Breast cancer, the most common malignancy in women, frequently develops during the premenopausal years. The great majority of these breast cancers can be successfully treated, and the decision to have children remains a real and important consideration. The relationship between breast cancer and a subsequent pregnancy is complex, and decisions regarding one may ultimately affect the course or outcome of the other.
Collichio et al review the major clinical parameters involved in this relationship. As this review suggests, the interdependence of a breast cancer and subsequent pregnancy gives rise to three important questions in clinical practice:
1) How does contemplation of a future pregnancy influence the decisions about selection of therapy for a current (untreated) breast cancer?
2) How does therapy and prognosis for a previously treated breast cancer affect the decision to have a subsequent pregnancy?
3) How does a pregnancy alter the course and management of a previously diagnosed breast cancer?
This excellent review provides important information that may aid the clinician and patient in making decisions about these issues.
Future Pregnancy and Selection of Breast Cancer Therapy
Breast cancer is commonly treated with combined-modality therapy, which may include surgery, radiation therapy, chemotherapy, and antiestrogen therapy. As the authors discuss, each of these treatments may influence, either directly or indirectly, a subsequent pregnancy. The authors also recommend that many of these issues (regarding pregnancy) should be addressed while patients are considering their choice of therapy.
For certain of these modalities, choices are availablemastectomy vs axillary dissection/breast-sparing radiotherapy, preoperative vs postoperative chemotherapy, or choice of chemotherapy agents and dose intensity. In addition, for high-risk women, especially those who are BRCA1- or BRCA2-positive, contralateral prophylactic mastectomy may be considered. These difficult decisions are further complicated by the uncertainty over prognosis.
The degree to which concerns over a future pregnancy should influence these decisions is unclear. It is appropriate for the clinician to discuss with the patient the potential adverse effects of therapy on her ability to conceive or carry a pregnancy. Selection of the most effective treatment of the malignancy, however, is paramount, and should govern any medical decision.
Impact of Therapy and Prognosis on Decisions About Pregnancy
A point made in the review that warrants emphasis is the importance of the prognosis of the breast cancer on decisions to have children and the timing of the pregnancy. Survival time and the potential to raise children to adults should be discussed.
Prognosis clearly varies according to stage, and the recommendations for family planning for women with stage I breast cancer may differ from those for women with four or more positive axillary nodes or locally advanced breast cancer, as the latter groups are at significant risk for systemic failure even after 5 years. For women who are BRCA1-positive, who are at increased risk for contralateral breast cancer and ovarian cancer and whose children have a 50% chance of inheriting the gene, genetic counseling might be considered. Although the effects of (previously administered) conventional chemotherapy on a pregnancy and the fetus appear to be minimal, the effects of dose-intensive chemotherapy or experimental regimens are largely unknown.
An important consideration regarding pregnancy following breast cancer is monitoring for recurrence and potential interruption of adjuvant therapy. The multiple signs and symptoms that occur during pregnancy may make detection of recurrence difficult and limit the nature of tests performed, especially for in-breast recurrence. In addition, the consequences of a 9-month interruption of adjuvant tamoxifen(Drug information on tamoxifen) (Novaldex) therapy, which presumably would be necessary during the first 5 years, is unknown. For these reasons and those discussed above (regarding prognosis), it is perhaps appropriate to defer pregnancy until adjuvant therapy has been completed and the risk of recurrence is low.
Effects of Pregnancy on Breast Cancer
On the one hand, it is well known that age of first pregnancy can influence the risk of developing a new breast cancer, having an adverse effect if pregnancy occurs after age 35. As Collichio et al demonstrate, for reasons that are not fully understood, a pregnancy has no deleterious effect and may, in fact, have a beneficial effect on survival from a previously treated breast cancer. This benefit is independent of stage, axillary lymph node status, number of pregnancies, and management of the pregnancy.
The authors suggest that the improvement in survival may be attributable to patient selection, immune tolerance, or a superphysiologic state of estrogen activity during pregnancy. Approximately 55% to 60% of breast cancers in premenopausal women are estrogen receptor (ER)-positive and thus hormonally responsive. Interestingly, the BRCA1 gene, which has tumor-suppressor functions, appears to be regulated, in part, by estrogen. In ER-positive human breast cancer cells, estradiol(Drug information on estradiol) stimulates and antiestrogens inhibit BRCA1 expression. In sporadic breast cancer, where BRCA1 mutations are rare, these findings may provide an additional explanation for the lack of adverse effects of pregnancy on survival from a previous breast cancer.
Collichio et al provide an important review aimed at clarifying the complex relationship between a breast cancer and subsequent pregnancy. As our understanding of breast cancer and its management continues to improve, sub- sequent family planning will become even more important. Prospective studies addressing epidemiologic, psychosocial, and molecular issues are needed, and should provide further answers to these questions, which will benefit both the patient and her children.