Case Reports in Women's Health 34 (2014) 79

Contents lists available at ScienceDirect

Case Reports in Women's Health

journal homepage: www.elsevier.com/locate/crwh

Breast Cancer in Pregnancy

Olivia Dziadek a, Paul Singh b,
a
b

University of Missouri Kansas City School of Medicine, Department of Obstetrics and Gynecology, United States
University of Missouri Kansas City School of Medicine, Department of Obstetrics and Gynecology, Division of MaternalFetal Medicine, United States

a r t i c l e

i n f o

Article history:
Received 13 June 2014
Received in revised form 31 July 2014
Accepted 1 August 2014
Available online 19 August 2014
Keywords:
Breast cancer
Pregnancy
Chemotherapy

1. Introduction
Pregnancy-associated breast cancer is dened as breast cancer diagnosed during pregnancy or in the rst postpartum year. It is the most
common cause of invasive cancer in pregnant women and is estimated
to occur at a rate of 6.5 per 100,000 live births [1,2]. According to a case
control study from Princess Margaret Hospital, pregnant patients are at
higher risk for presenting with advanced disease because pregnancy
impedes early detection [3]. Risk factors for pregnancy-associated
breast cancer include early age of menarche, nulliparity, personal history of breast cancer, advanced maternal age, family history of breast cancer, increased consumption of alcohol, obesity and a sedentary lifestyle
[4]. Of interest to Obstetricians is the management of breast cancer in
pregnancy. The timing of delivery should take into account maternal
and fetal status as well as need for further chemotherapy and expected
perinatal outcome while the mode of delivery should be determined by
standard obstetrical indications [5]. In an article by Trichopoulos et al.,
full term births over the age of 35 years had an increased risk in the development of breast cancer; uniparous women were observed to have
an elevated risk of breast cancer soon after delivery, specically those
women who are 30 years or older at the time of their rst delivery [6].
We present a case of premenopausal invasive ductal carcinoma of the
breast diagnosed during pregnancy, and review the literature regarding
the antenatal management of breast cancer.
Corresponding author at: UMKC School of Medicine, Dept. of Obstetrics and
Gynecology, 2301 Holmes Street, Kansas City, Missouri 64108, United States. Tel.: +1
816 590 4774; fax: +1 816 404 5152.
E-mail address: oliviadziadek@gmail.com (P. Singh).

1.1. Case Description

A 29 year old multiparous Hispanic female presented to our routine
obstetrical clinic at 7 weeks gestation. She had a past medical history
signicant for morbid obesity and poorly controlled type 2 diabetes
mellitus with a hemoglobin A1C of 10.7. On physical exam, the patient
was noted to have a left breast mass at the 11 o'clock position. Otherwise both breasts appeared symmetrical with no signs of skin changes
or lymphadenopathy. Similarly, both nipples and areola had no abnormal ndings. A breast ultrasound was performed and demonstrated a
4.5 2.6 3.2 cm mass that was irregular and hypoechoic consistent
with BIRADS 4 classication. A core needle biopsy was performed and
revealed invasive ductal carcinoma that was estrogen and progesterone
receptor positive and HER2 negative. The patient underwent a left modied radical mastectomy with left axillary lymph node dissection. Final
pathology conrmed invasive ductal carcinoma of the left breast, staged
at T3N2MX with ER and PR positivity in 80% and 70% of the tumor cells
respectively. The patient was treated with a combination of 4 cycles of
doxorubicin and cyclophosphamide during the second and third trimester. At 37 weeks gestation she was diagnosed with preeclampsia
and underwent delivery. A repeat cesarean section along with a riskreducing bilateral salpingo-oophorectomy was performed. Postoperatively a chest and abdomino-pelvic computed tomography as well as a
brain MRI were performed and showed no evidence of metastases.
Weekly paclitaxel was started on post-operative day 7 and was continued for 3 months.
The patient has also completed radiation to the chest wall and nodal
areas. Currently, the patient has completed 12 cycles of paclitaxel and
4 cycles of doxorubicin & cyclophosphamide. A CT of the chest, abdomen and pelvis was performed and revealed no evidence of disease.
BRCA testing is pending.
2. Discussion
The care of a pregnant patient with breast cancer involves the utilization of a multidisciplinary team, including a geneticist, obstetrician,
maternalfetal medicine specialist, medical oncologist, surgical oncologist and neonatologist. Early ultrasound dating should be obtained in
order to provide adequate counseling regarding pregnancy management. In addition, a detailed fetal anatomic evaluation during the mid
second trimester is recommended to exclude pre-existing fetal anomalies
[4]. The safest interval for most cancer therapies in pregnancy is between
the second and third trimesters, avoiding induction of teratogenic risks or
miscarriages [4]. If growth restriction or non-reassuring fetal status is

