Breast Cancer and Pregnancy: Why Special Considerations Before Treatment Are Essential

Table of Contents

• Key Points
• Why This Research Matters: Breast Cancer During Pregnancy
• Understanding the Biology of Pregnancy-Related Breast Cancer
• How Breast Cancer Is Diagnosed and Staged During Pregnancy
• Monitoring the Health of Both Mother and Baby
• Understanding the Risks of Anesthesia
• Treatment Options During Pregnancy: An Overview
• Surgery During Pregnancy
• Systemic Treatments: Chemotherapy, Targeted Therapy, and More
• What This Means for Patients
• What This Review Could Not Answer
• Recommendations for Patients and Families
• Frequently Asked Questions
• Source Information

Key Points

• Breast cancer affects about 1 in 1,000 pregnancies; any breast mass lasting over 2 weeks should be evaluated.
• Surgery for breast cancer is safe in all trimesters; reconstruction should wait until after birth.
• Chemotherapy is avoided in the first trimester but can be given later; last dose at least 3 weeks before delivery.
• Tamoxifen, trastuzumab, pertuzumab, and immunotherapy are not safe during pregnancy due to fetal risks.
• A multidisciplinary team should create an individualized plan; pregnancy termination is not automatically required.

Why This Research Matters: Breast Cancer During Pregnancy

Breast cancer (BC) is the most common cancer in women worldwide, and approximately 7% of cases are diagnosed before the age of 40. While cancer diagnosed during pregnancy is rare — occurring in about 1 case per 1,000 deliveries — breast cancer is actually the most common cancer to affect pregnancy.

The incidence of breast cancer during pregnancy has been increasing in recent years. Among pregnant women under age 45, the rate of breast cancer ranges from 2.6% to 6.9%. For women under 35, breast cancer accounts for 15.6% of all breast cancer cases in that age group.

Breast cancer diagnosed during pregnancy presents a complex challenge for both the patient and her clinicians. The expectation is that pregnant patients should be treated as effectively as non-pregnant patients, but standard therapies must be modified to balance the benefit to the mother against the risk to the fetus. The authors of this review stress that a multidisciplinary team (MDT) approach at specialized centers is crucial. This team typically includes breast surgeons, obstetricians, radiologists, pathologists, and anesthesiologists who work together to make an early diagnosis and comprehensively evaluate patients at different stages of pregnancy and different stages of breast cancer.

The purpose of this article is to highlight the special considerations that must be addressed before treating pregnant women with breast cancer, and to review the existing evidence for managing these patients safely and effectively.

Understanding the Biology of Pregnancy-Related Breast Cancer

Although the clinical features of breast cancer in pregnant women are similar to those in non-pregnant women, the diagnosis may be delayed. This happens because normal pregnancy-related changes — such as breast enlargement, colostrum secretion, and other physiological alterations — can mask or mimic the signs of cancer. It is important to understand that pregnancy does not cause breast cancer; rather, cancer can develop coincidentally during pregnancy.

However, pregnancy can have a profound effect on the biology of breast cancer. Most breast cancers that develop during pregnancy are invasive ductal carcinoma (cancer that begins in the milk ducts and spreads to surrounding breast tissue). Invasive lobular carcinoma (cancer that begins in the milk-producing glands) develops far less frequently during pregnancy.

Studies have reported that triple-negative breast cancer (TNBC) — a more aggressive subtype that lacks estrogen receptors, progesterone receptors, and HER2 protein — is more prevalent during pregnancy. Compared to sporadic breast cancer (cancer that occurs outside of pregnancy), pregnancy-associated breast cancer tends to have:

• A higher histologic grade (more abnormal-looking cells)
• A more aggressive profile
• A more advanced stage at the time of diagnosis
• A larger tumor size
• A higher frequency of lymph node involvement
• Less frequent expression of estrogen receptors (ERs) and progesterone receptors (PRs)
• A greater likelihood of being inflammatory breast cancer

The ultimate prognosis for breast cancer during pregnancy is a subject of debate. Some studies have found no significant differences in prognosis between pregnant and non-pregnant women with breast cancer. However, a recent meta-analysis (a statistical analysis combining the results of multiple studies) noted a poorer prognosis for breast cancer in pregnant women.

