Volume 69, Number 5

OBSTETRICAL AND GYNECOLOGICAL SURVEY

Copyright © 2014
by Lippincott Williams & Wilkins CME REVIEW ARTICLE
CHIEF EDITOR’S NOTE: This article is part of a series of continuing education activities in this Journal through which a
13
total of 36 AMA PRA Category 1 Credits™ can be earned in 2014. Instructions for how CME credits can be earned
appear on the last page of the Table of Contents.

Cancer and Pregnancy: The Clinician’s

Perspective
Sarah Dotters-Katz, MD,* Michael McNeil, BA,† Jane Limmer, MD,‡
and Jeffrey Kuller, MD§
*Resident, Obstetrics and Gynecology, and †Medical Student, Department of Obstetrics and Gynecology, Duke University
Medical Center, Durham, NC; {Instructor of Obstetrics and Gynecology, University of Colorado Hospital, Denver, Colorado; and
§Professor of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Duke University Medical Center, Durham, NC

Although uncommon, the incidence of cancer complicating pregnancy is increasing. Managing

these pregnancies creates many diagnostic, therapeutic, and ethical dilemmas for the patient, her
family, and the medical care team. Despite concerns for fetal well-being, maternal survival should be
the first priority. Although surgery and chemotherapy may be used during pregnancy, radiation is gen-
erally contraindicated. For most nongynecologic cancers, termination of pregnancy does not improve
maternal outcome. Iatrogenic prematurity is the most common pregnancy complication associated
with malignancy in pregnancy because many of these infants are delivered early to facilitate maternal
treatment. Overall, maternal cancer survival is generally good and does not differ from that of nonpreg-
nant patients.
Target Audience: Obstetricians and gynecologists, hematologists/oncologists, family physicians, nurse
midwives
Learning Objectives: After completing this CME activity, physicians should be better able to describe
differences in diagnostic imaging when treating pregnant patients with malignancy; explain basic principles
of surgery, chemotherapy, and radiation therapy during pregnancy; identify cancers known to metastasize
to the placenta and to the fetus; and choose the appropriate diagnostic and treatment considerations for
pregnant women with certain nongynecologic malignancies.

General Aspects of Cancer and Pregnancy approximately 1 in 1000 to 1500 pregnancies, the in-
cidence is rising.1–3 Multiple authors have reviewed
When a pregnant woman is diagnosed with cancer, various aspects of this topic during the last few years,
multiple challenging questions arise. Whereas the highlighting its importance.4–6 The purpose of this
woman’s first question may be “what does this mean review was to familiarize obstetric providers with
for my baby?” the clinician’s first concern must be common diagnostic and therapeutic dilemmas that
for the health and survival of the woman. The overlap arise when cancer is identified during pregnancy. This
of cancer and pregnancy poses many difficult diag- review should also allow obstetricians to feel more
nostic, therapeutic, and pregnancy-related challenges comfortable consulting with hematologist/oncologists
for the obstetrician as well as for the patient and or other members of the care team who are less com-
her family. Although malignancy complicates only fortable treating women who are pregnant. After
discussing the diagnostic and treatment modalities as
All authors and staff in a position to control the content of this CME these relate to malignancy during pregnancy, this re-
activity and their spouses/life partners (if any) have disclosed that view will then focus on presentation, evaluation, treat-
they have no financial relationships with, or financial interests in,
ment, and pregnancy implications for commonly seen
any commercial organizations pertaining to this educational activity.
Correspondence requests to: Sarah Dotters-Katz, MD, 2406 nongynecologic cancers.
Blue Ridge Rd, Suite 200, Raleigh, NC 27607. E-mail: sarah. Because every woman, partner, and family will ap-
[email protected]. proach the diagnosis with different values and beliefs,
www.obgynsurvey.com | 277

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278 Obstetrical and Gynecological Survey

it is important to include the patient as part of the in the second trimester, avoiding organogenesis in
decision-making process. To provide the best care the first trimester and concerns of caval compression
to the patient, a multidisciplinary care team is essen- in the third trimester.15 When maternal survival is not
tial. Cancer identification may also be challenging affected by postponing surgery until after delivery,
because many symptoms of malignancy, including such as in the case of some thyroid cancers, surgery
nausea, anemia, and fatigue, are also common and should generally be deferred.16,17 Regional anesthe-
normal in pregnancy. Thus, when a woman presents sia is preferred over general anesthesia if possible,
with symptoms such as these that seem out of propor- although general anesthesia is not thought to be ter-
tion to her gestational age, malignancy should be con- atogenic.18–20 Before 24 weeks, documentation of fe-
sidered. Another crucial factor in the management of tal heart tones before and after surgery should be
this patient is the gestational age at diagnosis. Cancers performed; after 24 weeks, intraoperative monitoring
diagnosed in the first trimester often create the most should be considered when feasible.6 However, it is
challenges. When it does not affect outcomes, sur- important to note that, on the basis of location of op-
gery and chemotherapy should be postponed until erative field, continuous intraoperative monitoring
the second trimester. Generally, pregnancy termina- may not be possible. When this is the case, the obstet-
tion does not improve maternal outcome. However, ric provider and the surgeon should use clinical judg-
there are some aggressive tumors for which postpon- ment as to if, when, and how frequently heart tones
ing therapy even a few weeks can prove deadly. In should be assessed. If changes in fetal heart tones are
these cases, immediate treatment with or without ter- noted intraoperatively, maternal positioning in the left
mination is imperative. lateral tilt, optimizing maternal oxygenation, and en-
suring adequate blood pressure may help improve fetal
Diagnostic Tools and Pregnancy status. When these interventions do not improve fetal
status, clinical judgment must prevail in each specific
During pregnancy, workup and staging procedures
situation as to whether delivery is indicated.
are often modified to minimize radiation exposure.
Chemotherapeutic agents are often necessary dur-
Radiographs should be minimized and, when neces-
ing pregnancy, despite the potential teratogenic risks.
sary, should be accompanied by fetal shielding. Ra-
Most chemotherapeutic medications are pregnancy
diation exposure limits vary between sources, but
category D. Details about cancer-specific chemo-
generally, less than 5 rad of cumulative dose is con-
therapies are beyond the scope of this review. How-
sidered safe.6,7 Ultrasound is safe in all trimesters
ever, general risks and concepts will be discussed.
and is useful to evaluate the liver and the kidneys.
The risks of chemotherapy to the fetus are highest
Computed tomography (CT) should be avoided when
during organogenesis. Thus, if delaying treatment is
possible because of the fact that it typically involves
not thought to affect maternal survival, it should be
significant radiation exposure. When necessary, CT
deferred until after the first trimester.21–23 Growth re-
should be done without contrast.8,9 Magnetic reso-
striction, spontaneous abortion, and intrauterine fetal
nance imaging (MRI) is thought to be safe after the
demise may be seen when chemotherapy is used in
first trimester.10 The effects of gadolinium on the fe-
the second and the third trimester.21,22,24 Serial
tus are poorly studied, and thus, its use should be
growth ultrasounds should be considered for women
avoided. Positron emission tomography scan and bone
with malignancy during pregnancy, independent of
scans are high in radiation exposure but may be neces-
when or if chemotherapy is initiated.6 Ideally, che-
sary. If performed in pregnancy, these studies should
motherapy should be stopped 2 to 3 weeks before de-
be performed with proper shielding, ample maternal
livery, or at approximately 35 weeks, to allow for the
hydration, and a lower dose of radioactive tracer.11
recovery of the fetal and maternal bone marrow, thus
minimizing the risk for infection and sepsis in both
Treatment of Malignancy: Surgery,
the mother and the baby.2,25 Multiple studies have
Chemotherapy, and Radiation Therapy
failed to identify long-term neurologic or develop-
Although the management of malignancy in preg- mental sequelae in children who were exposed to
nancy is usually similar to management outside preg- chemotherapy in utero.26–28 However, more data are
nancy, there are some gestation-specific considerations. needed to confirm the safety of various regimens. It
Anticoagulation should be strongly considered given is important to note that many of the medications used
the increased risk for venous thromboembolism as- to treat the side effects of chemotherapy, including
sociated with both malignancy and pregnancy.12–14 ondansetron (pregnancy category B), metoclopra-
If surgery is indicated, it should ideally be performed mide (pregnancy category B), corticosteroids, and

