Treatment of Breast Cancer During Pregnancy?

Harold J. Burstein, MD, PhD

Disclosures

July 19, 2001

Question

My 32-year-old patient tested positive for breast cancer in 6 nodes. She's 15 weeks pregnant, but refuses a therapeutic abortion. What would you recommend?

Response from Harold J. Burstein, MD, PhD

Perhaps no aspect of breast cancer care is more challenging than the treatment of the pregnant patient. In addition to the usual complexities of treatment decisions, one must add the incalculable factors related to the importance of childbearing, and the potential for side effects upon the fetus or child through exposure to chemotherapy. It is very difficult to make general comments about treating such patients.[1,2] Each individual will weigh the potential risks and benefits differently, and may reach different decisions. Patients are invariably best served by multimodality team approaches, with coordinated efforts of surgeons, medical oncologists, and obstetricians trained in high-risk maternal-fetal medicine.

The case under discussion involves a pregnant patient with breast cancer, metastatic to multiple lymph nodes. Routine treatment recommendations in the absence of pregnancy would call for definitive surgery, radiation therapy, adjuvant chemotherapy, and, if the tumor is hormone-receptor positive, tamoxifen. To what extent should these recommendations differ in the pregnant patient? Ultimately, the patient should be advised to have similar treatments, although the specific timing of various therapies may be affected by her concurrent pregnancy.

There are very few reports of the treatment of women with breast cancer during pregnancy. None suggest that therapeutic abortion improves the outcome for such women. The largest series of patients contain 20 and 24 patients, respectively,[3,4] and lack long-term follow-up data on the offspring born following chemotherapy exposure. Thus, it must be acknowledged that the side effects of chemotherapy treatment during pregnancy on the pregnancy itself and on the children are not well characterized.

The best data for management of breast cancer during pregnancy come from the experience at the MD Anderson Cancer Center in Houston, Texas, in which 24 women were treated over an 8-year span using a standardized protocol.[4] After surgery (ie, modified radical mastectomy), patients received adjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) until the time of delivery. There were no unexpected antepartum complications; 12% had preterm labor, and 4% had pre-eclampsia. Postpartum lactation was impaired in all patients, and patients were advised not to breast feed on account of chemotherapy exposure. None of the 24 children had congenital abnormalities; 23 of the 24 had birth weights above the 10th percentile. No unusual neonatal complications were noted, although 1 baby had transient leukopenia.

The standardized MD Anderson Cancer Center treatment program called for the following evaluations and/or treatments:

Metastatic work up including 2-view chest x-ray with abdominal shielding and abdominal/pelvic ultrasound or magnetic resonance imaging;

Assessment of blood counts and renal and liver functions;

Genetic counseling to discuss potential effects of chemotherapy on fetus;

Surgical consultation, with modified radical mastectomy recommended for women with operable breast cancer;

Informed consent using a specialized consent document;

Chemotherapy treatment with FAC every 3 to 4 weeks during the second and third trimesters;

Use of ondansetron, promethazine, or prochlorperazine as an antiemetic;

High-risk obstetrical care including serial fetal ultrasound evaluations at least every 3 to 4 weeks; and

Fetal nonstress biophysical profiles between 28 weeks gestation and term

Treatment with chemotherapy during the first trimester is contraindicated, as studies show high rates of fetal side effects. Treatment with tamoxifen or therapeutic radiation therapy is also contraindicated during pregnancy. Women requiring tamoxifen or radiotherapy were treated after delivery.

This treatment experience can be used to guide the active care of women receiving adjuvant chemotherapy during pregnancy. In the case of women with inoperable breast cancer, chemotherapy treatment at MD Anderson Cancer Center was begun prior to surgery. For women diagnosed with breast cancer close to the end of pregnancy, postsurgical treatment can often be reasonably deferred until after delivery.

Their positive experience suggests that this approach to breast cancer is feasible. Other data are available from a French national survey of the treatment of women with breast cancer during pregnancy.[3] Twenty women who received chemotherapy during pregnancy were reviewed retrospectively. Two patients who received chemotherapy in the first trimester had spontaneous abortions, and 1 pregnancy treated in the second trimester had intrauterine death. Of the 17 remaining live births, 2 infants had cytopenias related to chemotherapy exposure, and 1 had had fetal growth retardation. One newborn died in its second week without obvious explanation. This smaller study of a more heterogeneous patient population highlights the problem of being too confident that chemotherapy during pregnancy is safe.

It is hard to overestimate the uncertainties and challenges of managing patients such as the one presented in this case. Ultimately, physicians and patients must acknowledge the potential risks and the potential benefits, and work together to make the best treatment decisions for each individual.

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