Pregnancy may also alter gene expression patterns in breast cancer cells. Researchers have observed abnormal expression of several genes involved in cancer development, including:

• Oncogenes (cancer-promoting genes): MYC, SRC, and FOS
• Tumor suppressor genes (genes that normally prevent cancer): TP53, PTEN, and CAV1
• Apoptosis regulators (genes controlling programmed cell death): PDCD4, BCL2, and BIRC5
• Transcription regulators (genes controlling how other genes are turned on/off): JUN, KLF1, and SP110
• DNA repair genes: Sig20, BRCA1, BRCA2, and FEN1
• Cell proliferation genes: AURKA and MKI67
• Immune response genes: PD1 and PDL1

These genetic differences help explain why pregnancy-associated breast cancer can behave differently and may require a tailored treatment approach.

How Breast Cancer Is Diagnosed and Staged During Pregnancy

One of the most critical issues is delayed diagnosis. During pregnancy, breast cancer diagnosis is often delayed by 1 to 13 months due to breast enlargement, colostrum secretion, and other pregnancy-related changes that can hide a suspicious mass. While 80% of palpable breast masses (masses that can be felt) found during pregnancy are benign, any mass that persists for more than 2 weeks should be taken seriously and evaluated.

The evaluation of a suspicious breast mass proceeds similarly whether a woman is pregnant or not, but the standard staging workup must prioritize fetal safety. Here is what the review recommends at each step:

Imaging: What Is Safe and What Should Be Avoided?

Breast ultrasonography (ultrasound) should be the first imaging test used to assess a breast mass during pregnancy because it is safe and highly sensitive. However, ultrasound may be less sensitive during pregnancy because breast tissue becomes denser.

Mammography with appropriate abdominal shielding can be useful to evaluate the extent of the disease. The abdominal shield protects the fetus from radiation exposure.

Magnetic resonance imaging (MRI) without gadolinium contrast can be used for further evaluation. Gadolinium (the contrast dye used in MRI) can cross the placental barrier and is considered potentially teratogenic (capable of causing birth defects), so it must be avoided during pregnancy.

Tests to avoid during pregnancy include:

• Bone scans and positron emission tomography (PET) — The ESMO (European Society for Medical Oncology) guidelines state these should be avoided during pregnancy
• Contrast-enhanced CT scans — should be avoided
• PET/MRI — Although a few studies suggest 18F-FDG PET and PET/MRI involve low fetal radiation exposure, there is not enough evidence to support their use for breast cancer staging during pregnancy

A radiologist must be a key member of the medical team to calculate the total radiation dose, review the indications for each test, and assess the risk-benefit ratio.

Biopsy: How Tissue Samples Are Taken

A core needle biopsy performed under local anesthesia is the preferred method for sampling any clinically suspicious breast mass during pregnancy. This involves using a hollow needle to remove a small cylinder of tissue for examination under a microscope.

Suspected metastatic lymph nodes (lymph nodes that may have cancer spread to them) should be evaluated with ultrasound and fine needle aspiration biopsy for confirmation.

An important detail: pathologists should be informed that the patient is pregnant. This is because the presence of hyperplastic cells (cells that multiply excessively) during pregnancy can simulate atypia (abnormal cells), leading to an increase in false-positive results — meaning a biopsy might appear abnormal when it is actually benign.

Systemic staging studies (tests to determine if cancer has spread) are recommended for advanced cancers, but only if the results would change treatment options. If necessary, staging tests should include chest radiography with abdominal shielding, liver ultrasound, and/or non-contrast skeletal MRI.

Monitoring the Health of Both Mother and Baby

Pregnant women with breast cancer should always be considered a high-risk group. This means they need more careful and continuous monitoring throughout their pregnancy, including:

• Morphometric ultrasonography — detailed ultrasound measurements of the fetus's growth and development
• Umbilical artery Doppler assessment — a test that measures blood flow through the umbilical cord to check how well the placenta is delivering oxygen and nutrients to the baby

Calculating the gestational age (how far along the pregnancy is) and the expected date of delivery is critically important, as these factors directly impact breast cancer treatment planning. Allowing the pregnancy to reach full term (37 weeks) is strongly recommended whenever possible.

