Commentary (Overmoyer): Breast Cancer During Pregnancy

The article authored by Drs. Gwyn and Theriault is a timely and thorough review of the difficulties surrounding the treatment of breast cancer during pregnancy. The timeliness of the article relates to the current trend of delaying pregnancy until an age at which the incidence of breast cancer becomes a reality, not just a possibility. The authors present a comprehensive discussion of the problems associated with delays in diagnosing breast cancer during pregnancy. They describe ways to increase early diagnosis in this cohort of patients, including endorsing a heightened awareness of the disease among obstetricians, increasing the use of safe diagnostic imaging techniques such as ultrasound and breast magnetic resonance imaging (MRI), and allaying fears of the rare complications associated with breast-tissue sampling during pregnancy.

Staging and the Multidisciplinary Approach to Treatment

The remainder of the article deals with approaches to treatment. The discussion on appropriate staging is thorough and focuses on the safety of the fetus, and the calculated risk of identifying metastasis in the patient newly diagnosed with breast cancer. It should be pointed out that complete staging with computed tomography (CT) scans of the chest, abdomen, pelvis, and bone may also be useful immediately after delivery, because metastatic disease may still be detected after treatment in patients presenting locally with high-risk breast cancer.

Information gained from a maternal echocardiogram could be instrumental in determining the ability of the patient to carry the fetus to term and estimating the risk of cardiac compromise caused by chemotherapy. Informing a patient of the rarity of transmitting breast cancer directly to the fetus is important in alleviating anxiety. However, metastasis to the placenta is not a rare occurrence, and that fact should be explained to the maternal patient since this phenomenon is not currently associated with a poor prognosis for mother or fetus.[1]

Drs. Gwyn and Theriault support the involvement of a team of expert physicians early in the diagnosis to facilitate accurate determination of fetal age and to plan the optimal course of safe therapy. The delivery of the baby must be timed carefully to avoid the complications associated with proximate chemotherapy administration. If these two events occur too closely, the result may be incomplete metabolism of the chemotherapy by the fetal circulation during the change from maternal to fetal circulation, and the development of significant fetal cytopenias.[2] Vigilant assessment of fetal lung maturation is necessary to plan the optimal time for inducing labor, and to assist the oncologist in scheduling administration of chemotherapy.

Systemic Disease Treatment

An important contribution of the article is in highlighting the paucity of data available on this particular clinical situation. The majority of data published on the safety of administering chemotherapy during pregnancy involves the treatment of leukemia and lymphoma, which is more prevalent in this age group.[3] Consequently, there are data supporting the safety of using anthracyclines, vinca alkaloids, and alkylating agents during the second and third trimester of pregnancy.[2]

Drs. Gwyn and Theriault specifically recommend that chemotherapy be avoided during the first trimester, and that antimetabolites and tamoxifen (Nolvadex) be avoided during the entire pregnancy. Fortunately, using the AC combination regimen (doxorubicin [Adriamycin]/cyclophosphamide [Cytoxan, Neosar]) for 12 weeks is comparable in efficacy to 6 months of CMF (cyclophosphamide/methotrexate/fluorouracil). The shorter duration of AC use makes it safer in the treatment of the pregnant breast cancer patient. Standard doses of AC should be adequate, since this combination is not influenced by distribution into a third space (ie, ascites, pleura, or amniotic fluid).

The safety of the taxanes in this setting is unknown, although there are data that demonstrate a very safe profile for the vinca alkaloids, and this may also pertain to the taxanes.[2] The literature is even scarcer on the use of cytokines and antiemetics during pregnancy, but case reports support the safety of such agents.[4]

Local Disease Treatment

Knowledge of fetal maturity also has an impact on the choice of surgical treatment for breast cancer. Depending on fetal age, breast conservation may be a therapeutic option when definitive radiation can be delayed until after delivery, and after adjuvant chemotherapy is completed.[5] Drs. Gwyn and Theriault suggest mastectomy or breast-conservation therapy in the setting of pregnancy. They appropriately conclude that mastectomy may be a more frequent treatment choice due to its low surgical risk and associated need to delay the initiation of systemic treatment for 4 to 6 weeks postoperatively-thus allowing for fetal maturation into the second trimester.

Conclusions

The article by Drs. Gwyn and Theriault presents a concise review of the limited data available on the treatment and outcome of breast cancer diagnosed during pregnancy. The authors conclude that in the majority of circumstances, termination of pregnancy is not necessary in order to offer optimal treatment to the breast cancer patient.

Breast cancer during pregnancy does not appear to be associated with a poorer prognosis than is comparably staged breast cancer. Therefore, regardless of the psychological burden of diagnosing cancer in a pregnant patient, one can be cautiously optimistic that the diagnosis can be made early, and that systemic therapy can be administered without detriment to the fetus.

One strategy for overcoming the limited exposure of clinicians to this problem and facilitating a more complete database might be to create a national registry of pregnant breast cancer patients including treatment regimens and outcomes. In this way, we can gather enough evidence-based data to make confident recommendations on the ideal treatment of breast cancer during pregnancy.

References:

1. Potter JF, Schoeneman M: Metastasis of maternal cancer to theplacenta and fetus. Cancer 25:380-388, 1970.

2. Doll DC, Ringenberg QS, Yarbro JW: Antineoplastic agents andpregnancy. Semin Oncol 16:337-346, 1989.

3. Garber JE: Long-term follow-up of children exposed in uteroto antineoplastic agents. Semin Oncol 16:437-444, 1989.

4. Arango HA, Kalter CS, Decesare SL, et al: Management ofchemotherapy in a pregnancy complicated by a large neuroblastoma. Obstet Gynecol84:665-668, 1994.

5. Mayr NA, Wen B, Saw CB: Radiation therapy during pregnancy.Obstet Gynecol Clin North Am 25:301-321, 1998.