Breast

BACONGA, KEZIAH
 Embryology
• 5th – 6th week of fetal development
- thickened ectoderm (mammary ridges/lines) are
evident in the embryo

3
 Embryology
• Polymastia – Presence of Acessory breast
• Polythelia – Presence of Accessory nipples
• Amastia - absence of breast. Seen in Poland’s syn
• Symmastia - webbing between the breasts

4
 Functional Anatomy 4
• Composed of 15 to 20 lobes
• Cooper’s ligament - Fibrous bands of connective
• tissue that provides structural support
• Extends from 2nd rib to 7th rib, from lateral
border of sternum to anterior axillary line
• Axillary tail of Spence – Breast tissue extends
laterally across the anterior axillary fold
Functional Anatomy 5
 Functional Anatomy 6
• Nipple-Areola Complex - pigmented and corrugated
- contains sebaceous glands, sweat glands, and
accessory glands of Montgomery
 Functional Anatomy 7
• Blood Supply:
- a) branches of internal mammary artery
- b) branches of posterior intercostal arteries
- c) branches from axillary artery
 Functional Anatomy 8
• Blood Supply:
- a) branches of internal mammary artery
- b) branches of posterior intercostal arteries
- c) branches from axillary artery
 Functional Anatomy 9
• Veins - follow the course of the arteries
-three principal groups
-a) branches of internal thoracic vein,
-b) branches of posterior intercostal veins
-(c) tributaries of the axillary vein
-Batson’s vertebral venous plexus - provides
route for breast cancer metastases to the
vertebrae, skull, pelvic bones, and central
nervous system.
Functional Anatomy 10
 Functional Anatomy 11
• Nerve Innervation
-3rd – 6th intercostal nerves - provide sensory
innervation of breast & anterolateral chest wall.
-Supraclavicular nerve - skin upper portion of
breast
-Intercostobrachial nerve - sensation over the
medial aspect of the upper arm.
Functional Anatomy 12
 Functional Anatomy
• Six axillary lymph node groups
a) Axillary vein group (lateral)
- receive most of drainage from upper ext
b) External mammary group (anterior/pectoral)
- receive most of drainage from lateral
aspect of the breast
c) Scapular group (Posterior/subscapular)
- receive drainage from lower posterior
neck, posterior trunk, & posterior
shoulder 14
 Functional Anatomy 14
• Six axillary lymph node groups
d) Central group
- receive drainage from axillary vein,
external mammary, and scapular groups
e) Subclavicular group (apical)
- receive drainage from all other groups of
axillary lymph nodes
f) Interpectoral group (Rotter’s lymph nodes)
- receive drainage directly from breast.
Functional Anatomy 15
 Functional Anatomy 16
• Lymph node levels according to anatomic
relationship with pectoralis minor:
- Level I - lateral to the lateral
border of pectoralis minor
muscle
- axillary vein, external mammary, and
scapular groups
- Level II - superficial or deep to
pectoralis minor muscle
- central and interpectoral groups
 Functional Anatomy 17
• Lymph node levels according to anatomic
relationship with pectoralis minor:
- Level III - medial to medial border of pectoralis
minor muscle.
- subclavicular group.

• Axillary lymph nodes usually receive >75% of the

lymph drainage from the breast
 Physiology of the Breast 18
• Estrogen - initiates ductal development,
• Progesterone - for differentiation of epithelium and
for lobular development
• Prolactin - for lactogenesis in late pregnancy and the
postpartum period
• Oxytocin – for milk letdown
EXAMINATION OF THE
BREAST
General Guidelines

 Male examiners should normally be

chaperoned
 Texture: smooth to granular
 menstrual cycle and during pregnancy
 Nodularity and tenderness often increase towards
the end of the cycle and during menstruation

 Asymmetrical so always examine

both and compare one to the
other
The patient should be undressed
to the waist and seated with arms
by side
 Breast  Nipples
 size  everted, flat,
 symmetry or inverted
(note if recent
 shape of change or
breast longstanding
 skin colour  cracking or
 superficial ‘eczema’
veins  bleeding or
discharge
Nodules

