Germline BRCA-Mutated Breast Cancer Does Not Increase Risk of Adverse Pregnancy Outcomes

Women who have had germline BRCA-mutated breast cancer before the age of 40 were shown in a recent study to be able to have subsequent pregnancies without increasing their risk for disease recurrence, report results published in Journal of Clinical Oncology.

“To our knowledge, this is the largest study to date specifically designed to address several unmet questions related to the safety of pregnancy after breast cancer in patients with germline BRCA mutations and their reproductive outcomes,” the study authors said in a statement announcing their results.

They have done prior research on pregnancy in women with breast cancer but had not focused specifically on reproductive outcomes in younger women with the germline BRCA-mutated subtype, who are increasingly choosing to hold off on pregnancy or trying to become pregnant even before their cancer is diagnosed, the statement noted.

This international multicenter hospital-based retrospective cohort study addressed that knowledge gap by evaluating pregnancy outcomes for 1252 women with a history of invasive early-onset germline BRCA-mutated breast cancer from 30 referral centers worldwide. Sixty-five percent of the women had a BRCA1 mutation, 34% had a BRCA2 mutation, and 0.9% had BRCA1/2 mutations, and their breast cancer was diagnosed between January 2000 and December 2012.

The primary study outcomes were pregnancy rate and disease-free survival (DFS) between 2 cohorts: pregnancy following breast cancer and no pregnancy. Secondary outcomes were pregnancy outcome and overall survival (OS). Each patient in the pregnancy group was matched to 3 nonpregnant controls based on DFS, diagnosis year, nodal status, hormone receptor status, and BRCA mutation.

Results show that 10 years following their diagnosis, 19% (n = 195; 95% CI, 17%-22%) of the women had at least 1 pregnancy. Of these, 8.2% (n = 16) had an induced abortion and 10.3% (n = 20) had a miscarriage. Among the 76.9% (n = 150) of women who ultimately gave birth, 170 babies were born. The median (interquartile range [IQR] time between diagnosis and pregnancy was 4.5 (IQR, 3.16-6.7) years overall, but 6.3 (IQR, 4.3-7.7) and 4.0 (IQR, 2.7-5.6) years, respectively, for hormone receptor—positive and –negative disease.

There were few pregnancy complications (11.6%; n = 13) or congenital abnormalities (1.8%; n = 2) in the pregnancy cohort. These women were also younger than the nonpregnancy cohort (P < .001), with more BRCA1 mutations (P = .01), node-negative disease P = .003), and hormone receptor—negative disease (P = .002).

The median follow-up was 8.3 years, with almost equal DFS (adjusted HR [aHR], 0.87; 95% CI, 0.61-1.23; P = .41) and OS (aHR, 0.88; 95% CI, 0.50-1.56; P = .66) rates seen between the pregnancy and nonpregnancy study groups. Both of these measures were based on time since diagnosis. Chemotherapy also did not affect outcomes for the 95.3% of patients in both groups who underwent the treatment.

“We observed that pregnancy after breast cancer is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes,” the authors concluded. “These results provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility.”

Due to the greater chance of congenital abnormalities, preterm birth, and perinatal complications that accompany survivors of breast cancer who have a pregnancy, the authors believe these outcomes require further study. Contraception should also be discussed with those patients not desiring a pregnancy.

Reference

Lambertini M, Ameye L, Hamy A-S, et al. Pregnancy after breast cancer in patients with germline BRCA mutations. J Clin Oncol. Published online July 16, 2020. doi:10.1200/JCO.19.02399