Pregnancy After Breast Cancer: From Psychosocial Issues Through Conception

Since physicians have stressed complete rehabilitation after breast cancer treatment, including breast reconstruction and psychosocial aspects, it follows that young women who have undergone such treatment may wish to resume their life roles, which often include motherhood. Consequently, the issue of pregnancy after breast cancer treatment has assumed paramount importance. This pertinent, accurate review of such a complex issue can be so brief because there are so few data on the subject. Given the diversity of the issues presented in the review, it is helpful to consider them individually.

Sexual Function
After discussing the lack of difference in sexual functioning between women who have undergone breast conservation and those who have had a mastectomy, the authors complete their discussion by stating that “weight gain, fatigue, or change in the appearance of the hair may decrease sexual desire or performance.” Nevertheless, they do not mention possibly the most important cause of sexual dysfunction in these women: premature menopause brought on by chemotherapy. Even among women who have no desire to bear children, sexual functioning and quality of life are compromised by premature menopause, with its attendant symptoms of hot flashes, sleep disturbance, decreased libido, and vaginal dryness.

Many studies have reported on such long-term complications of chemotherapy as therapy-related leukemia and cardiomyopathy, but there are virtually no data and no prospective studies on iatrogenic menopause.[1] Since the improved survival following chemotherapy appears to be independent of menopause induction,[2] ovarian toxicity should be evaluated in the risk-benefit assessment of chemotherapy.

Little is known about the determinants of premature menopause in this population, and even less is known about the impact of premature menopause on quality of life. Along with UT M. D. Anderson Cancer Center and Wake Forest University School of Medicine, our group at Memorial Sloan-Kettering Cancer Center is beginning a long-term prospective study, funded by the US Army Breast Cancer Research Program (grant number DAMD 17-96-1-6292), that will follow 800 breast cancer patients, age 18 to 44 years, from diagnosis onward. The study participants will complete menstrual bleeding diaries and complete questionnaires on their quality of life, especially as it relates to the menopausal state.

Infertility
Premature menopause is thoroughly discussed above. However, amenorrhea aside, the fertility rate after chemotherapy in those who maintain “normal” menstrual cycles is unknown. These women may have subtle endocrine defects in their menstrual cycles, resulting in decreased fertility.

Another potentially important issue in these women may be the window of fertility. Even when they maintain apparently normal menstrual cycles during and after chemotherapy, they may undergo earlier menopause than their peers. This has been documented in patients who receive chemotherapy during adolescence. They are advised to plan their families accordingly.[3]

Recently, more women have been inquiring about assisted reproductive techniques before chemotherapy to increase their chances of having genetic offspring in the future. In vitro fertilization is generally an option only for married women because the technique for long-term preservation of unfertilized eggs is currently unreliable, although fertilized embryos can be maintained. In vitro fertilization involves ovarian hyperstimulation with oral and systemic high-dose hormones to induce a menstrual cycle, which, in itself, could promote micrometastases. Nevertheless, if subsequent pregnancy after breast cancer treatment is proven to be safe, in vitro fertilization and storing fertilized embryos before chemotherapy could become more common for young breast cancer patients.

For many reasons, including the good of society and the value of human life, adoption is an excellent alternative. International adoption, in particular, has been easier for breast cancer survivors than has adoption of children from the United States.

Congenital Anomalies
There should be no greater risk of congenital anomalies among babies of women who conceive after breast cancer treatment. The authors’ discussion of the effects of chemotherapy on the fetus is accurate, but beside the point if the patient waits until after treatment to become pregnant. Needless to say, clinicians should discourage patients, in the strongest possible terms, from becoming pregnant during chemotherapy.

Breast-Feeding
Whether breast-feeding per se is protective against or conducive to carcinogenesis is not truly pertinent to these young women who have already developed the disease. No information is available about the effects of breast-feeding on distant recurrence of breast cancer, and there are minimal data on whether breast-feeding contributes to or inhibits local recurrence of breast cancer.

In the largest report to date, involving 13 patients, Higgins and Haffty found that the volume and duration of lactation from the treated breast were decreased, compared with the untreated breast. Local recurrence occurred in 2 of 13 women at 1 and 8 years after diagnosis, respectively.[4]

Monitoring for Breast Cancer Recurrence
I agree with the authors that pregnant women should be examined and followed for breast cancer recurrence in the same way as nonpregnant women. Nevertheless, I would obtain a history and perform a physical examination more frequently in pregnant women, perhaps every 3 months, so as to diagnose any recurrence earlier. The effect of the intense hormonal milieu of pregnancy on breast cancer recurrence is of great concern.

Risk of Recurrent Breast Cancer
The gold standard for answering questions about disease recurrence and survival in breast cancer patients who become pregnant is the prospective trial. Only retrospective surveys and population-based tumor registry studies have been performed thus far. The existing studies have shown no adverse effect and sometimes even a surprising beneficial effect on survival in women who become pregnant after breast cancer treatment.

Contrary to the Swedish study cited by Collichio et al, there is another multi-institutional study that has demonstrated a detrimental effect of pregnancy on subclinical breast cancer.[5] These authors postulated that subclinical breast cancer coexisted with pregnancy in young women who had been pregnant within 3 to 4 years before breast cancer diagnosis. The closer the antecedent pregnancy was to the breast cancer diagnosis, the worse was the prognosis, as compared with young breast cancer patients who had never been pregnant or had been pregnant more than 4 years prior to breast cancer diagnosis. The authors speculated that recent pregnancies (within the previous 4 years before breast cancer diagnosis) may be responsible for the more aggressive breast cancers seen in young women, considering that their pregnancy rate is so high (110 pregnancies per 1,000 women per year).

In summary, the effect of a subsequent pregnancy on slow-growing or dormant micrometastases is unknown and needs to be investigated in a prospective trial. A long-term goal of our research is to determine the effect of pregnancy (completed or incomplete) on disease-free recurrence.

Antiestrogen Therapy
Whether to prescribe tamoxifen (Nolvadex) in women with functioning ovaries is controversial. Tamoxifen treatment can cause endogenous estrogen levels to increase 10-fold. It is unknown whether the effect of tamoxifen in this situation is as beneficial as it is postmenopausal women. Among the premenopausal women treated at Memorial Sloan-Kettering Cancer Center, use of tamoxifen has been uncommon.

References:

1. Bjergaard JP: Long-term complications of cancer chemotherapy. J Clin Oncol 13:1534-1535, 1995.

2. Collichio F, Pandya K: Amenorrhea following chemotherapy for breast cancer: Effect on disease-free survival. Oncology 8:45-52, 1994.

3. Byrne J, Fears TR, Gail MH, et al: Early menopause in long-term survivors of cancer during adolescence. Am J Obstet Gynecol 166:788-793, 1992.

4. Higgins S, Haffty BG: Pregnancy and lactation after breast-conserving therapy for early stage breast cancer. Cancer 73:2175-2180, 1994.

5. Guinee VF, Olsson H, Moller T, et al: Effect of pregnancy on prognosis for young women with breast cancer. Lancet 343:1587-1589, 1994.