 Location (by quadrant or clock)

 Size in cm
 Shape
 Consistency
 Delimitation
 Tenderness
 Mobility
Nipple

 Discharge
 Milky (hypothyroidism, prolactinoma, drugs)
 Bloody (papilloma, Paget’s disease)
AXILLARY

 The patient’s forearm is rested across the

examiner’s forearm
 An alternative is to ask the patient to rest
their hand on the examiner’s shoulder
 The examiner feels for each group of nodes,
while steadying the shoulder with the other
hand
 apical
 anterior (posterior surface of anterior axillary fold)
 medial (on the chest wall)
 lateral (against the humerus)
 posterior (anterior surface of posterior axillary fold)
Relative risk of Breast Ca

 Personal history of breast abnormalities.

 Two breast tissue abnormalities—ductal
carcinoma in situ (DCIS) lobular carcinoma in
situ (LCIS)—are associated with increased risk for
developing invasive breast cancer.

 Age
 The risk of developing breast cancer increases
with age
 The majority of breast cancer cases occur in
women older than age 50.
Relative risk of Breast Ca

 Age at menarche (first menstrual

period). Women who had their first
menstrual period before age 12
have a slightly increased risk of
breast cancer.

 Age at first live birth. Risk depends

on age at first live birth and family
history of breast cancer
Relative risk of Breast Ca

 Breast cancer among first-degree

relatives (sisters, mother, daughters)

 Breast biopsies
 atypical hyperplasia

 Race
 White women have greater risk of
developing breast cancer than Black
women (although Black women
diagnosed with breast cancer are more
likely to die of the disease).
Routine Mammogram

American Cancer Society

 Patients 20-40 years old – every 3 years
 Patients>40 - every year
Triple Negative Rule

 benign-feeling lump
 negative mammogram
 negative fine-needle aspiration
 Benign Breast Diseases 43
• Cysts – fluid filled masses
- Needle biopsy - allows for the early diagnosis
and treatment of cysts preferably ultrasound-
guided to note any mass.
- cytologic examination of such fluid is
NOT cost effective unless blood-stained
 Benign Breast Diseases 44
• Fibroadenoma - aged 15 to 25 years
- grow to 1 or 3 cm in diameter then stable
- risk of breast cancer is very low
- Dx: hard, movable, non-tender, well delineated
- Ultrasonography
- Tx: Observation
Cryoablation
Ultrasound-guided vacuum assisted biopsy
Excision biopsy - >3cms
 Benign Breast Diseases 45
• Fibrocystic change - Cyclical mastalgia & nodularity
- associated w/ premenstrual enlargement of
breast and are regarded as normal
 Risk Factor for Breast Cancer
• Risk Assessment Models
- Gail model - most frequently used in US
- includes the ff:
- age
- age at menarche
- age at first live birth,
- number of breast biopsy specimens
- history of atypical hyperplasia
- number of first-degree relatives w/ breast
34
Cancer
 Risk Factor for Breast Cancer
• Risk Assessment Models
- Claus model - incorporates more information about
family history but excludes other risk factors
- BRCAPRO model - Mendelian model calculates
the probability that an individual is a carrier of a
mutation in one of breast cancer susceptibility
genes based on their family history of breast and
ovarian cancer
- Tyrer-Cuzick model - utilize both family history
information and individual risk information 35
 Risk Factor for Breast Cancer
•Risk Management
•when to use postmenopausal hormone replacement
Therapy
• At what age to begin mammography screening or
incorporate magnetic resonance imaging (MRI)
screening
•When to use tamoxifen to prevent breast cancer
• when to perform prophylactic mastectomy to
prevent breast cancer
36
 49