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 Cancer and Pregnancy • CME Review Article 279

granulocyte colony-stimulating factors (pregnancy diagnosed during pregnancy.72,73 Stage at diagnosis

category C), are generally safe in pregnancy.29 is not affected by pregnancy, despite many symptoms
Radiation therapy (RT) is usually avoided in preg- of pregnancy being similar to those of acute leuke-
nancy. Shielding can be used, but scatter still occurs. mia.74 Leukemia is diagnosed by bone marrow biopsy.
The effects of scatter on the fetus vary based on the size Because of the aggressive nature of these cancers, treat-
and location of the radiated field and the source of ra- ment should be initiated upon diagnosis, regardless of
diation used.8 Anomalies, growth restriction, and fetal trimester. Because of this, termination should be con-
demise have all been associated with higher amounts sidered when leukemia is diagnosed in the first trimes-
of radiation exposure in utero.30 An increased risk for ter. Acute myeloid leukemia is treated with cytarabine
childhood cancers and delayed neurodevelopmental and anthracycline.39,75,76 Acute lymphoid leukemia,
outcomes have been seen in children exposed to lower the more aggressive of the 2 cancers, is treated with a
doses of radiation in utero.31,32 Despite these risks, combination of cytarabine, cyclophosphamide, Vinca-
there may be times when maternal well-being is com- alkaloids, L-asparaginase, anthracyclines, and steroids.77
promised, or the tumor is located remote from the ab- Disease course and survival are not altered in preg-
domen, and thus, radiation may be indicated.15,33–36 nant women compared with nonpregnant women.78–80
However, pregnancy is adversely affected by leuke-
Delivery Considerations mia. Increased rates of preterm delivery, growth re-
The timing of delivery in patients with known malig- striction, intrauterine fetal demise, and spontaneous
nancy poses another challenge. If the disease is stable, abortion have been noted in this population.73,80,81
delivery at term (37 weeks) is usually possible. How- The hematologic changes seen with acute leukemia
ever, if early delivery is indicated for maternal in- may compound the physiologic changes of pregnancy,
dications, corticosteroids for fetal lung development leading to increased risk for thrombosis, placental
are recommended. Cesarean delivery may be needed congestion, and disseminated intravascular coagula-
in cases of lytic pelvic lesions, in cases of obstructing tion.5,81 These complications can be minimized by
tumors (either vaginally or within the pelvis), or to maintaining hemoglobin greater than 9.8 mg/dL, main-
augment dual surgical procedures.8,10,20,36,37 If none taining platelets greater than 30,000/ mL, and using
of these issues are present, cesarean delivery may be leukophoresis in the setting of extreme leukocytosis. Pro-
reserved for obstetric indications. Multiple cancers phylactic anticoagulation should be considered.74,82,83
are known to metastasize to the placenta, including In contrast to the leukemias, Hodgkin lymphoma
most commonly melanoma, leukemia, and lymphoma. usually presents with painless lymphadenopathy.
However, placental metastasis from gastric cancer, Workup should involve chest x-ray and MRI of the
lung cancer, sarcomas, liver cancer, pancreatic cancer, chest, the abdomen, and the pelvis, but definitive di-
adrenal cancer, and cervical cancer has also been agnosis requires lymph node biopsy.74 Survival rates
reported.12,13,16–22,38–40 The placenta in any patient and stage at diagnosis are not adversely affected by
with known malignancy should be sent for pathologic pregnancy, and termination does not improve out-
evaluation.38 Metastatic disease to the fetus is incredi- comes.74,84,85 Treatment regimens vary by stage of
bly rare and has been documented only in melanoma, disease. Unlike other hematologic malignancies,
leukemia, and lymphoma.38,41,42 treatment can often be postponed until the second tri-
mester if diagnosed early in pregnancy or until after
Malignancies in Pregnancy delivery if diagnosed in the third trimester, without
affecting outcomes.86–88 Many patients can be treated
Melanoma, breast cancer, thyroid cancer, colon with single-agent therapy (vinblastine or anthracy-
cancer, and the hematologic malignancies are the clines).86–88 However, in higher-stage disease or when
most common cancers encountered in pregnancy.43,44 patients progress on single-agent therapy, doxorubi-
These are each reviewed below. Other less common cin, vincristine, bleomycin, and dacarbazine (ABVD)
malignancies are reviewed in Table 1. is used.81,89 In the setting of well-controlled disease,
delivery is recommended at ~37 weeks. Other hema-
Hematologic Malignancies
tologic malignancies are described in Table 2.
Hematologic malignancies, including, leukemias,
lymphomas, and multiple myeloma, account for 1 of
Breast Cancer
4 cancers diagnosed in pregnancy.43 Acute leuke-
mias, including acute myeloid leukemia72 and acute Gestational breast cancer—defined as breast cancer
lymphoid leukemia, comprise 90% of all leukemias diagnosed during pregnancy and the first postpartum

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280 Obstetrical and Gynecological Survey

TABLE 1
Other Malignancies and Pregnancy
Malignancy Diagnosis in Pregnancy Treatment in Pregnancy Delivery Implications Other Considerations
Sarcomas* Distant site: x-ray with Surgery as needed37 Preterm delivery as needed No difference in stage at
pelvic shielding to expedite maternal diagnosis, disease
treatment20,46 progression, or
outcomes20,46–48
US or MRI if lesion is in Defer radiation until after Consider cesarean delivery Tumors in/near pelvis may
the pelvis, the hips, or delivery20,36,37,45,46 for obstructing tumors or lead to preterm labor
the upper and lower questions of osseous or growth restriction36
extremity integrity10,11,76
Biopsies are safe Chemotherapy in second/
third trimester
Regional chemotherapy
also effective36
Glioma, CT/MRI both Systemic steroids safe Consider passive second Tumors often increase in
glioblastoma, effective10,49,50 for symptom control stage to avoid increases size in pregnancy
and in intracranial because of fluid
meningioma pressure54,55 retention and vascular
engorgement8,53,57
Levetiracetam† and Cesarean delivery with Steroid receptors on
lamotrigine† are safe51 general anesthesia to tumors also lead to
avoid risks of neuroaxial tumor growth58–61
blocks
also reasonable54,55
Increase in symptoms → Delivery timing dependent
consider surgery or on patient stability10,54–56
radiation8,52
Acute maternal
deterioration should
prompt craniotomy
with delivery if fetus
is viable15,53,54
Lung cancer MRI of the chest effective Chemotherapy as soon Preterm delivery as needed Fetal and placental
as possible after to expedite maternal metastasis noted62,63
diagnosis62,63 treatment
Biopsy of a lymph node Insufficient data to use No evidence that Commonly diagnosed in
safe; bronchoscopy safe targeted agents62 termination improves second/third
62
in experienced hands survival65 trimesters66
Postpartum surgery and No difference in tumor
radiotherapy64 behavior during
pregnancy67
Gastric cancer Endoscopy safe in Immediate resection if Preterm delivery often Survival unaffected by
pregnancy68,69 diagnosed < 25 weeks71 needed to expedite pregnancy70
maternal operative
management70,71
Tumor markers not Delivery then resection for Incidence not increased
helpful70 diagnosis > 30 weeks71 in pregnancy70
*Includes osteosarcoma, chondrosarcoma, and Ewing sarcoma.
†Both lamictal and lamotrigine are pregnancy category C.
US, ultrasound.

