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Pregnancy‑associated breast cancer:
Controversies and consensus!
T
he term pregnancy‑associated breast
cancer (PABC) refers to all breast cancers
diagnosed during pregnancy up to 1 year
following delivery. PABC accounts for
approximately 2% of primary breast cancer
patients.[1‑4]
The incidence of breast cancer is rising in India
and all over the world. This is anticipated
to lead to an increased proportion of breast
cancer in pregnant women. One of the primary
reasons for this is that women tend to postpone
childbearing to their thirties.[2‑4] The median
age of women diagnosed with PABC is below
35 years.[3] However, the biology of breast cancer
in very young women has a more aggressive
phenotype.[5,6]
The physiological changes associated with
normal pregnancy include increase in plasma
and red cell volume, physiological anemia,
increase in cardiac output, stroke volume,
and heart rate and tidal volume.[7,8] There is
increased blood flow to kidneys, liver, and most
organs. Changes in hematological system are
hypercoagulability and alteration in absolute
blood cell counts. Gastrointestinal symptoms
are nausea, vomiting in early pregnancy and
delayed gastric emptying, and constipation in
later parts of gestation. Overall pregnancy is a
hyperdynamic state and alters the dynamics of
drugs administered. This will have an effect on
treatment, side effects, monitoring of disease, and
oncological outcomes.[9,10]
complicate the whole scenario even further. The
treating physician should aim at understanding
the underlying issues, minimize harm, follow
best possible scientific evidence, and also be
aware of gaps in available evidence. It is very
important to include the pregnant lady and
her family at every stage of management and
adequate information and support given to them.
The key to understanding teratogenic effects is
to know the dynamics of substances that cross
placental barrier such as molecular weight,
protein binding, and bioavailability to the fetus.
Chemotherapeutic agents as well as drugs used
for treating side effects of chemotherapy and
perioperative medication should be screened
for potential teratogenic effects.[12] Radiation
exposure of the fetus either during investigations
or treatment definitely contributes to teratogenic
effects. Teratogenic effects are highest if the
fetus is exposed to any teratogen in the first
trimester. Other concerns during pregnancy
are intrauterine growth restriction, intrauterine
death, and preterm birth and are caused by
interaction of multiple factors related to host,
disease, and treatment.[13]
Future risk of cancer, genetic mutations, and
effect on IQ and learning is not well understood
and should not be underestimated. The
bioavailability of chemotherapeutic substances
in breast milk and functionality of the breast
for breastfeeding following surgery along with
psychological issues should be addressed.
General Principles of Management of
Pregnancy‑associated Breast Cancer
Principles of Management Specific to
Pregnancy‑associated Breast Cancer
There are standard international consensus
guidelines for management of breast cancer.
However, management of newly diagnosed
or recurrent breast cancer associated with
pregnancy is a sensitive issue and needs
multidisciplinary approach. There are many
factors which interact in this situation such as
highly increased endogenous hormone levels,
teratogenic effects of investigations and treatment
on the fetus, and safety of breastfeeding making it
a unique situation.[11] Emotional and body image
issues associated with diagnosis and treatment
Any suspicious breast lump should be biopsied
under local anesthesia during pregnancy.
Ultrasound is safe. Mammography and chest
X‑ray with adequate shielding of the abdomen
can be offered if necessary. Magnetic resonance
imaging is reserved for cases with metastatic
potential and should be used with caution as
gadolinium crosses the placenta. Bone scan is
reserved for suspected skeletal metastasis.[14]
© 2016 Oncobiology and Targets | Published by Wolters Kluwer - Medknow
Continuation or termination of pregnancy should
be discussed with care. Information on treatment
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Bajpai and Shylasree: Pregnancy and breast cancer
options based on stage of disease, teratogenicity of drugs, and
future fertility should be given before obtaining informed
consent. Management of pregnancy is similar to any high‑risk
pregnancy emphasizing on the multidisciplinary approach and
frequent monitoring of both mother and fetus/baby.
Stage versus stage, the management of breast cancer during
pregnancy is similar to nonpregnancy and should be managed
as closely as possible to standards for young, nonpregnant
women with breast cancer.[15,16]
Breast surgery is safe during pregnancy as long as blood
loss, maternal hypotension, and subsequent fetal hypoxia are
minimized. Standard guidelines for anesthesia and positioning
of the lady during surgery should be followed.[8] Precautions
for preventing deep vein thrombosis and antibiotic prophylaxis
should be taken. The physical and psychological effects of
surgical stress on pregnancy are not well understood, so
an effort to minimize stress wherever possible is desirable.