The gynecologist/obstetrician should be part of the multidisciplinary team and will determine the mode of delivery (vaginal delivery or cesarean section) based on obstetric indications — meaning decisions about how the baby is delivered are made for pregnancy-related reasons, not cancer-related reasons.

Possible micrometastases in the placenta (tiny clusters of cancer cells that may have traveled to the placenta) should be examined after delivery.

To avoid hematological toxicity (dangerously low blood cell counts) in the mother and fetus, the last round of chemotherapy should be administered 3 weeks prior to the planned date of delivery.

There is encouraging news for patients. Mounting evidence shows that breast cancer treatment during pregnancy has no clear adverse effects on growth, cognitive function, or cardiac function in early childhood. This suggests that a diagnosis of cancer during pregnancy should not be an automatic indication to abort the pregnancy. The only factor associated with a worse cognitive outcome in children was prematurity — and this was independent of whether the mother received cancer treatment.

Understanding the Risks of Anesthesia

If surgery is needed during pregnancy, anesthesia safety for both mother and fetus is a major consideration. Pregnancy causes significant changes in a woman's anatomy and physiology that increase the potential hazards of anesthesia. These maternal changes include:

• Increased cardiac output (the amount of blood the heart pumps)
• Reduced functional residual capacity (the amount of air remaining in the lungs after a normal breath out)
• Dilation of the pyelocaliceal system (widening of the drainage system of the kidneys)
• Dilutional anemia (a decrease in red blood cell concentration due to increased blood volume)
• Gastroesophageal reflux (stomach acid flowing backward into the esophagus)
• Changes in glucose and adrenal metabolism

The main anesthesia-related risks during pregnancy involve airway edema (swelling of the airway tissues), restrictive lung physiology (reduced ability of the lungs to expand fully), and aspiration (inhaling stomach contents into the lungs).

A previous study suggested that adverse fetal outcomes after surgery during pregnancy may be related to the mother's underlying medical condition rather than the effects of anesthesia itself — a reassuring finding.

For patient safety, the review notes that the patient should be positioned with a 15–30° left lateral tilt during surgery. This position reduces aortocaval compression (pressure on the major blood vessels) and decreases the incidence of supine hypotensive syndrome (a dangerous drop in blood pressure when lying flat on the back).

Treatment Options During Pregnancy: An Overview

Guidelines state that breast cancer during pregnancy should be treated in accordance with the management of breast tumors in non-pregnant women, including local control of the disease and prevention of systemic (whole-body) metastases. However, several important factors must be considered before treatment begins:

• Clinicopathological characteristics (the specific features of the tumor)
• Gestational age at the time of breast cancer diagnosis
• Expected date of delivery
• The patient's own wishes

The goals of the multidisciplinary team are three-fold: to cure the pregnant patient of breast cancer, to support the pregnancy, and to not harm the fetus.

Surgery During Pregnancy

Surgery can be considered safe in all trimesters of pregnancy. The gestational age at diagnosis is an important factor in devising the surgical plan. Two main surgical options are available:

• Radical modified mastectomy (RMM) — removal of the entire breast along with some of the underarm lymph nodes
• Breast-conserving surgery (also called lumpectomy) — removal of only the tumor and a small margin of surrounding healthy tissue

Both are reasonable options for a pregnant woman with breast cancer, with some important caveats:

In the first trimester: If breast-conserving surgery is chosen, the radiation therapy that normally follows it may need to be delayed for the sake of fetal safety. Therefore, mastectomy should be recommended for patients who wish to continue the pregnancy — removing the whole breast eliminates the need for follow-up radiation.

In the second and third trimesters: Breast-conserving surgery might be an option for early-stage breast cancer.

Reconstructive surgery (surgery to rebuild the breast shape) should be postponed until after birth. This is because normal pregnancy-related breast changes could affect the cosmetic results in unexpected ways.

