Increased mortality risk for BRCA carriers diagnosed within 10 years postpartum

Key takeaways:

• BRCA carriers diagnosed within 10 years vs. 10 years or more postpartum had an increased all-cause mortality risk.
• BRCA1 vs. BRCA2 carriers diagnosed within 10 years postpartum had higher mortality risk.

Women with breast cancer and germline BRCA pathogenic variants had increased all-cause mortality risk if diagnosis occurred within 10 years postpartum, according to cohort study results published in JAMA Network Open.

“An emerging body of work suggest that the postpartum period is a high-risk window for initiation of new cancers and the rapid progression of subclinical lesions to cancers with metastatic phenotypes. Meta-analyses of young-onset breast cancer showed a postpartum diagnosis up to 10 years after childbirth was consistently associated with increased risk of distant metastasis and death,” Zhenzhen Zhang, PhD, MPH, assistant professor in the division of oncological sciences at the Knight Cancer Institute at Oregon Health & Science University, and colleagues wrote. “Given that proximity to recent childbirth is such a strong factor associated with breast cancer metastasis and survival in the general population, the question of whether women with hereditary pathogenic variants in breast cancer predisposing genes have similarly poorer prognosis merits investigation.”

Zhang and colleagues conducted a prospective cohort study with data from 903 women (mean age at diagnosis, 34.7 years) with germline BRCA1 and BRCA2 pathogenic variants diagnosed with stage I to III breast cancer at age 15 to 45 years in the U.K. All women had complete data on time since recent childbirth. Researchers evaluated time between most recent childbirth and subsequent breast cancer diagnosis and its association with all-cause mortality.

During a mean follow-up period of 10.8 years, 419 women were diagnosed with breast cancer within 10 years postpartum, of whom 228 were diagnosed less than 5 years postpartum and 191 were diagnosed 5 to less than 10 years postpartum.

Women diagnosed with breast cancer within 5 to less than 10 years postpartum had an increased all-cause mortality risk compared with nulliparous women and those diagnosed 10 years or longer postpartum (HR = 1.56; 95% CI, 1.05-2.3). Compared with nulliparous women, those with estrogen receptor-positive breast cancer diagnosed within 5 years postpartum (HR = 2.35; 95% CI, 1.02-5.42) and women with estrogen receptor-negative breast cancer diagnosed within 5 to less than 10 years postpartum (HR = 3.12; 95% CI, 1.22-7.97) had greater all-cause mortality risk.

All-cause mortality risk was higher among BRCA1 carriers diagnosed within 5 to less than 10 years postpartum compared with BRCA2 carrier counterparts (HR = 2.03; 95% CI, 1.15-3.58).

“Consideration of the potential impact of childbirth on breast cancer outcomes in young germline BRCA pathogenic variant carriers may improve standard of care within the realms of genetic counseling, disease prevention and the clinic,” the researchers wrote.