Diagnostics
 Physical Exam
50

2/25/2018
Masses: shape
 Masses: margins

Circumscribed Obscured Microlobulated Ill defined Spiculated

 Sonography
• Choice for patients with dense breast
• Differentiate solid from cystic lesions
• Does not visualize calcification
• Lymph node involved with cancer
- cortical thickening
- change in shape to more circular appearance
- size larger than 10 mm
- absence of a fatty hilum & hypoechoic internal
echoes.
41
Sonography Findings of Breast Cancer

1. hypoechoic, poorly defined, irregular mass

2/25/2018 42
Sonography Findings of Breast Cancer55

2. hypoechoic mass with microlobulation or fine

irregularities of the margins

2/25/2018
Sonography Findings of Breast Cancer56

3. spread vertically (taller than wide)

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 57
Mammographic Findings of Breast Cancer

1. irregular border or a star-burst appearance

(spiculated)

2/25/2018
Mammographic Findings of Breast Cancer

2. Microcalcifications

 Concentrated in 2 x 2 cm area; linear and branching

2/25/2018 46
 Diagnostics 59

•Mammography

Magnification View
 Mammography
60
• Screening modality of choice for patients more than
40 years old
• Visualizes calcifications, lymph nodes, fibrous
tissue pattern.
• MLO view - images the greatest volume of breast
tissue, including the upper outer quadrant and the
axillary tail of Spence
• CC view - better visualization of the medial aspect
of the breast and permits greater breast compression
Mammographic findings that mandate
immediate breast biopsy
1. Masses that increase in size.
2. Circumscribed & dense masses w/ indistinct
margins.
3. > 5 microcalcifications w/in 1 square centimeter.
4. Masses that recur after 3 cyst aspiration.
5. Architectural distortion compared to the
contralateral breast.
6. Spiculated mass associated w/ microcalcifications.
 Diagnostics 62
•Mammography findings of breast cancer
compared to fibroadenoma
 Diagnostics 63
•Mammography findings of breast cancer
 Diagnostics
•Mammography findings of breast cancer

Spiculated primary tumor 52

 Diagnostics
•Mammography findings of breast cancer

Architectural Distortion 53
71
 Mammography
67
• Ductography - Indication is bloody nipple discharge
- Radiopaque contrast media is injected into one
or more of the major ducts and mammography
is performed.
- Mammography obtained without compression.
- Intraductal papillomas - small filling defects
surrounded by contrast media
- Cancers - irregular masses or multiple
intraluminal filling defects
 Magnetic Resonance 68
Imaging
1. Defining local extent of invasive cancer
2. Identification of occult breast cancer ((+) LN, (-)
mammogram)
3. Distinguishing scar from recurrent tumor
4. Staging breast cancer
5. Monitoring response to neoadjuvant chemotherapy
6. Detection of cancer in patients with implant
7. Screening high risk women (?)

Smith J, Breast Cancer Research and Treatment, 2003

 MRI
• With negative findings on both mammography and
physical examination, breast cancer being diagnosed
by MRI is extremely low.
• Useful in the following:
- evaluation of px presenting w/ nodal metastasis
w/o identifiable primary tumor
- assess response to therapy in neoadjuvant
- in selecting px for partial breast irradiation
- evaluation of treated breast for tumor
recurrence. 74
Magnetic
Resonance 70
Imaging
Mammographic Needle 71
Localization Biopsy
• For non-palpable suspicious tumors by imaging
• Tip of Needle is placed at the center of the mass
with the help of Mammography
• Wide excision is done and specimen is sent for x-ray
• Under general anesthesia or sedation
Mammographic Needle 72
Localization Biopsy
Procedure
• Patient brought to the mammography unit
78
79
Mammographic Needle
Localization Biopsy
Procedure
• Patient brought to the operating room

80
81
82
Mammographic Needle
Localization Biopsy
Procedure
• Postlumpectomy mammography

83
84
……
Mammotome® Vacuum Biopsy System81

2/25/2018
 Mammotome® Vacuum Biopsy System82

• Allow multiple incision biopsy under imaging

until all mass is excised

2/25/2018
 Encor® Breast Biopsy System

2/25/2018 88
Preoperative Diagnostic Work-ups

Fine Needle Aspiration

Biopsy

Core Needle (g. 14-18)