Regarding sentinel lymph node biopsy (a procedure to remove and examine the first lymph node that cancer would likely spread to): breast cancer during pregnancy has a high incidence of axillary lymph node metastases (cancer spread to underarm lymph nodes). However, there is no level 1 evidence (the highest grade of evidence from randomized controlled trials) to support the routine use of sentinel lymph node biopsy in pregnant breast cancer patients. The American Society of Clinical Oncology (ASCO) guidelines do not support this procedure during pregnancy, while the National Comprehensive Cancer Network (NCCN) guidelines endorse its safety according to the patient's wishes. Other guidelines advise sentinel lymph node biopsy when axillary ultrasound and a suspicious lymph node biopsy are negative.

When sentinel lymph node biopsy is performed, it should be done using 99mTc-albumin nanocolloids (a radioactive tracer that is considered safe). The following dyes should be avoided:

• Blue dye and isosulfan blue — avoided due to the risk of an allergic or anaphylactic (severe allergic) reaction in the mother
• Methylene blue — contraindicated during the first trimester because it is teratogenic (can cause birth defects)

Systemic Treatments: Chemotherapy, Targeted Therapy, and More

Systemic treatments — including chemotherapy, hormone therapy, targeted therapies, and immunotherapy — are generally avoided in the first trimester because of the high risk of teratogenicity (birth defects) and abortion. Available data on the risks of these drugs during pregnancy are limited to case reports, animal studies, and studies with small sample sizes.

Before any oncological (cancer) treatment is given, a fetal ultrasound must be performed to rule out pre-existing abnormalities. Major factors that must be evaluated before starting systemic therapy include:

• Physiologic changes during pregnancy
• Gestational age
• Placental passage (how easily the drug crosses the placenta to reach the fetus)
• Pharmacokinetic characteristics of the drug (how the body absorbs, distributes, metabolizes, and eliminates it)

Chemotherapy: The Safest Options

Anthracyclines are considered the treatment of choice during pregnancy because of their very low placental transfer. One study reported that doxorubicin and epirubicin are not teratogenic (do not cause birth defects), while another study found they may increase the risk of prematurity and low birth weight.

Multiple chemotherapy regimens have been studied in pregnancy, including:

• FAC — 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide, given in 3-week cycles
• FEC — 5-fluorouracil, epirubicin, and cyclophosphamide
• AC — doxorubicin (Adriamycin) and cyclophosphamide
• EC — epirubicin and cyclophosphamide
• Weekly epirubicin as a single drug

The AC and EC regimens are the ones most often used to treat breast cancer during pregnancy. A retrospective cohort study (a study that looks back at existing patient data) indicated that dose-dense chemotherapy — giving chemotherapy more frequently than standard schedules — was safe in 10 pregnant women with breast cancer. However, the review notes that a dose-dense schedule may generally not be recommended during pregnancy.

Although chemotherapy is considered safe and well-tolerated during the second and third trimesters, the multidisciplinary team must closely monitor fetal safety and maternal blood pressure throughout treatment. Importantly, chemotherapy should not be administered after 35 weeks of gestation to prevent hematological complications (blood-related complications) during delivery.

Targeted Therapies: What Is Contraindicated

Trastuzumab (Herceptin) is strictly contraindicated throughout pregnancy due to the high risk of oligohydramnios (low amniotic fluid) and/or anhydramnios (no amniotic fluid). The erbB2/neu gene, which this drug targets, is related to fetal organogenesis (the development of fetal organs). A systematic review and meta-analysis concluded that more adverse events occur when trastuzumab is used in the second/third trimester than in the first trimester.

Pertuzumab and T-DM1 (ado-trastuzumab emtansine) are also contraindicated because no data are available on their use in pregnant women.

Lapatinib (a small-molecule tyrosine kinase inhibitor) is presumed to cross the placenta during all phases of pregnancy. The limited data available do not support its use in pregnant patients.

CDK4 and CDK6 inhibitors (a class of targeted drugs used in breast cancer) have no available data on use during pregnancy.

Hormone (Endocrine) Therapy: Not Safe During Pregnancy

Endocrine therapy — including tamoxifen and luteinizing hormone-releasing hormone (LHRH) analogues — is contraindicated for treating breast cancer during pregnancy due to the high risk of birth defects, which can be up to 17.6%.

