f, chemotherapy for, 325
for refractory mastalgia, 85–86 709 TRYPHANEA trial, 824
replacement of radiotherapy with, 652, 653t 3D planning, 668 Tube skin grafts, 478–479, 479f–480f
risks and benefits of, 228, 228f Three-dimensional mammography, 1069 Tube thoracostomy, 939
thromboembolism from, 749 Thrombosis, in breast cancer survivors, 1020 Tuberous breast deformity, 48–49, 48f–49f
trial, study of, 230–231 Thyroid hormone, for breast pain, 84 Tubular adenoma, 89
STAR results after 81 months of follow-up, Thyrotropin-releasing hormone, 54–55 Tubular carcinoma, 148–149, 149f
230–231 Tissue expander, surgical technique for, 481, 482f mammography of, 345, 345f
STAR trial and potential population impact, Tissue expansion/implants, 479–480 prognosis for, 255
231 Tissue necrosis, after mastectomy, 496 Tumescent technique, 414
Tamoxifen and Exemestane Trial (TEXT), 745 TLR-4 genetic polymorphism, 928–929 Tumor
Tamoxifen Exemestane Adjuvant Multinational Toker cells, in Paget disease, 169–170 assessment of, in neoadjuvant therapy, 827
(TEAM) trial, in adjuvant endocrine therapy, Tonometry, for lymphedema, 523 cells, disseminated, 320–321
740, 740f Topographic surgical anatomy, 388–391, 391f control of, surgeons responsibility for, 387
Tamoxifen-ER complex, 276 lymphatic drainage and routes for metastases in, dormancy, 320
Tangential beam arrangements, in breast, 721 390–391 heterogeneity, 321–322
Tansini, Iginio, 17, 480f neurologic innervation of pectoral muscles in, pathologic stage of, 387
Targeted axillary dissection (TAD), 786 388–390, 389f primary characteristics of, 386
Targeted axillary lymph node dissection, 601–603 vascular distribution in, 390 vascular phase of, 319–320
TARGIT-A trial, 475 Toremifene, 327, 910 Tumor, node, metastasis (TNM), 387
in DCIS, 567 for refractory mastalgia, 86 classification of breast cancer, 252t–253t
 Index 1113