Aspiration Biopsy

Incision Biopsy
 Biopsy 85
• Fine Needle Aspiration Cytology
- Uses G23 needle in a 10cc syringe
- advantage: easy and cheap
- disadvantage: dependent on cytologist
- does not show tissue invasion
 Biopsy 86
• Core Needle Biopsy
- Uses G14 needle
- advantage:
- show tissue invasion
- tissue used for hormonal receptor assay
- needle is affordable
- low complication rate
- minimal scarring
 Biopsy 87
• Incision Biopsy
- Biopsy under local anesthesia
- Used for large breast masses (>/= 4cm)
- advantage: can show tissue invasion
- disadvantage: non-therapeutic but can be
done under frozen section for definitive
surgery
 Biopsy 88
• Excision Biopsy
- Biopsy under local anesthesia
- Used for small breast masses (< 4cm)
- advantage: can show tissue invasion
- disadvantage: therapeutic for benign masses
- can be done under frozen section for
definitive surgery
 Sentinel Lymph Node Biopsy
• Used Breast Cancer with non-palpable lymph node
for axillary staging
• Advantage: less occurrence of Lymphedema
• Uses radioisotope and/or Methylene blue
• Intradermal better than intraparenchymal
injection but causes tattooing.
• One day preoperatively vs. same day radioisotope
injection = same
Lymphoscintigram and Mammogram
2/25/2018 97
Lymphoscintigram
The Gamma probe
2/25/2018 100
Injecting Isosulfan blue dye
subareolar
Left breast mass

102
2/25/2018 103
104
 Histopathology of Breast Cancer
• Multicentricity - occurrence of a second breast
cancer outside the breast quadrant of the primary
cancer (or at least 4 cm away)
• Multifocality - occurrence of a second cancer within
the same breast quadrant as the primary
• In situ breast cancer - absence of invasion of cells
into the surrounding stroma
- confined within natural ductal and alveolar
boundaries
105
 Lobular Carcinoma in Situ

-noninvasive proliferation of cells

arising from the breast lobules and
terminal ductal area
-typically discovered as an incidental
pathologic finding on biopsy
performed for another indication

- Multicentricity – 60 – 90%
- 50 – 70% bilateral

Lobular Carcinoma in Situ 106

 Lobular Carcinoma in Situ
• A marker for increased risk rather than an inevitable
precursor of invasive disease
• Tx options: observation
- chemoprevention
- bilateral total mastectomy
** goal is to prevent or detect at an early stage.

101
 Lobular Carcinoma in Situ
• Tx options: observation
** No benefit to excising
- diffusely involves both breasts
- Tamoxifen as a risk reduction strategy

102
 Ductal Carcinoma in Situ

Non-invasive neoplasm of ductal origin

that can progress to invasive cancer in
some cases
 40 – 80% multicentricity
 10 -20% bilateral
80% - diagnosed by mammography
Treatment:
- excision
- excision + radiation
- mastectomy
Ductal Carcinoma in Situ - breast conserving surgery 109
Invasive Lobular Carcinoma Invasive Ductal Carcinom1a10
Histopathology of Breast Cancer

105
Histopathology of Breast Cancer
• Classification of breast ductal carcinoma in situ (DCIS)

Determining Characteristics
• Histologic Subtype Nuclear Grade Necrosis DCIS Grade
• Comedo High Extensive High
• Intermediate Intermediate Focal/absent Intermediate
• Noncomedo Low Absent Low

106
Histopathology of Breast
Cancer

107
 Invasive Breast Carcinoma
• Paget’s disease - chronic, eczematous eruption of
the nipple, may progress to an ulcerated lesion
- usually is associated with DCIS & with
invasive cancer
- Dx: Nipple biopsy - cells that are identical to
the underlying DCIS cells (pagetoid features)
- Pathognomonic: (+) large, pale, vacuolated
cells (Paget cells) in the rete pegs of epith.