year—occurs in 15 to 35 per 100,000 pregnan- higher stage, more poorly differentiated, and less
cies.43,44,96–98 The incidence is increasing as more commonly estrogen- or progesterone-receptor posi-
women delay childbearing.99–101 Histologically, the tive.98,102–104 A family history of breast cancer or a
most common type of gestational breast cancer is in- personal history of BRCA1 or BRCA2 mutation are
filtrating ductal adenocarcinoma, just as it is the most strong risk factors of developing gestational breast
common in nongestational breast cancer. However, cancer, although more data are needed to discern
in contrast to nongestational breast cancers, at the the effects these have on overall disease progno-
time of diagnosis, gestational breast cancer is usually sis.105–108 Gestational breast cancer usually presents

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 Cancer and Pregnancy • CME Review Article 281

TABLE 2
Management of Other Hematologic Malignancies in Pregnancy
Hematologic Malignancy Maternal Management Delivery Implications
Acute promyelocytic leukemia Increased risk for DIC81 Consider termination if diagnosed in first
Treat with Anthracycline in first trimester* trimester
and ATRA in second/third trimester81,90
Chronic leukemia If leukocytosis severe, can use Can usually deliver at term if disease is
(myeloid and lymphoid) leukaphoresis82 stable
Imatinab appears teratogenic81
Interferon alpha promising as safe in early
studies91
Multiple myeloma Glucocorticoids to control disease burden Consider early delivery if diagnosed in third
Aggressive fluid hydration trimester92,93
Non Hodgkin’s lymphoma† Initiate treatment immediately75,94 Consider termination if diagnosed in first
Often involves the breast, the ovaries, trimester
the cervix, and the uterus Increased PPROM and preeclampsia rates87
Cyclophosphamide, doxorubicin,
vincristine, and prednisone95 used26
*If the patient does not desire termination, then anthracyclines should be used until the second trimester.
†Includes Burkitt lymphoma.
ATRA, all-trans retinoic acid; DIC, disseminated intravascular coagulation; PPROM, preterm premature rupture of membranes.

as a persistent, painless mass. It should be noted that evidence that, in these cases, adjuvant chemother-
the physiologic changes of breast architecture that apy can be used until delivery, with RT delayed until
occur during pregnancy make breast examination postpartum without affecting outcomes or recurrence
and breast imaging challenging to interpret.109,110 rates.118,125,126 For patients with higher-stage disease,
Despite this, any persistent mass should be evaluated chemotherapy is usually started. Common chemo-
with ultrasound because the risk for nodal metastatic therapies include doxorubicin and cyclophosphamide;
disease increases by almost 1% per month that a di- fluorouracil, doxorubicin, and cyclophosphamide; or
agnosis is delayed.111,112 Mammography, with ab- one of the taxanes.27,127 A recent literature review
dominal shielding, can also be used in pregnancy, suggested that, of these, the best data exist on the
although sensitivity is decreased.113–115 Limited data safety of taxanes for the mother and the fetus.128
exist on the specificity and sensitivity of breast MRI Other antineoplastic agents, including methotrexate,
during pregnancy. Diagnosis of gestational breast trastuzamab, and the selective estrogen receptor mod-
cancer is made with tissue biopsy, via either core ex- ulators, are contraindicated in pregnancy secondary
cisional biopsy or fine needle aspiration, both of to teratogenic effects on the fetus.17,75,119,129–131 Im-
which are safe during pregnancy.99,116 portantly, independent of which modality is selected,
After a tissue diagnosis of gestational breast cancer is treatment should not be postponed unless delivery is
made, the next step is a sentinel lymph node (SLN) bi- planned within 2 to 4 weeks of diagnosis.132 The most
opsy to begin the staging process. Recent studies have common pregnancy complication in women with ges-
confirmed that SLN biopsy is safe in pregnancy. 103,104 tational breast cancer is iatrogenic prematurity to fa-
Further staging with imaging is also necessary, al- cilitate maternal treatment. Delivery planning should
though in pregnancy, the studies vary to minimize radi- optimize maternal therapy while balancing the risks
ation exposure. Staging includes MRI of the head for of prematurity, and thus, delivery often occurs at ap-
brain metastasis, chest x-ray for lung metastasis, ab- proximately 37 weeks. This cancer can metastasize
dominal ultrasound for liver metastasis, and MRI for to the placenta, and postpartum pathologic evaluation
bone metastasis.4,117 A radionucleotide bone scan is recommended.38,39
may be necessary if the MRI is inconclusive.4 Surgical
treatment does not vary between gestational breast
Colon Cancer
cancer and breast cancer diagnosed outside pregnancy.
For regional disease, surgery, via either mastectomy or The incidence of colon cancer in pregnancy is 1 in
breast conservation surgery, can be performed safely 1300 to 16,000 pregnancies.76,133,134 During preg-
throughout pregnancy.118–122 If the patient elects to nancy, it is more common for cancers to involve
have breast conservation surgery, RT should be post- the rectum, compared with outside pregnancy where
poned until after delivery.116,123,124 There is good it is more common for the nonpelvic colon to be

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282 Obstetrical and Gynecological Survey