http://dx.doi.org/10.1016/j.crwh.2014.08.002
2214-9112/ 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

O. Dziadek, P. Singh / Case Reports in Women's Health 34 (2014) 79

Table 1
Chemotherapy: Maternal and fetal effects, JOGC [23].
Agent

Maternal

Fetal

Alkylating agents:
Cyclophosphamide

Myelosupression

Melphalan

Myelosuppresion, ovarian failure,

amenorrhea
Myelosuppression, Neurotoxicity
Cardiac dysfunction, arrhythmias

First trimester exposure: Oculofacial abnormalities, missing digits, nail malformations, coronary artery defects,
umbilical hernia, hemangioma, imperforate anus, rectovaginal stula, cleft palet, microcephaly, growth
restriction, developmental delays
Second trimester exposure: growth restriction, microcephaly, neonatal pancytopenia
No link with congenital defects

Taxanes: Paclitaxel
Trastuzumab
(Herceptin)
Vinblastine
Vinorelbine
5-Fluorouracil

Myelosuppression, Neurotoxicity

Methotrexate

Myelosuppression
Myelosuppresion, mucositis,
diarrhea, hand-foot syndrome
Myelosuppresion, acute renal failure

Doxorubicin

Myelosuppresion, cardiac toxicity

Few case reports of fetal exposure: no reported defects

Decreased amniotic uid, kidney defects
First trimester: normal outcomes, with three reported cases of suspected teratogenicity with hydrocephalus
after rst trimester exposure, cleft lip/palate
Sparse data available
First trimester: Radial dysplasia, absent digits, hypoplasias of thoracic and abdominal organs such as lungs,
aorta, esophagus, duodenum, ureters
First trimester: cephalic and skull abnormalities, absence of frontal bones, hypertelorism, depressed or
widened nasal bridge, hypoplasia of the mandible, heart defects, absence of digits
First trimester: Imperforate anus, rectovaginal stula, microcephaly

discovered, these conditions should be managed according to standard

obstetrical guidelines. The timing of delivery should take into account
maternal and fetal status as well as need for further chemotherapy
and expected perinatal outcome, while the mode of delivery should
be determined by standard obstetrical indications [5]. Chemotherapy
during pregnancy should not be given within 3 weeks of planned
delivery in order to avoid problems associated with maternal and
fetal myelosuppression [1214]. Chemotherapy and radiation may be
started immediately following a vaginal delivery and one week after
cesarean section [7]. Breastfeeding is contraindicated during treatment
with chemotherapy or radiation therapy [7].
If breast cancer is discovered during pregnancy, diagnostic and staging evaluations can be modied to limit fetal exposure [8]. The search
for distant metastases may be performed using ultrasonography and
MRI [8]. Mastectomy may be performed without fetal injury or spontaneous abortion [8]. Generally breast surgeons prefer to wait until after
the rst trimester due to the increased risk of spontaneous abortion associated with rst trimester surgical intervention, although women
who undergo surgery for breast cancer in the rst trimester do not
seem to have a higher rate of spontaneous loss compared with the
general population [9]. Both mastectomy and breast-conserving surgery
with axillary lymph node dissection are surgical options for pregnancyassociated breast cancer [8]. Mastectomy is sometimes preferred for
breast cancer in pregnancy since follow-up radiation therapy is typically
not required post-operatively.
Isosulfan blue or methylene blue dye lymph node mapping is not
recommended in pregnant women because anaphylaxis has been observed [8]. Technetium-based sentinel node identication, however,
has been performed safely in pregnancy [8]. Doxorubicin and cyclophosphamide (AC regiment) as well as 5-uorouracil, doxorubicin,
and cyclophosphamide (FAC regimen) may be administered during
the second and third trimesters for pregnancy-associated breast cancer;
Hahn et al. reported on 40 cases of fetuses exposed to the FAC regimen
and found that all women delivered live births and only 3 had congenital malformations [9].
In addition, Cardonick et al. reviewed 104 patients that received antenatal chemotherapy for breast cancer and demonstrated a 3.8% birth
defect rate [9]. Taxanes may also be used in pregnancy; Mir et al. published a systematic review of 40 patients regarding taxane use in pregnancy and only reported one case of pyloric stenosis [10]. For patients
with hormone receptor negative breast cancer, dose-dense chemotherapy regimens have demonstrated improved disease-free survival over
conventional dose chemotherapy in non-pregnant patients. Currently,