108
Invasive Breast Carcinoma

109
 Invasive Breast Carcinoma
• Paget’s disease VS Pagetoid intraepithelial
melanoma
-(+) S-100 antigen immunostaining in melanoma
-(+) CEA immunostaining in Paget’s disease.
- Tx: lumpectomy or mastectomy
- depend on
1) involvement of nipple-areolar complex
2) (+) DCIS or invasive cancer

110
 Invasive Breast Carcinoma
• Invasive ductal carcinoma w/ productive fibrosis
- (scirrhous, simplex, NST)
- 80% of breast cancers
- 5th – 6th decades of life as a solitary, firm mass.
-shows estrogen receptor expression

111
Invasive Breast Carcinoma

118
 Invasive Breast Carcinoma
• Medullary carcinoma - 4% of invasive breast Ca
- frequent phenotype of BRCA1 (+) breast cancer.
- Grossly, the cancer is soft and hemorrhagic
- Bilaterality in 20% of cases
- microscopically:
- a) dense lymphoreticular infiltrate
- b) large pleomorphic nuclei that are
poorly differentiated and show active
mitosis
- c) sheet-like growth pattern w/ minimal
 Invasive Breast Carcinoma
• Medullary carcinoma
- 50% associated with DCIS
- <10% demonstrate hormone receptors
- benign or hyperplastic lymphadenopathy of
axilla contribute to erroneous clinical staging
- better 5-year survival rate than NST or invasive
lobular carcinoma.

114
 Invasive Breast Carcinoma
• Mucinous carcinoma (colloid carcinoma)
- 2% of all invasive breast cancers
- defined by extracellular pools of mucin
- 90% of mucinous carcinomas display hormone
receptors
- 5- & 10-year survival rates are 73% and 59%,
respectively

115
 Invasive Breast Carcinoma
• Papillary carcinoma - 2% of all invasive breast Ca
- small and rarely attain a size of 3 cm
- defined by papillae with fibrovascular stalks
and multilayered epithelium
- 87% express estrogen receptor
- Low frequency of lymph node metastases
- 5- and 10-year survival rates similar to those
for mucinous and tubular carcinoma.

116
 Invasive Breast Carcinoma
• Tubular carcinoma - 2% of all invasive breast Ca
- a haphazard array of small, randomly arranged
tubular elements is seen
. - 94% express estrogen receptor
- 10% develop axillary lymph node metastases
- metastatic in one or two axillary lymph
nodes does not adversely affect survival
- Distant metastases are rare in tubular Ca &
invasive cribriform Ca
- Long-term survival approaches 100%. 123
 Invasive Breast Carcinoma
• Invasive lobular carcinoma - 10% of breast Ca
- intracytoplasmic mucin, displace the nucleus
(signet-ring cell carcinoma)
- frequently multifocal, multicentric, & bilateral.
- insidious growth pattern
- 90% express estrogen receptor

118
 Breast Cancer Staging
• Determined by PE of skin, breast tissue, and
regional lymph nodes
• PE of axillary LN mets accuracy of only 33%.
• Ultrasound (US) is more sensitive than physical
examination alone LN assessment
• TNM (tumor, nodes, and metastasis) system.
• Routine biopsy of internal mammary lymph nodes is
not generally performed

119
Breast Cancer Staging

126
Breast Cancer Staging

127
 Biomarkers
• a) the steroid hormone receptor pathway: ER/PR
• b) growth factors and growth factor receptors:
(HER-2)/neu, EGFR, transforming growth factor,
PDGF, & insulin-like growth factor family
• c) indices of proliferation: proliferating cell nuclear
antigen (PCNA) and Ki-67
• d) indices of angiogenesis: vascular endothelial
growth factor (VEGF) & angiogenesis index
• e) mammalian target of rapamycin (mTOR)
signaling pathway 128
 Biomarkers
• f) tumor-suppressor genes: p53
• g) cell cycle, cyclins, & cyclin-dependent kinases
• h) proteasome
• i) COX-2 enzyme
• j) peroxisome proliferator-activated receptors
(PPARs)
• k) indices of apoptosis & apoptosis modulators such
as bcl-2 and the bax:bcl-2 ratio.