involved.76,133 There is no difference in stage at diag- The reported incidence of melanoma in pregnancy
nosis or survival for patients diagnosed with colon ranges from 2.8 to 5.0 per 100,000 pregnancies.150
cancer during pregnancy, although long-term sur- Women with a family history of melanoma, who ac-
vival for colon cancer is poor in general.135 During tively use/used tanning beds, who have had multiple
pregnancy, abdominal ultrasound is first line for di- severe sunburns during their lives, or with chronic
agnosis.132,136 However, as the uterus increases in immunosuppression are at increased risk for devel-
size, this is less accurate and MRI may be necessary. oping melanoma.120 Although increases in pigmenta-
Carcinoembryonic antigen levels are mildly elevated tion are normal during pregnancy, any nevus that
during normal pregnancy, and thus, this cannot be changes in size, color, or symmetry or becomes ir-
used as a screening tool for the gravid popula- regular should be further evaluated with biopsy.121
tion.137–139 Colonoscopy with biopsies as needed is A tissue sample is required to diagnose melanoma;
safe in pregnancy.140–142 usually, this is done with a biopsy. Staging with an
Similar to outside pregnancy, the treatment of co- SLN biopsy is the standard of care outside pregnancy
lon cancer depends on the stage of the disease. and should also be performed during pregnancy.
However, the trimester at diagnosis also affects the Multiple studies have demonstrated that the data
surgical field because a larger uterus may limit visu- obtained during a sentinel node biopsy outweigh the
alization of the affected colon. Similarly, if there is risks of radiation exposure to the fetus.117,122,125 Fur-
evidence of obstruction in the later trimesters, colos- ther staging with MRI or ultrasound of the chest, the
tomy may be necessary, whereas earlier in pregnancy, abdomen, the pelvis, and potentially the brain is an
primary resection is often possible.136,143 Metastatic important part of the workup as well.117 Initial treat-
disease to the ovaries is not uncommon. Oophorec- ment of melanoma does not differ in and out of preg-
tomy is safe in pregnancy but should be performed nancy. Lesions should be excised with wide margins
only for gross invasion on frozen section.94,143,144 as soon as possible and under local anesthesia when
When diagnosed later in pregnancy, surgery is often possible.126 Chemotherapy and interferon have been
postponed until 2 to 3 weeks postpartum, allowing used outside pregnancy. However, insufficient data
for the pelvic vessels and the uterus to decrease in size. exist to recommend the use of interferon during
Radiation is contraindicated during pregnancy.94,133,136 pregnancy.151
Chemotherapy, specifically 5-fluorouracil, may be When matched for tumor thickness and stage, mul-
used for higher-stage malignancy outside the first tri- tiple studies have shown no difference in overall sur-
mester. 5-fluorouracil is associated with fetal growth vival in women diagnosed during pregnancy and
restriction when used in pregnancy.22,127 Safety data those diagnosed outside pregnancy.130,152–155 How-
are very limited for irinotecan, oxaliplatin, capecitabine, ever, pregnancy does have a negative effect on the
and bevacizumab, and thus, these should be avoided stage of diagnosis, underlying the importance of ac-
if possible.134,145 tive management and a low threshold for biopsy of
Delivery timing varies by stage and gestational age any suspicious lesion during pregnancy. Melanoma
at diagnosis. Cases of healthy term infants after sur- metastasizes to the placenta more commonly than
gical intervention in early pregnancy have been re- any other malignancy.72 It also has the capability to
ported.118,146 Colon cancer has been associated with metastasize to the fetus.72 These are both more likely
an increase in spontaneous preterm birth, although to occur in patients with disseminated disease. Al-
overall fetal outcomes are very good.135 Vaginal deliv- though outcomes are very poor for both mother and
ery may be possible. However, cesarean delivery is the infant in these cases, maternal and fetal outcomes
preferred if a concomitant surgical resection is planned with stage I or II disease are very good.72,156,157
or if the vagina is obstructed by tumor. In addition, ce-
sarean delivery may be recommended if the tumor is
Thyroid Cancer
located on the anterior rectum and there is concern that
pressure, laceration, or episiotomy could lead to in- Thyroid cancer is one of the most common cancers
creased bleeding or tumor expansion133,136,146 Colon can- diagnosed during pregnancy, with an incidence of
cer has been reported to metastasize to the placenta.147 14 per 100,000.43 Most thyroid cancers diagnosed
during this time are papillary cancers.43 Interestingly,
thyroid nodules have been shown to increase as par-
Melanoma
ity increases.158,159 When a thyroid nodule is found
Melanoma is one of the most common cancers diag- on examination, the patient should be queried about
nosed in women during their reproductive years.148,149 a personal history of thyroid disease; ionizing

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 Cancer and Pregnancy • CME Review Article 283

radiation exposure; and family history of thyroid dis- the fetus when possible. At the same time, the most
ease, including familial polyposis, familial medullary important point of care should focus on maternal
carcinoma, and multiple endocrine neoplasia.160 Fur- survival.
ther evaluation includes a thyroid ultrasound and se-