however, the data on dose-dense chemotherapeutic agents in pregnancy is limited and should not be administered for pregnancy-associated
breast cancer; Trastuzumab is a well-known treatment for HER2-positive breast cancer. However, if trastuzumab must be used, it should be
administered for as short of a duration as possible and surveillance of
amniotic uid levels and fetal growth should be performed [11] due to
risk for oligohydramnios. Data regarding the safety of Trastuzumab in
pregnancy is lacking. Therapy with selective estrogen receptor modulators, such as tamoxifen, in patients with hormone receptor positive
pregnancy-associated breast cancer should be deferred until after delivery due to risks associated with craniofacial malformations and ambiguous genitalia [12]. Supportive oncological agents such as ondansetron,
promethazine granulocyte colony-stimulating growth factor and erythropoietin may be safely administered during pregnancy (Table 1).
The prognostic outcome in women diagnosed with breast cancer
during pregnancy is conicting. Rodriquez et al. reviewed 797 patients
with pregnancy-associated breast cancer and compared them to 4177
non-pregnant breast cancer controls [15]; after controlling for stage of
disease, size of tumor, hormone receptor status, age, race, and type of
surgery, pregnancy-associated breast cancer survival was worse compared to the non-pregnant breast cancer cohort. On the other hand,
Beadle et al. evaluated 652 women with pregnancy-associated breast
cancer and found no statistically signicant difference in rates of recurrence, distant metastasis or overall survival compared to women who
did not have pregnancy-associated breast cancer [16].
Both prospective casecontrol and cohort studies have reported a
20%40% decreased risk of breast cancer in premenopausal obese
patients compared to normal weight controls [17,1820]. Recently,
however, Cecchini et al. reported data taken from the Breast Cancer Prevention Trial (BCPT) that showed that an increased risk of invasive
breast cancer was noted in overweight and obese premenopausal patients compared to patients of normal weight [21]. In addition, they
found only a slightly increased risk of invasive breast cancer among
the overweight and obese postmenopausal women in both the BCPT
and the Study of Tamoxifen and Raloxifene (STAR) trials. The potential
of obesity to mitigate breast cancer risk in both premenopausal and
postmenopausal patients seems to be inuenced by hormone receptor
status; for example, a stronger inverse association between obesity
and premenopausal estrogen and progesterone receptor positive
(ER +/PR +) breast cancer has been observed compared to ER-/PRcases [19]. Yang et al. recently found that obesity was more frequently associated with receptor ER-/PR- breast cancer compared with
receptor positive disease in women 50 years old or younger but