129
 BREAST CANCER THERAPY
• 1) Diagnosis of breast cancer by biopsy
• 2) Staging of Disease
• 3) Therapeutic options offered based on Stage,
biologic subtype and general health status

139
125
126
127
128
129
130
131
Breast Conserving
Surgery (BCS)

-Lumpectomy
-Axillary Dissectiion
-Radiation therapy to the
breast

132
BREAST-CONSERVING SURGERY

Removal of the bulk of the tumor

Delivery of moderate doses of
radiation
Preservation of a good cosmetic
appearance of the breast

133
 Absolute Contraindications for
BCS with Radiation
Women with two or more primary tumors in
separate quadrants; diffuse malignant-appearing
microcalcifications.
History of previous irradiation to the breast region.
Pregnancy
Persistent positive margins after reasonable surgical
attempts.

140
 Relative Contraindications for
BCS with Radiation
History of collagen vascular disease.
Patients with multiple gross tumors in the
same quadrant and indeterminate
calcifications.
Tumors larger than 4-5 cm; large tumor in a
small breast.
Large or pendulous breasts (technical
difficulty to obtain adequate radiation dose
homogeneity).
135
136
 Adjuvant chemotherapy
• Early-stage invasive breast cancer
1) node-positive cancers
2) patients with cancers >1 cm
3) node-negative cancers of >0.5 cm when
adverse prognostic features are present.

137
 Adjuvant chemotherapy
• Adverse prognostic factors
- blood vessel or lymph vessel invasion
- high nuclear grade
- high histologic grade
- HER-2/neu overexpression or amplification
- negative hormone receptor status.

138
 Adjuvant chemotherapy
• Doxorubicin
• Cyclophosphamide
• Paclitaxel

139
 Adjuvant Endocrine Therapy
• for women with hormone receptor-positive cancers
• Tamoxifen for premenopausal
• Aromatase inhibitor is recommended if the patient is
postmenopausal.
• Trastuzumab for HER-2/neu receptor positive
• doxorubicin, cyclophosphamide, and paclitaxel

• Oophorectomy was used in premenopausal breast

cancer patients
140
 NeoAdjuvant Therapy
• considered in the initial management of patients
with locally advanced stage III breast cancer.
• 2 cycles of Chemotherapy followed by
• Modified radical mastectomy followed by adjuvant
radiation therapy

141
 Radiation Therapy
• For stages IIIA and IIIB breast cancer are
a) to breast & supraclavicular lymph nodes after
neoadjuvant chemotherapy & segmental
mastectomy w/ or w/o ALND
b) to chest wall & supraclavicular lymph nodes after
neoadjuvant chemotherapy & mastectomy w/ or
w/o ALND
c) to chest wall & supraclavicular lymph nodes after
segmental mastectomy or mastectomy w/ ALND
148
and adjuvant chemotherapy
Linear Accelerator Cobalt Therapy

149
 Breast Reconstruction

Trans–rectus Abdominis Muscle (TRAM) Reconstruction

150
Breast Reconstruction

152
153
Breast Reconstruction
Lattisimus Dorsi Flap

154
 Breast Cancer during pregnancy
• MRM can be performed during 1st & 2nd trimesters
• 3rd trimester – lumpectomy w/ ALND can be
considered, radiation deferred until after delivery.
• Chemotherapy at 1st trimester - risk of spontaneous
abortion and a 12% risk of birth defects
• No evidence of teratogenicity of chemotherapy –
- 2nd & 3rd trimesters

149
Metastatic Breast Cancer
• Treatment options:

- chemotherapy
- radiation therapy
- Tumor debulking/ Toilet mastectomy
- improvement of quality of life

160
 161
Frequency of breast cancer metastas e s
Pulmonary Metastasis with
Pleural Effusion
• Thoracentesis

152
Pulmonary Metastasis
• Tube Thoracostomy

153