rum thyroid-stimulating hormone and free thyroxine REFERENCES
levels.160
1. Pentheroudakis G, Pavlidis N. Cancer and pregnancy: poena
Concerning findings on ultrasound should prompt a magna, not anymore. Eur J Cancer. 2006;42:126–140.
fine needle aspiration, which is safe in pregnancy in- 2. Weisz B, Schiff E, Lishner M. Cancer in pregnancy: maternal
dependent of trimester.13,86,88 Stable tumors do not and fetal implications. Hum Reprod Update. 2001;7:384–393.
3. Antonelli NM, Dotters DJ, Katz VL, et al. Cancer in preg-
require surgery during pregnancy.160 However, if sur- nancy: a review of the literature. Part I. Obst Gynecol Surv.
gery is postponed, then thyroid ultrasound should be 1996;51:125–134.
repeated each trimester. An increase in volume by 4. Amant F, Deckers S, Van Calsteren K, et al. Breast cancer in
pregnancy: recommendations of an international consensus
50% and tumor diameter by 20% in 2 dimensions, meeting. Eur J Cancer. 2010;46:3158–3168.
or evidence of metastatic disease, are indications for 5. Brenner B, Avivi I, Lishner M. Haematological cancers in preg-
surgery.160–162 If thyroidectomy is deferred, thyroid nancy. Lancet. 2012;379:580–587.
6. Salani R, Billingsley CC, Crafton SM. Cancer and pregnancy:
hormone suppression can be used, with a postgoal an overview for obstetricians and gynecologists. Am J Obstet
thyroid-stimulating hormone in the low to normal Gynecol. 2013.
range (0.1–1.5 mU/L).137 7. The American College of Obstetricians and Gynecologists.
Guidelines for diagnostic imaging during pregnancy. Int J
Survival outcomes and recurrence rates for women Gynaecol Obstet. 1995;51:288–291.
with thyroid cancer do not differ between pregnant 8. Isla A, Alvarez F, Gonzalez A, et al. Brain tumor and preg-
and nonpregnant women.17,162–164 Delaying surgery nancy. Obstet Gynecol. 1997;89:19–23.
9. McTiernan AM, Weiss NS, Daling JR. Incidence of thyroid
until the postpartum period does not seem to adversely cancer in women in relation to reproductive and hormonal
affect maternal outcome. Some authors have noted factors. Am J Epidemiol. 1984;120:423–435.
higher rates of endocrine and surgical complications 10. Zwinkels H, Dorr J, Kloet F, et al. Pregnancy in women with
gliomas: a case-series and review of the literature. J Neurooncol.
when surgery is performed during pregnancy.16,17 De- 2013;115:293–301.
livery before term is almost never indicated in this 11. Zanotti-Fregonara P, Koroscil TM, Mantil J, et al. Radiation
population. Cesarean delivery should be performed dose to the fetus from [(18)F]-FDG administration during the sec-
ond trimester of pregnancy. Health Phys. 2012;102:217–219.
only for obstetric indications. Fetal outcomes are very 12. Blom JW, Doggen CJ, Osanto S, et al. Malignancies,
good and do not seem to be affected by thyroid can- prothrombotic mutations, and the risk of venous thrombosis.
cer during pregnancy, although data are limited.16 JAMA. 2005;293:715–722.
13. Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep
Radioablative therapy is contraindicated during preg- vein thrombosis and pulmonary embolism: a population-
nancy and breastfeeding.160 Overall, pregnancy and based case-control study. Arch Intern Med. 2000;160:809–815.
neonatal outcomes are minimally affected by thyroid 14. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsur-
gical patients: Antithrombotic Therapy and Prevention of
cancer.16,160 Thrombosis, 9th ed: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines. Chest. 2012;141
(suppl 2):e195S–e226S.
CONCLUSIONS 15. Mackenzie AP, Levine G, Garry D, et al. Glioblastoma multiforme
in pregnancy. J Matern Fetal Neonatal Med. 2005;17:81–83.
Cancer during pregnancy, although not common, 16. Kuy S, Roman SA, Desai R, et al. Outcomes following thyroid
poses a complicated situation, with many challenging and parathyroid surgery in pregnant women. Arch Surg.
2009;144:399–406; discussion 406.
diagnostic and therapeutic dilemmas for the patient 17. Tan GH, Gharib H, Goellner JR, et al. Management of
and her care team. Despite this, maternal outcomes thyroid nodules in pregnancy. Arch Intern Med. 1996;156:
are generally only minimally affected, if at all. Ultra- 2317–2320.
18. Ezri T, Szmuk P, Evron S, et al. Difficult airway in obstetric an-
sound and MRI are the mainstays of imaging during esthesia: a review. Obstet Gynecol Surv. 2001;56:631–641.
pregnancy. Other imaging may be used if necessary, 19. Gerstenfeld TS, Chang DT, Pliego AR, et al. Nonobstetrical
although radiation exposure to the fetus should be abdominal surgery during pregnancy in Women's Hospital. J
Matern Fetal Med. 2000;9:170–172.
minimized. When possible, surgery and chemother- 20. Maxwell C, Barzilay B, Shah V, et al. Maternal and neonatal
apy should be performed outside the first trimester. outcomes in pregnancies complicated by bone and soft-
Radiation therapy should be avoided in pregnancy. tissue tumors. Obstet Gynecol. 2004;104:344–348.
21. Doll DC, Ringenberg QS, Yarbro JW. Antineoplastic agents
Fetal outcomes are generally very good, with iatro- and pregnancy. Semin Oncol. 1989;16:337–346.
genic prematurity being the most common complica- 22. Zemlickis D, Lishner M, Degendorfer P, et al. Fetal outcome
tion. Optimal care of the pregnant mother with cancer after in utero exposure to cancer chemotherapy. Arch Intern
Med. 1992;152:573–576.
requires a multidisciplinary team, with a focus on 23. Cardonick E, Iacobucci A. Use of chemotherapy during hu-
maternal treatments while minimizing impact on man pregnancy. Lancet Oncol. 2004;5:283–291.

Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
284 Obstetrical and Gynecological Survey

24. Zemlickis D, Lishner M, Degendorfer P, et al. Maternal and 48. Merimsky O, Isakov J, Kollender Y, et al. Vascular invasion in
fetal outcome after breast cancer in pregnancy. Am J Obstet high grade sarcoma of the extremity is associated with short
Gynecol. 1992;166:781–787. overall survival. Oncol Rep. 1998;5:985–989.
25. Buekers TE, Lallas TA. Chemotherapy in pregnancy. Obstet 49. Stevenson CB, Thompson RC. The clinical management of in-
Gynecol Clin North Am. 1998;25:323–329. tracranial neoplasms in pregnancy. Clinical Obstet Gynecol.
26. Aviles A, Neri N. Hematological malignancies and pregnancy: 2005;48:24–37.
a final report of 84 children who received chemotherapy in 50. Burrow GN, Ferris TF. Medical Complications During Preg-
utero. Clin Lymphoma. 2001;2:173–177. nancy. 2nd ed. Philadelphia, PA: Saunders; 1982.
27. Hahn KM, Johnson PH, Gordon N, et al. Treatment of preg- 51. Tomson T, Landmark CJ, Battino D. Antiepileptic drug treat-
nant breast cancer patients and outcomes of children exposed ment in pregnancy: changes in drug disposition and their clin-
to chemotherapy in utero. Cancer. 2006;107:1219–1226. ical implications. Epilepsia. 2013;54:405–414.
28. Van Calsteren K, Berteloot P, Hanssens M, et al. In utero ex- 52. Sneed PK, Albright NW, Wara WM, et al. Fetal dose estimates
posure to chemotherapy: effect on cardiac and neurologic for radiotherapy of brain tumors during pregnancy. Int J
outcome. J Clin Oncol. 2006;24:e16–e17. Radiat Oncol Biol Phys. 1995;32:823–830.
29. Amant F, Van Calsteren K, Halaska MJ, et al. Gynecologic 53. Nishio S, Morioka T, Suzuki S, et al. Primary brain tumours
cancers in pregnancy: guidelines of an international consen- manifesting during pregnancy: presentation of six cases and
sus meeting. Int J Gynecol Cancer. 2009;19(suppl 1):S1–S12. a review of the literature. J Clin Neurosci. 1996;3:334–337.
30. Greskovich JF Jr, Macklis RM. Radiation therapy in preg- 54. Tewari KS, Cappuccini F, Asrat T, et al. Obstetric emergen-
nancy: risk calculation and risk minimization. Semin Oncol. cies precipitated by malignant brain tumors. Am J Obstet
2000;27:633–645. Gynecol. 2000;182:1215–1221.
31. Streffer C, Shore R, Konermann G, et al. Biological effects af- 55. Johnson N, Sermer M, Lausman A, et al. Obstetric outcomes
ter prenatal irradiation (embryo and fetus). A report of the In- of women with intracranial neoplasms. Int J Gynaecol Obstet.
ternational Commission on Radiological Protection. Ann 2009;105:56–59.
ICRP. 2003;33:5–206. 56. Wu J, Ma YH, Wang TL. Glioma in the third trimester of preg-
32. Kal HB, Struikmans H. Radiotherapy during pregnancy: fact nancy: two cases and a review of the literature. Oncol Lett.
and fiction. Lancet Oncol. 2005;6:328–333. 2013;5:943–946.
33. Abadi U, Koren G, Lishner M. Leukemia and lymphoma in preg- 57. Chaudhuri P, Wallenburg HC. Brain tumors and pregnancy.
nancy. Hematol Oncol Clin North Am. 2011;25:277–291, vii. Presentation of a case and a review of the literature. Eur J
34. Lew PS, Tan WC, Tan WK, et al. Dilemmas in management Obstet Gynecol Reprod Biol. 1980;11:109–114.
of brain tumours in pregnancy. Ann Acad Med Singapore. 58. Lee LS, Chi CW, Chang TJ, et al. Steroid hormone receptors
2010;39:64–65. in meningiomas of Chinese patients. Neurosurgery. 1989;
35. McGrane J, Bedford T, Kelly S. Successful pregnancy and de- 25:541–545.
livery after concomitant temozolomide and radiotherapy treat- 59. Lynch JC, Gouvea F, Emmerich JC, et al. Management strat-
ment of glioblastoma multiforme. Clin Oncol (R Coll Radiol). egy for brain tumour diagnosed during pregnancy. Br J
2012;24:311. Neurosurg. 2011;25:225–230.
36. Merimsky O, Le Chevalier T, Missenard G, et al. Management 60. Pallud J, Duffau H, Razak RA, et al. Influence of pregnancy in
of cancer in pregnancy: a case of Ewing’s sarcoma of the pel- the behavior of diffuse gliomas: clinical cases of a French gli-
vis in the third trimester. Ann Oncol. 1999;10:345–350. oma study group. J Neurol. 2009;256:2014–2020.
37. Schur S, Wild J, Amann G, et al. Sarcoma of the ewing family 61. Roelvink NC, Kamphorst W, van Alphen HA, et al. Pregnancy-
in pregnancy: a case report of intrauterine fetal death after in- related primary brain and spinal tumors. Arch Neurol. 1987;
duction of chemotherapy. Case Rep Oncol. 2012;5:633–638. 44:209–215.
38. Dildy GA III, Moise KJ Jr, Carpenter RJ Jr, et al. Maternal 62. Azim HA Jr, Peccatori FA, Pavlidis N. Lung cancer in the
malignancy metastatic to the products of conception: a re- pregnant woman: to treat or not to treat, that is the question.
view. Obstet Gynecol Surv. 1989;44:535–540. Lung Cancer. 2010;67:251–256.
39. Sebire NJ, Jauniaux E. Fetal and placental malignancies: 63. Boussios S, Han SN, Fruscio R, et al. Lung cancer in preg-
prenatal diagnosis and management. Ultrasound Obstet nancy: report of nine cases from an international collaborative
Gynecol. 2009;33:235–244. study. Lung Cancer. 2013;82:499–505.
40. Moller D, Ipsen L, Asschenfeldt P. Fatal course of malig- 64. Garrido M, Clavero J, Huete A, et al. Prolonged survival of a
nant melanoma during pregnancy with dissemination to woman with lung cancer diagnosed and treated with chemo-
the products of conception. Acta Obstet Gynecol Scand. therapy during pregnancy. Review of cases reported. Lung
1986;65:501–502. Cancer. 2008;60:285–290.
41. Cramblett HG, Friedman JL, Najjar S. Leukemia in an infant born 65. Pavlidis NA. Coexistence of pregnancy and malignancy. On-
of a mother with leukemia. N Engl J Med. 1958;259:727–729. cologist. 2002;7:279–287.
42. Brodsky I, Baren M, Kahn SB, et al. Metastatic malignant mel- 66. Sariman N, Levent E, Yener NA, et al. Lung cancer and preg-
anoma from mother to fetus. Cancer. 1965;18:1048–1054. nancy. Lung Cancer. 2013;79:321–323.
43. Smith LH, Danielsen B, Allen ME, et al. Cancer associated 67. Stark P, Greene RE, Morgan G, Hildebrandt-Stark HE. Lung
with obstetric delivery: results of linkage with the California cancer and pregnancy. Radiologe. 1985;25:30–32.
cancer registry. Am J Obstet Gynecol. 2003;189:1128–1135. 68. Kamal Y, Sheehan S, Geary M. Gastric carcinoma: an unusual
44. Stensheim H, Moller B, van Dijk T, et al. Cause-specific cause of vomiting in pregnancy. J Obstet Gynaecol. 2004;
survival for women diagnosed with cancer during pregnancy 24:820.
or lactation: a registry-based cohort study. J Clin Oncol. 69. Sakamoto K, Kanda T, Ohashi M, et al. Management of
2009;27:45–51. patients with pregnancy-associated gastric cancer in Japan:
45. Haerr RW, Pratt AT. Multiagent chemotherapy for sarcoma di- a mini-review. Int J Clin Oncol. 2009;14:392–396.
agnosed during pregnancy. Cancer. 1985;56:1028–1033. 70. Jaspers VK, Gillessen A, Quakernack K. Gastric cancer in
46. Simon MA, Phillips WA, Bonfiglio M. Pregnancy and ag- pregnancy: do pregnancy, age or female sex alter the progno-
gressive or malignant primary bone tumors. Cancer. 1984; sis? Case reports and review. Eur J Obstet Gynecol Reprod
53:2564–2569. Biol. 1999;87:13–22.
47. Huvos AG, Butler A, Bretsky SS. Osteogenic sarcoma in preg- 71. Ueo H, Matsuoka H, Tamura S, et al. Prognosis in gastric
nant women. Prognosis, therapeutic implications, and litera- cancer associated with pregnancy. World J Surg. 1991;15:
ture review. Cancer. 1985;56:2326–2331. 293–297, discussion 298.

Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Cancer and Pregnancy • CME Review Article 285

72. Alexander A, Samlowski WE, Grossman D, et al. Metastatic 96. Andersson TM, Johansson AL, Hsieh CC, et al. Increasing in-
melanoma in pregnancy: risk of transplacental metastases cidence of pregnancy-associated breast cancer in Sweden.
in the infant. J Clin Oncol. 2003;21:2179–2186. Obstet Gynecol. 2009;114:568–572.
73. Reynoso EE, Shepherd FA, Messner HA, et al. Acute leuke- 97. Van Calsteren K, Heyns L, De Smet F, et al. Cancer during preg-
mia during pregnancy: the Toronto Leukemia Study Group nancy: an analysis of 215 patients emphasizing the obstetrical
experience with long-term follow-up of children exposed and the neonatal outcomes. J Clin Oncol. 2010; 28:683–689.
in utero to chemotherapeutic agents. J Clin Oncol. 98. Anderson BO, Petrek JA, Byrd DR, et al. Pregnancy influences
1987;5:1098–1106. breast cancer stage at diagnosis in women 30 years of age
74. Hurley TJ, McKinnell JV, Irani MS. Hematologic malignancies in and younger. Ann Surg Oncol. 1996;3:204–211.
pregnancy. Obstet Gynecol Clin North Am. 2005;32: 595–614. 99. Novotny DB, Maygarden SJ, Shermer RW, et al. Fine needle
75. Cullins SL, Pridjian G, Sutherland CM. Goldenhar’s syndrome aspiration of benign and malignant breast masses associated
associated with tamoxifen given to the mother during gesta- with pregnancy. Acta Cytol. 1991;35:676–686.
tion. JAMA . 1994;271:1905–1906. 100. Gentilini O, Cremonesi M, Toesca A, et al. Sentinel lymph
76. Mechery J, Ikhena SE. Cancer of the descending colon during node biopsy in pregnant patients with breast cancer. Eur J
pregnancy. J Obstet Gynaecol. 2007;27:311–312. Nucl Med Mol Imaging. 2010;37:78–83.
77. Molkenboer JF, Vos AH, Schouten HC, et al. Acute lympho- 101. Khera SY, Kiluk JV, Hasson DM, et al. Pregnancy-associated
blastic leukaemia in pregnancy. Neth J Med. 2005;63: 361–363. breast cancer patients can safely undergo lymphatic map-
78. Caligiuri MA, Mayer RJ. Pregnancy and leukemia. Semin ping. Breast J. 2008;14:250–254.
Oncol. 1989;16:388–396. 102. Elledge RM, Ciocca DR, Langone G, et al. Estrogen receptor,
79. Catanzarite VA, Ferguson JE II. Acute leukemia and preg- progesterone receptor, and HER-2/neu protein in breast
nancy: a review of management and outcome, 1972–1982. cancers from pregnant patients. Cancer. 1993;71:2499–2506.
Obstet Gynecol Surv. 1984;39:663–678. 103. Middleton LP, Amin M, Gwyn K, et al. Breast carcinoma in
80. Greenlund LJ, Letendre L, Tefferi A. Acute leukemia during pregnant women: assessment of clinicopathologic and immu-
pregnancy: a single institutional experience with 17 cases. nohistochemical features. Cancer. 2003;98:1055–1060.
Leuk Lymphoma. 2001;41:571–577. 104. Reed W, Hannisdal E, Skovlund E, et al. Pregnancy and
81. Rizack T, Mega A, Legare R, et al. Management of hematolog- breast cancer: a population-based study. Virchows Arch.
ical malignancies during pregnancy. Am J Hematol. 2009; 2003;443:44–50.
84:830–841. 105. Cullinane CA, Lubinski J, Neuhausen SL, et al. Effect of preg-
82. Ali R, Ozkalemkas F, Ozkocaman V, et al. Successful preg- nancy as a risk factor for breast cancer in BRCA1/BRCA2 mu-
nancy and delivery in a patient with chronic myelogenous leu- tation carriers. Int J Cancer. 2005;117:988–991.
kemia (CML), and management of CML with leukapheresis 106. Johannsson O, Loman N, Borg A, et al. Pregnancy-associ-
during pregnancy: a case report and review of the literature. ated breast cancer in BRCA1 and BRCA2 germline mutation
Jpn J Clin Oncol. 2004;34:215–217. carriers. Lancet. 1998;352:1359–1360.
83. Broccia G, Casula P, Andria M. Chronic myelocytic leukemia 107. Shen T, Vortmeyer AO, Zhuang Z, et al. High frequency of al-
in pregnancy: report of a case treated with leukapheresis. lelic loss of BRCA2 gene in pregnancy-associated breast car-
Tumori. 1984;70:371–374. cinoma. J Natl Cancer Inst. 1999;91:1686–1687.
84. Lishner M, Zemlickis D, Degendorfer P, et al. Maternal and 108. Loman N, Johannsson O, Kristoffersson U, et al. Family his-
foetal outcome following Hodgkin's disease in pregnancy. Br tory of breast and ovarian cancers and BRCA1 and BRCA2
J Cancer. 1992;65:114–117. mutations in a population-based series of early-onset breast
85. Ward FT, Weiss RB. Lymphoma and pregnancy. Semin cancer. J Natl Cancer Inst. 2001;93:1215–1223.
Oncol. 1989;16:397–409. 109. Scott-Conner CE, Schorr SJ. The diagnosis and management
86. Connors JM. Challenging problems: coincident pregnancy, of breast problems during pregnancy and lactation. Am J
HIV infection, and older age. Hematology Am Soc Hematol Surg. 1995;170:401–405.
Educ Program. 2008:334–339. 110. Woo JC, Yu T, Hurd TC. Breast cancer in pregnancy: a litera-
87. Evens AM, Advani R, Press OW, et al. Lymphoma occurring ture review. Arch Surg. 2003;138:91–98; discussion 99.
during pregnancy: antenatal therapy, complications, and ma- 111. Nettleton J, Long J, Kuban D, et al. Breast cancer during
ternal survival in a multicenter analysis. J Clin Oncol. 2013; pregnancy: quantifying the risk of treatment delay. Obstet
31:4132–4139. Gynecol. 1996;87:414–418.
88. Pereg D, Koren G, Lishner M. The treatment of Hodgkin’s and 112. Ulery M, Carter L, McFarlin BL, et al. Pregnancy-associated
non-Hodgkin’s lymphoma in pregnancy. Haematologica. breast cancer: significance of early detection. J Midwifery
2007;92:1230–1237. Womens Health. 2009;54:357–363.
89. Bachanova V, Connors JM. Hodgkin lymphoma in pregnancy. 113. Ishida T, Yokoe T, Kasumi F, et al. Clinicopathologic charac-
Curr Hematol Malig Rep. 2013;8:211–217. teristics and prognosis of breast cancer patients associated
90. Shapira T, Pereg D, Lishner M. How I treat acute and chronic with pregnancy and lactation: analysis of case-control study
leukemia in pregnancy. Blood Rev. 2008;22:247–259. in Japan. Jpn J Cancer Res. 1992;83:1143–1149.
91. Mubarak AA, Kakil IR, Awidi A, et al. Normal outcome of preg- 114. Liberman L, Giess CS, Dershaw DD, et al. Imaging of pregnancy-
nancy in chronic myeloid leukemia treated with interferon- associated breast cancer. Radiology. 1994;191:245–248.
alpha in 1st trimester: report of 3 cases and review of the 115. Samuels TH, Liu FF, Yaffe M, et al. Gestational breast cancer.
literature. Am J Hematol. 2002;69:115–118. Can Assoc Radiol J. 1998;49:172–180.
92. Kasenda B, Ruckert A, Farthmann J, et al. Management of 116. Dominici LS, Kuerer HM, Babiera G, et al. Wound com-
multiple myeloma in pregnancy: strategies for a rare chal- plications from surgery in pregnancy-associated breast can-
lenge. Clin Lymphoma Myeloma Leuk. 2011;11:190–197. cer (PABC). Breast Dis. 2010;31:1–5.
93. Dabrowska DM, Gore C, Griffiths S, et al. Anaesthetic man- 117. Nicklas AH, Baker ME. Imaging strategies in the pregnant
agement of a pregnant patient with multiple myeloma. Int J cancer patient. Semin Oncol. 2000;27:623–632.
Obstet Anesth. 2010;19:336–339. 118. Rojansky N, Shushan A, Livni N, et al. Pregnancy associated
94. Bernstein MA, Madoff RD, Caushaj PF. Colon and rectal with colon carcinoma overexpressing p53. Gynecol Oncol.
cancer in pregnancy. Dis Colon Rectum. 1993;36:172–178. 1997;64:516–520.
95. Lambe M, Hsieh C, Trichopoulos D, et al. Transient increase 119. Tewari K, Bonebrake RG, Asrat T, et al. Ambiguous genitalia
in the risk of breast cancer after giving birth. N Engl J Med in infant exposed to tamoxifen in utero. Lancet. 1997;
1994;331:5–9. 350:183.

Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
286 Obstetrical and Gynecological Survey