Tamoxifen is teratogenic and increases the risk of breast cancer in offspring, as verified in animal experiments. A systematic review identified major malformations associated with tamoxifen exposure during pregnancy, including:

• Ambiguous genitalia (genitals that are not clearly male or female)
• Pierre Robin sequence (a condition marked by an underdeveloped jaw, a cleft palate, and a tongue that falls backward)
• Oculoauriculovertebral dysplasia (also called Goldenhar syndrome, affecting the face, ears, and spine)

Minor malformations include preauricular skin tags (small skin growths in front of the ear) and severe hypermetropia (severe farsightedness).

Aromatase inhibitors — another class of hormone therapy — have no available data on human exposure during pregnancy, though data from animal models exist.

Radiation Therapy: Timing Is Everything

Radiation has dose- and gestational-week-dependent effects on the fetus. Due to its teratogenic effects, radiation therapy is generally not considered a safe treatment option during pregnancy. However, radiotherapy could be performed in the first trimester and at the beginning of the second trimester with careful dose adjustment — an exposure of 0.01 mGy (milligray, a unit of radiation absorption) is below the threshold dose — and with proper abdominal shielding. The multidisciplinary team must carefully balance the risks and benefits of radiation therapy for both the mother and the fetus.

Immunotherapy: Not Recommended

The PD-1/PD-L1 pathway — the target of many modern immunotherapy drugs — is involved in immune tolerance during pregnancy (the process that prevents the mother's immune system from rejecting the fetus). In studies involving pregnant animals, anti-PD-1/PD-L1 treatment increased the risk of miscarriages, premature delivery, and birth mortality. Therefore, immunotherapy during pregnancy is contraindicated.

What This Means for Patients

For a woman diagnosed with breast cancer during pregnancy, the review offers several important takeaways:

• A cancer diagnosis should not automatically mean termination of pregnancy. Evidence shows that treatment can be safe for the baby, especially when chemotherapy is given in the second and third trimesters.
• It takes a village. The multidisciplinary team approach is not optional — it is essential. Patients should expect to see multiple specialists who work together to plan their care.
• Timing matters. The gestational age at diagnosis drives many treatment decisions. Knowing the expected date of delivery is as important as knowing the cancer stage.
• Not all treatments are equal in pregnancy. Some chemotherapy drugs (like anthracyclines) have decades of safety data in pregnancy, while other treatments (like trastuzumab, tamoxifen, and immunotherapy) are strictly contraindicated.
• Early diagnosis saves lives and reduces complications. Because pregnancy can mask breast symptoms, patients should not ignore a persistent breast mass. A mass lasting more than 2 weeks should be evaluated with ultrasound.

What This Review Could Not Answer

The authors acknowledge significant gaps in evidence. Clinical trials for breast cancer treatments routinely exclude pregnant women, which means much of the available data comes from case reports, animal studies, and small retrospective reviews rather than large randomized controlled trials.

Specific unanswered questions include:

• The safety of dose-dense chemotherapy during pregnancy (only one small study of 10 women exists)
• The safety of newer targeted therapies such as pertuzumab, T-DM1, lapatinib, and CDK4/6 inhibitors
• The effects of aromatase inhibitors during pregnancy (no human data available)
• Whether the poorer prognosis seen in pregnancy-associated breast cancer is due to the cancer biology itself or the inevitable delays in diagnosis

The long-term outcomes for children exposed to cancer treatment in the womb — particularly cardiac function, fertility, and cancer risk later in life — require more research, though current evidence on growth, cognition, and cardiac health in early childhood is reassuring.