Tumor, node, metastasis (TNM) system, 544 Ultrasound, 353–354, 354f–355f Value
histopathologic grade in, 548, 548t for intraductal papilloma, 67–68, 68f of care, 500
specific stages in, 545–548 intraoperative, of margins, 640–641, 641t quality and, 500
M stage as, 548, 548t of masses Van Nuys Prognostic Index (VNPI). See also
N stage (tumor size) as, 546–548, 546t–547t benign, 341–344, 344f University of Southern California/Van Nuys
T stage (tumor size) as, 545–546, 545t malignant, 354, 355f–356f Prognostic Index.
stage groupings in, 548, 548t, 549f standardized terminology for sonography for local recurrence of DCIS, 570–573
Tumor bed boost, 475 reports, 353 Variants of uncertain significance (VUS), and
Tumor biology, 691–692 in screening process, 334–335 bilateral breast cancer, 968
Tumor grade, as primary tumor characteristics, 534 Ultrasound-guided biopsy, 380–381, 380t Varicella zoster virus, 188
Tumor histology, as primary tumor characteristics, Ultrasound-guided Mammotome biopsy, for Vascular calcifications, mammography of, 348,
534 intraductal lesions, 75 349f
Tumor infiltrating lymphocytes (TILs), 286 Ultrasound-guided wire localization, 74 Vascular distribution, to breast, 390
Tumor location, as primary tumor characteristics, Uncontrolled local disease (ULD), 867 Vascular endothelial growth factor (VEGF),
533–534 Uncontrolled trials, 362, 366 283
Tumor markers. See Biological marker(s). United States, breast cancer treatment in, expression of, 899–900
Tumor microenvironment, 305 422–435 Vascular insufficiency, 489
Tumor necrosis factor-α, 284 University of Alabama Prospective Randomized Vascular neoplasms, 160–161, 192
Tumor proliferation, as primary tumor Trial, 447t Vasomotor symptoms
characteristics, 535–536 University of Medicine and Dentistry of New Jersey of menopause in breast cancer patient,
Tumor satellitosis, 171 (UMDNJ)/Yale series, 597 estrogen-based therapy for, alternatives to,
Tumor size University of Southern California/Van Nuys 1025–1027
in breast conserving surgery and radiation, Prognostic Index (USC/VNPI), for local antidepressants, 1025–1026, 1026t
695–696 recurrence of DCIS, 570–573 clonidine, 1026
as primary tumor characteristics, 532–533, 533f, University of Tokushima Prospective Trial, 448t complementary and alternative methods for,
533t Unknown primary 1026–1027
as prognostic factors, 254 axillary metastasis of, 1000–1003 gabapentinoids, 1026
in staging, 545–546 diagnosis of, 1000–1001 progesterone analogs, 1026
Tumor staging. See Staging. imaging in, 1000–1001, 1002f–1003f in women, 1018
Tumor subtyping, in breast conserving surgery and pathologic evaluation, 1001 Velpeau, Alfred-Armand-Louis-Marie, 8
radiation, 698–699 incidence of, 1000, 1001f Venalot (Coumarin), for lymphedema, 526
Tumor suppressor genes, 298–299 management of, 1001–1003 Venous drainage, of breast, 28–29, 35f, 36
DCIS and, 140–142 Upper extremity, lymph nodes of, 516–518, Venous thromboembolism (VTE), 497–498
Tumor volume, and local recurrence, 397, 397t 518f in breast cancer, 1020
Tumor-associated antigens (TAAs), 328, 924–925, Upper inner quadrants, incision for, 396, Vertebral plexus of veins, 29
925f 402f–403f Vertical mammaplasty, 581, 584f
Tumor-associated carbohydrate antigens (TACAs), Upper outer quadrants, incision for, 396, Vertical rectus abdominis myocutaneous flap
328–329 404f–405f (VRAM), 791
Tumor-infiltrating lymphocytes (TILs), 927–928 Upper quadrant dysfunction Vesalius, Andreas, 4
Turner syndrome, 50, 50f after treatment, 1033–1034 Vinca alkaloids, 952–953
12-gene recurrence score (RS), for DCIS, 141–142 biomechanics in, 1033 as cause of chemotherapy-induced peripheral
Twentieth century, history of breast cancer therapy impact on daily activities, 1034 neuropathy, 1035–1036
in, 12–18 pretreatment, 1033 for metastatic breast cancer, 895
breast reconstruction in, 17–18, 18t relationship to physical activity level, 1034, Vincristine, early trials of, 780
cancer biology in, 18 1034f Vinorelbine, for metastatic breast cancer, 888t, 890t,
chemotherapy in, 16–17 screening of, 1034, 1034b 895
hormonal therapy in, 15–16, 16f surgical intervention and, correlation of, oral preparation of, 895
mammography in, 17 1033–1034 Virginal lobule, 44
radiotherapy in, 14–15, 15f treatment of, 1034 Vital dye
surgery in, 12–14, 13t, 14f Urban, Jerome, 13 combined technique of, and radioisotope,
21-gene real-time RT-PCR assay, in staging, 539, Urokinase plasminogen activator (uPA), as biological 607
539f markers, 537–538, 537f complications of, 618–621
21-gene recurrence score, of endocrine therapy, 913 US Food and Drug Administration (FDA), on injection technique, 621, 621f
Two-dimensional versus three-dimensional conformal tamoxifen, 908 lymphatic mapping with, 618–622
versus intensity-modulated radiation therapy, US Preventive Services Task Force (USPSTF), 331, Vitamin A, for mastalgia, 87
666f, 667–669 643 Vitamin E
Type 1 insulin-dependent diabetes mellitus, lactation on breast cancer, 240 for hot flashes, 1027
and, 55 recommendations of, 233–234, 235t for mastalgia, 86–87
Typists, 512 USC/VNPI. See University of Southern California/ Vitamins, for mastalgia, 86–87
Tyrer-Cuzick model, 1006 Van Nuys Prognostic Index. VNPI (Van Nuys Prognostic Index). See also
Uterine disorders, adjuvant endocrine therapy and, University of Southern California/Van Nuys
U 749 Prognostic Index.
UK Standardisation of Breast Radiotherapy for local recurrence of DCIS, 570–573
(START) trials, 720 V Vocational rehabilitation, 1038
UK/ANZ DCIS trial, 748, 748f Vaccines, 929–930 von Volkmann, Richard, 8
Ulnar mammary syndrome, 41 Vaginal dryness von Waldeyer-Hartz, Heinrich, 8
Ulnar nerve, 27, 27f adjuvant endocrine therapy and, 749 Vulvovaginal atrophy, topical estrogens for,
Ulrich, P., 15–16 in breast cancer survivors, 1018 1027
1114 Index

W Whole-brain radiation therapy (WBRT) (Continued) X

Walpole, A.L., 907–908 toxicity of, 948 XRT (external beam radiation therapy), 669. See also
Wangensteen, Owen, 13 treatment technique and dose fractionation of, Radiation therapy.
WBRT. See Whole-brain radiation therapy. 947 standard treatment field setup of, 664–666
WECARE study, and chemotherapy, 970 Whole-heart, analysis of, 723, 723f techniques and considerations of, 664–667
Welch, William, 12 “Winged scapula,” 389f
Wellings-Jensen-Marcum model, 288–289 Wire-guided localization (WGL), of breasts, 469 Y
Westerman, C., 12 Wise pattern mammaplasty, 583, 585f Young, Samuel, 7
Whole breast irradiation, hypofractionated, patient Witch’s milk, 43 Young age, delayed diagnosis of, 1065–1066,
selection factors for, 700–701 Women, younger, delayed diagnosis of, 1067 1065f
Whole breast radiation therapy (WBRT), 663, 693, Women’s Health Initiative (WHI) Dietary Younger women, delayed diagnosis of,
694t Modification Trial, 1047, 1048t 1067
for DCIS, 567 Women’s Healthy Eating and Living (WHEL) study, ypT0 ypN0, 846
Whole-brain radiation therapy (WBRT), 1022, 1047, 1048t ypT0/is, 846
946–948 Women’s Interventional Nutrition Study (WINS), ypT0/is ypN0, 846
randomized controlled trials for, 948, 949t 1047, 1048t
and stereotactic radiosurgery boost, World Health Organization, gaps of, 501 Z
951–952 Wound, postmastectomy, care of, 492 Zoledronic acid
surgical intervention for single metastasis and, Wound care, mastectomy and, 492–498 for bone metastases, 881–882, 881t
949–950 Wound infection, after mastectomy, 493, 494f for osteoporosis, 1016–1017