120. Kincannon J, Boutzale C. The physiology of pigmented nevi. 142. Minter A, Malik R, Ledbetter L, et al. Colon cancer in preg-
Pediatrics. 1999;104(pt 2):1042–1045. nancy. Cancer Control: Journal of the Moffitt Cancer Center.
121. Goldstein BG, Goldstein AO. Diagnosis and management 2005;12:196–202.
of malignant melanoma. Am Fam Physician. 2001;63:1359– 143. Walsh C, Fazio VW. Cancer of the colon, rectum, and anus
1368, 1374. during pregnancy. The surgeon’s perspective. Gastroenterol
122. Keleher A, Wendt R III, Delpassand E, et al. The safety of lym- Clin North Am. 1998;27:257–267.
phatic mapping in pregnant breast cancer patients using 144. Antonelli NM, Dotters DJ, Katz VL, et al. Cancer in pregnancy:
Tc-99m sulfur colloid. Breast J. 2004;10:492–495. a review of the literature. Part II. Obstet Gynecol Surv.
123. Annane K, Bellocq JP, Brettes JP, et al. Infiltrative breast can- 1996;51:135–142.
cer during pregnancy and conservative surgery. Fetal Diagn 145. Taylor J, Amanze A, Di Federico E, et al. Irinotecan use during
Ther. 2005;20:442–444. pregnancy. Obstet Gynecol. 2009;114(pt 2):451–452.
124. Kuerer HM, Gwyn K, Ames FC, et al. Conservative surgery 146. Ochshorn Y, Kupferminc MJ, Lessing JB, et al. Rectal carci-
and chemotherapy for breast carcinoma during pregnancy. noma during pregnancy: a reminder and updated treatment
Surgery. 2002;131:108–110. protocols. Eur J Obstet Gynecol Reprod Biol. 2000;91:201–202.
125. Mondi MM, Cuenca RE, Ollila DW, et al. Sentinel lymph node 147. Rothman LA, Cohen CJ, Astarloa J. Placental and fetal in-
biopsy during pregnancy: initial clinical experience. Ann Surg volvement by maternal malignancy: a report of rectal carci-
Oncol. 2007;14:218–221. noma and review of the literature. Am J Obstet Gynecol.
126. Rosenberg PH, Veering BT, Urmey WF. Maximum rec- 1973;116:1023–1034.
ommended doses of local anesthetics: a multifac- 148. Bleyer A, Viny A, Barr R. Cancer in 15- to 29-year-olds by pri-
torial concept. Reg Anesth Pain Med. 2004;29:564–575; mary site. Oncologist. 2006;11:590–601.
discussion 524. 149. Weir HK, Marrett LD, Cokkinides V, et al. Melanoma in
127. Berry DL, Theriault RL, Holmes FA, et al. Management of adolescents and young adults (ages 15–39 years): United States,
breast cancer during pregnancy using a standardized proto- 1999–2006. J Am Acad Dermatol. 2011;65(suppl 1):S38–S49.
col. J Clin Oncol. 1999;17:855–861. 150. Dillman RO, Vandermolen LA, Barth NM, et al. Malignant mel-
128. Mir O, Berveiller P, Goffinet F, et al. Taxanes for breast cancer anoma and pregnancy ten questions. West J Med. 1996;
during pregnancy: a systematic review. Ann Oncol. 2010;21: 164:156–161.
425–426. 151. Beyeler M, Hafner J, Beinder E, et al. Special considerations
129. Isaacs RJ, Hunter W, Clark K. Tamoxifen as systemic treat- for stage IV melanoma during pregnancy. Arch Dermatol.
ment of advanced breast cancer during pregnancy—case re- 2005;141:1077–1079.
port and literature review. Gynecol Oncol. 2001;80:405–408. 152. Karagas MR, Zens MS, Stukel TA, et al. Pregnancy history
130. O’Meara AT, Cress R, Xing G, et al. Malignant melanoma and incidence of melanoma in women: a pooled analysis.
in pregnancy. A population-based evaluation. Cancer. 2005; Cancer Causes Control. 2006;17:11–19.
103:1217–1226. 153. Lens MB, Rosdahl I, Ahlbom A, et al. Effect of pregnancy on
131. Zagouri F, Sergentanis TN, Chrysikos D, et al. Trastuzumab ad- survival in women with cutaneous malignant melanoma. J
ministration during pregnancy: a systematic review -and meta- Clin Oncol. 2004;22:4369–4375.
analysis. Breast Cancer Res Treat. 2013; 137:349–357. 154. MacKie RM, Bufalino R, Morabito A, et al. Lack of effect of preg-
132. Jones AL. Management of pregnancy-associated breast can- nancy on outcome of melanoma. For The World Health Organi-
cer. Breast. 2006;15(suppl 2):S47–S52. sation Melanoma Programme. Lancet. 1991;337:653–655.
133. Longo SA, Moore RC, Canzoneri BJ, et al. Gastrointestinal 155. McManamny DS, Moss AL, Pocock PV, et al. Melanoma and
conditions during pregnancy. Clin Colon Rectal Surg. 2010; pregnancy: a long-term follow-up. Br J Obstet Gynaecol.
23:80–89. 1989;96:1419–1423.
134. Saif MW. Management of colorectal cancer in pregnancy: 156. Baergen RN, Johnson D, Moore T, et al. Maternal melanoma
a multimodality approach. Clin Colorectal Cancer. 2005;5: metastatic to the placenta: a case report and review of the lit-
247–256. erature. Arch Pathol Lab Med. 1997;121:508–511.
135. Dahling MT, Xing G, Cress R, et al. Pregnancy-associated co- 157. Gottschalk N, Jacobs VR, Hein R, et al. Advanced metastatic
lon and rectal cancer: perinatal and cancer outcomes. J melanoma during pregnancy: a multidisciplinary challenge.
Matern Fetal Neonatal Med. 2009;22:204–211. Onkologie. 2009;32:748–751.
136. Lolis ED, Likoudis P, Voiniadis P, et al. Synchronous rectal 158. Kung AW, Chau MT, Lao TT, et al. The effect of pregnancy on
and colon cancer caused by familial polyposis coli during thyroid nodule formation. J Clin Endocrinol Metabo. 2002;
pregnancy. J Obstet Gynaecol Res. 2007;33:199–202. 87:1010–1014.
137. Cooper DS. Thyroid hormone treatment: new insights into an 159. Struve CW, Haupt S, Ohlen S. Influence of frequency of previous
old therapy. JAMA. 1989;261:2694–2695. pregnancies on the prevalence of thyroid nodules in women
138. Lamerz R, Ruider H, et al. Significance of CEA determinations without clinical evidence of thyroid disease. Thyroid. 1993;3:7–9.
in patients with cancer of the colon-rectum and the mammary 160. Stagnaro-Green A, Abalovich M, Alexander E, et al. Guide-
gland in comparison to physiological states in connection lines of the American Thyroid Association for the diagnosis
with pregnancy. Bull Cancer. 1976.63:575–586. and management of thyroid disease during pregnancy and
139. Saif MW. Management of colorectal cancer in pregnancy: postpartum. Thyroid. 2011;21:1081–1125.
a multimodality approach. Clin Colorectal Cancer. 2005;5: 161. Mazzaferri EL. Approach to the pregnant patient with thyroid
247–256. cancer. J Clin Endocrinol Metab. 2011;96:265–272.
140. Nies C, Leppek R, Sitter H, et al. Prospective evaluation of dif- 162. Moosa M, Mazzaferri EL. Outcome of differentiated thyroid
ferent diagnostic techniques for the detection of liver metasta- cancer diagnosed in pregnant women. J clin endocrinol metab.
ses at the time of primary resection of colorectal carcinoma. 1997;82:2862–2866.
Eur J Surg. 1996;162:811–816. 163. Nam KH, Yoon JH, Chang HS, et al. Optimal timing of surgery
141. Seidman DS, Ben-Ari GY, Heyman Z, et al. Use of magnetic in well-differentiated thyroid carcinoma detected during preg-
resonance imaging in pregnancy to diagnose intussuscep- nancy. J Surg Oncol. 2005;91:199–203.
tion induced by colonic cancer. Obstet Gynecol. 1992;79: 164. Yasmeen S, Cress R, Romano PS, et al. Thyroid cancer in
822–823. pregnancy. Int J Gynaecol Obstet. 2005;91:15–20.

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