Recommendations for Patients and Families

Based on this review, here is what patients should know and consider:

1. Seek care at a specialized center. Management of breast cancer during pregnancy should be handled by a multidisciplinary team with experience in this complex situation. Ask if your hospital has a team that includes breast surgeons, obstetricians, radiologists, pathologists, and anesthesiologists who work together regularly.
2. Report any persistent breast mass immediately. Do not assume a lump is just a normal pregnancy change. While 80% of breast masses during pregnancy are benign, a mass lasting more than 2 weeks deserves proper evaluation.
3. Discuss all treatment options with your team before deciding. Ask about the specific chemotherapy regimens recommended, the gestational age windows for safe treatment, and why certain medications (like hormonal therapy or HER2-targeted drugs) are not recommended during pregnancy.
4. Plan the delivery timeline carefully. Your team should help you coordinate the timing of chemotherapy so that the last dose is given at least 3 weeks before the planned delivery date, and chemotherapy should not be given after 35 weeks of gestation.
5. Allow the pregnancy to reach full term if possible. Full term (37 weeks) is strongly recommended. The only factor linked to worse cognitive outcomes in children was prematurity, not cancer treatment itself.
6. Ask about fetal monitoring. Your pregnancy should be monitored as a high-risk pregnancy, with regular ultrasounds and umbilical artery Doppler assessments.
7. Know that abortion is not the only option. The evidence does not support automatic termination of pregnancy. Many women can successfully complete cancer treatment while continuing their pregnancy, giving birth to healthy babies.
8. Plan for breast reconstruction after delivery. Reconstructive surgery should wait until after birth for the best cosmetic outcomes.

Frequently Asked Questions

Why is breast cancer diagnosis often delayed during pregnancy?

Normal pregnancy changes like breast enlargement, colostrum secretion, and denser tissue can hide a suspicious lump. This can delay diagnosis by 1 to 13 months. While 80% of breast masses during pregnancy are benign, any lump lasting more than 2 weeks should be evaluated with ultrasound.

Is surgery safe during pregnancy for breast cancer?

Yes, surgery for breast cancer is considered safe in all trimesters of pregnancy. Mastectomy or breast-conserving surgery may be options depending on your stage and gestational age. Reconstructive surgery should be postponed until after birth to allow breast changes from pregnancy to settle.

Which breast cancer treatments are not safe during pregnancy?

Hormone therapy like tamoxifen is contraindicated because it risks birth defects. HER2-targeted drugs such as trastuzumab, pertuzumab, and T-DM1 are also unsafe. Immunotherapy is not recommended. Radiation therapy is generally avoided. Your medical team will help choose safe options for your situation.

When can chemotherapy be given during breast cancer treatment in pregnancy?

Chemotherapy is generally avoided in the first trimester due to birth defect risk. It can be given in the second and third trimesters. Anthracycline-based regimens like AC or EC are often used. The last dose should be at least 3 weeks before delivery, and not after 35 weeks of gestation.

Do I have to terminate my pregnancy if I have breast cancer?

No. Evidence shows that treatment can be safe for the baby, especially when chemotherapy is given in the second and third trimesters. The review states that cancer during pregnancy should not be an automatic reason for abortion. Many women continue pregnancy and deliver healthy babies.

How is the baby monitored during breast cancer treatment?

Your pregnancy is considered high-risk. Monitoring includes detailed ultrasound measurements of fetal growth, umbilical artery Doppler assessment to check blood flow, and careful tracking of gestational age. The team aims for delivery at full term, 37 weeks, whenever possible. The last chemotherapy is timed to protect the baby.

Source Information

Original article title: Breast cancer and pregnancy- Why special considerations prior to treatment are needed in multidisciplinary care

Authors: Mingdi Zhang, Jing Zhou, Ling Wang

Affiliations: Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; Laboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China; The Academy of Integrative Medicine of Fudan University, Shanghai, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China

Journal: BioScience Trends, 2021; 15(5):276-282. DOI: 10.5582/bst.2021.01187

Article type: Review

Funding: The original research was supported by grants from the Shanghai Municipal Commission of Health, the Obstetrics and Gynecology Hospital of Fudan University, the Shanghai Municipal Commission for Science and Technology, the Shanghai Natural Science Fund, and the Chinese Association of Integration of Traditional and Western Medicine.

Conflicts of interest: The authors declared no conflicts of interest.

Note: This patient-friendly article is based on peer-reviewed research published in BioScience Trends. It is intended for educational purposes and should not replace individualized medical advice from your healthcare team. Always discuss your specific situation with your doctors.