O. Dziadek, P. Singh / Case Reports in Women's Health 34 (2014) 79

was more frequent only in patients with PR + postmenopausal

breast cancers [22].
3. Conclusion
An awareness of risk factors for the development of breast cancer in
pregnant patients is critical to early diagnosis and treatment of breast
cancer. A breast exam should be performed early in pregnancy if possible, and if exam is performed later in pregnancy, one should exercise
vigilance regarding ndings. A careful review of chemotherapeutics
and their maternal as well as fetal effects should be instituted in a
new diagnosis of breast cancer, with close coordination of care among
specialists with the patient.
Disclosure Statement
No competing nancial conicts exist for any authorinvestigator.
References
[1] Abenhaim HA, et al. Incidence, risk factors, and obstetrical outcomes of women with
breast cancer in pregnancy. Breast J 2012;18(6):5648.
[2] Smith LH, et al. Cancer associated with obstetric delivery: results of linkage with the
California cancer registry. Am J Obstet Gynecol 2003;189(4):112835.
[3] Gabbe Steven G. Obstetrics: normal and problem pregnancies, fth addition.
Philadelphia, PA: Elsevier; 2007.
[4] American Cancer Society. What are the risks for breast cancer? www.cancer.org; 11
September 2013. [Website accessed: 20 July 2014].
[5] Sinicrope FA, Dannenberg AJ. Obesity and breast cancer prognosis: weight of the evidence. J Clin Oncol 2011;29(1):47.
[6] Trichopoulos D, Hsieh CC, MacMahon B, Lin TM, Lowe CR, Mirra AP, Ravnihar B,
Salber EJ, Valaoras VG, Yuasa S. Age at any birth and breast cancer risk. International
Journal of Cancer 1983;31:7014.

[7] Amant F, et al. Breast cancer in pregnancy. Lancet 2012;379(9815):5709.

[8] Berry D, et al. Management of breast cancer during pregnancy using a standardized
protocol. J Clin Oncol March 1999;17(3):85561.
[9] Hahn KM, et al. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer 2006;107(6):121926.
[10] Cardonick E, et al. Breast cancer during pregnancy: maternal and fetal outcomes.
Cancer J 2010;16(1):7682.
[11] Mir O, et al. Taxanes for breast cancer during pregnancy: a systematic review. Ann
Oncol 2010;21(2):4256.
[12] Federal drug administration. Trastuzumab. http://fda.gov/AboutFDA/CentersOfces/
OfceofMedicalProductsandTobacco/CDER/ucm231970.htm; 02 November 2010.
[Website accessed 28 July 2014].
[13] Tewari K, Bonebrake RG, Asrat T, Shanberg AM. Ambiguous genitalia in infant exposed to tamoxifen in utero. Lancet 1997;350:183.
[14] Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. J Clin Oncol 2002;20(4):112843.
[15] Sestak I, et al. Effect of body mass index on recurrences in tamoxifen and anastrozole
treated women: an exploratory analysis from the ATAC trial. J Clin Oncol 2010;
28(21):34115.
[16] Rodriguez AO, et al. Evidence of poorer survival in pregnancy-associated breast cancer. Obstet Gynecol 2008;112(1):718.
[17] Ogundiran TO, et al. Casecontrol study of body size and breast cancer risk in
Nigerian women. Am J Epidemiol 2010;172(6):68290.
[18] Rowland ML. Self-reported weight and height. Am J Clin Nutr 1990;52(6):112533.
[19] Harris HR, et al. Body fat distribution and risk of premenopausal breast cancer in the
Nurses' Health Study II. J Natl Cancer Inst 2011;103(3):2738.
[20] John EM, et al. Adult body size, hormone receptor status, and premenopausal breast
cancer risk in a multiethnic population: the San Francisco Bay Area breast cancer
study. Am J Epidemiol 2011;173(2):20116.
[21] Reeves GK, et al. Cancer incidence and mortality in relation to body mass index in
the Million Women Study: cohort study. BMJ 2007;335(7630):1134.
[22] Cecchini RS, et al. Body mass index and the risk for developing invasive breast cancer
among high-risk women in NSABP P-1 and STAR breast cancer prevention trials.
Cancer Prev Res (Phila) 2012;5(4):58392.
[23] Yang XR, et al. Associations of breast cancer risk factors with tumor subtypes: a
pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer
Inst 2011;103(3):25063.