Maternal administration of tocolytic agents and antenatal
steroids for improving fetal lung maturity should be considered
in threatened preterm labor.
Due to detrimental effects of radiation on the fetus, radiation
therapy should be withheld until after delivery. Deferring
radiotherapy during pregnancy has not shown to worsen the
prognosis of the disease significantly.
Systemic Therapy in Pregnancy‑associated Breast
Cancer
Chemotherapy is contraindicated during the first trimester
due to potential teratogenicity with possible threefold rise in
congenital malformations. In subsequent trimesters, drugs
such as anthracyclines and taxanes are relatively safe and
should be offered as per standard protocols. However, regular
cardiac monitoring of mother and fetus is necessary to avoid
complications and fetal loss.
There are studies in small number of patients (84, 40, and 10),
wherein postchemotherapy exposure in utero, children were
found to have normal physical and mental development. In
a systematic review after taxane exposure in PABC patients,
healthy neonates were born, and 90% of those remain
completely healthy at a median follow‑up of 16 months.
The antimetabolite methotrexate (in the cyclophosphamide,
methotrexate, and 5‑fluorouracil regimen) is contraindicated
during pregnancy. Hence, safer regimens which can be
used are anthracycline based such as AC, EC, CAF, and
CEF (A‑adriamycin, E‑epirubicin, C‑cyclophosphamide, and
F‑5 Fluorouracil).[4,15,16]
International guidelines (ESMO and NCCN) suggest to
completely avoid the use of trastuzumab and lapatinib during
pregnancy due to the risk of oligo‑ and/or anhydramnios.
Inhibition of vascular endothelial growth factor which
regulates amniotic fluid circulation and Her2/neu on fetal renal
epithelium is the mechanism behind this side effect. The rate
of spontaneous miscarriage is also unacceptably increased to
around 25%. Drugs such as nab‑paclitaxel and antiangiogenic
drug bevacizumab and other anti‑her2 therapies are also not
2
recommended in PABC due to limited data and high risk of
complications.[15,16]
Hormonal agents such as tamoxifen affect the growing
embryonic tissues and can lead to abortions and congenital
abnormalities such as ambiguous genitalia and Goldenhar’s
syndrome. Therefore, adjuvant tamoxifen should be stated only
after delivery.[15,16] Breastfeeding is generally not recommended
when the patient is on chemotherapeutic agents.
Supportive Care
Granulocyte‑stimulating factors should be used only if
absolutely indicated (pregnancy category C); There are limited
data for the use of bisphosphonates in this situation.[15,16]
The consensus statement in most studies and international
panels reads as despite lack of long‑term follow‑up of children
exposed in utero to chemotherapy, in light of current existing
evidence, when indicated, physicians should not withhold
chemotherapy in the second and third trimester to improve
survival. However, one should optimize management so as
to save both precious lives together.[15,16]
Conclusion
PABC is a unique situation. As the incidence of PABC is
increasing, clinicians should be equipped with knowledge
to manage such women. Due to the lack of best‑quality
randomized evidence, clinical practice decisions are largely
guided by the evidence generated from retrospective analyses,
case reports, and a small number of prospective studies.
The management should be tailored according to the stage
of the pregnancy as well as the malignancy with critical
evaluation of the needs of the mother and risks to the fetus.
Anthracycline‑based chemotherapy appears safe during the
second and third trimesters; limited data demonstrate taxane
safety as well, weekly dosing is advantageous to allow closer
monitoring with prompt termination of therapy if need arises.
Surgery can be done in all trimesters; radiation and targeted
therapy (including hormone therapy) should be started after
delivery. Long‑term safety data of systemic therapy are sparse.
Standard consensus guidelines should be followed and the best
dealt with a multidisciplinary approach.
Jyoti Bajpai, T. S. Shylasree1
Departments of Medical Oncology and 1Surgical Oncology,
Tata Memorial Hospital, Mumbai, Maharashtra, India
Address for correspondence:
Dr. Jyoti Bajpai,
Department of Medical Oncology, Tata Memorial Hospital,
Mumbai ‑ 400 012, Maharashtra, India.
E‑mail: [email protected]
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How to cite this article: Bajpai J, Shylasree TS. Pregnancyassociated breast cancer: Controversies and consensus!. Oncobiol
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