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 (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 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.
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Breast Carcinoma: Risk and Detection, pp 30-50. Philadelphia, WB
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4. Spillman MA, Bowcock AM: BRCA1 and BRCA2 mRNA levels are
coordinately elevated in human breast cancer cells in response to
estrogen. Oncogene 13:1639-45,1996.