Carrying a BRCA Mutation Does Not Prevent Pregnancy After Breast Cancer Treatment

BRCA Mutations and Breast Cancer: Concerns About Pregnancy

BRCA1 and BRCA2 gene mutations are genetic factors that substantially increase breast cancer risk. Carriers worry not only about cancer but also about future pregnancy plans. Many women with BRCA mutations have major concerns about the safety of pregnancy after treatment and the possibility of cancer recurrence. These include treatment side effects, passing genetic risk to children and the effects of changing hormone levels, particularly in hormone receptor-positive breast cancer.

BRCA1 and BRCA2 mutations follow an autosomal dominant inheritance pattern: a parent carrying a mutation has a 50% chance of passing it to a child. These mutations increase susceptibility to certain cancers, particularly breast and ovarian cancer, so genetic counseling is recommended for people with a family history.

Inherited gene mutations account for 10-15 percent of breast cancers. BRCA1 and BRCA2 mutations account for about 80-90 percent of these hereditary breast cancers.

Studies of Pregnancy Concerns Among BRCA Carriers

Recent research has helped clarify pregnancy and fertility concerns among BRCA mutation carriers.

Among women carrying BRCA mutations, a literature review found differing results on the mutations' effects on fertility and the impact of cancer treatment and preventive surgery on reproductive potential. Some studies reported reduced ovarian reserve in BRCA-positive women, indicated by low anti-Müllerian hormone (AMH) levels and poorer responses to ovarian stimulation. This affects reproductive decisions among women diagnosed with BRCA mutations.

In breast cancer patients carrying BRCA mutations, another review examined fertility and pregnancy issues. It addressed the role of BRCA mutations in breast cancer and their effects on reproductive potential, the safety and effectiveness of fertility preservation strategies, and whether pregnancy after diagnosis is possible.

Pregnancy after breast cancer treatment in BRCA1/2 mutation carriers has also been observed to have no adverse effect on pregnancy and birth outcomes compared with the general population. BRCA1/2-positive breast cancer patients previously exposed to cancer treatment were reported not to have higher risks of congenital abnormalities or miscarriage than the general population.

These findings help us better understand the particular fertility and pregnancy challenges and concerns faced by BRCA carriers. However, further research is needed, and patients' needs, oncofertility counseling and preservation strategies should be carefully addressed before treatment begins.

A Recent Study Presented at SABCS

Research presented by Dr. Matteo Lambertini and colleagues at the San Antonio Breast Cancer Symposium 2023 (SABCS), and published simultaneously in JAMA , reported that no adverse pregnancy outcomes were observed in BRCA1/2 mutation carriers treated for breast cancer. This provides reassuring evidence for oncofertility counseling when young BRCA carriers wish to become pregnant after breast cancer diagnosis and treatment.

A mind map summarizing the article and study is shown below:

Study Details

This retrospective study included women diagnosed with stages 1-3 breast cancer between 2000 and 2020 who were aged 40 or younger, a total of 4732 patients . They carried germline BRCA1 and/or BRCA2 mutations.

Overall, 659 patients became pregnant after diagnosis and treatment, while 4073 did not. Those in the pregnancy group were younger at breast cancer diagnosis (median age, 30 vs 35), more often had node-negative disease (62.5% vs 52.1%) and more often had hormone receptor (HR)-negative disease (66.7% vs 52.3%).

Pregnancy Frequency and Outcomes

• Patients were followed for a median of 7.8 years.
• The cumulative incidence of pregnancy at ten years was 22%.
• The median time from breast cancer diagnosis to pregnancy was 3.5 years, and
• 27.8% of pregnancies occurred after 5 years.
• At 10 years, cumulative pregnancy incidence was 18% in HR-positive disease and 26% in HR-negative disease (P <0.001). Time from diagnosis to pregnancy was 4.3 and 3.2 years, respectively (P <0.001). The proportions of pregnancies occurring after five years were 39.8% and 22.0%, respectively.
• Overall, median age at pregnancy was 34.7; 79.2% conceived spontaneously without assisted reproductive technology, and 79.7% gave birth.
• Miscarriage occurred in 9.7%, and 6.9% chose to terminate their pregnancy. Most patients (86.3%) had no pregnancy complications.

Dr. Lambertini noted, "Overall, the rate of pregnancy complications was the same as, or even lower than, what we would expect in healthy women in the general population."

Survival Analyses

The initial analysis found no significant difference in disease-free survival between women who became pregnant and those who did not. This was observed both in the unadjusted analysis (hazard ratio 0.97; 95% confidence interval [CI], 0.82-1.15) and in an analysis adjusted for geographic region, age, lymph node status, hormone receptor [HR] status and type of breast surgery (hazard ratio 0.99; 95% CI, 0.81-1.20).

In a secondary analysis, the researchers matched patients who became pregnant with those who did not according to disease-free interval, BRCA gene type, hormone receptor status, lymph node status and year of diagnosis.

After this detailed matching, the pregnancy group showed a statistically significant improvement in disease-free survival compared with the nonpregnancy group (hazard ratio 0.63; 95% confidence interval [CI], 0.53-0.74).

Patients in the pregnancy group also showed significantly better breast cancer-specific survival in unadjusted (hazard ratio 0.53; 95% CI, 0.37-0.74), adjusted (hazard ratio 0.60; 95% CI, 0.40-0.88) and matched analyses (hazard ratio 0.43; 95% CI, 0.30-0.63).

Overall survival was likewise significantly better in unadjusted (hazard ratio 0.52; 95% CI, 0.38-0.72), adjusted (hazard ratio 0.58; 95% CI, 0.40-0.85) and matched analyses (hazard ratio 0.43; 95% CI, 0.30-0.61).

These findings suggest that pregnancy is no longer contraindicated for young BRCA carriers after appropriate breast cancer treatment and follow-up.