Hormonal Contraception Linked to Increased Breast Cancer Risk in BRCA1 Carriers

Carriers of the BRCA1 cancer gene had a significantly increased risk of breast cancer if they used hormonal contraception (HC), pooled cohort data showed.

Breast cancer risk increased by 29% in BRCA1 carriers who reported any use of HC during at least one 12-month continuous period. The risk also increased with duration of HC use, but separate analyses showed no increased risk associated with current use within the past year, 1-5 years in the past, 6-10 years before, or more than 10 years.

The analysis showed no evidence of increased breast cancer risk for BRCA2 carriers who used HC, reported Kelly-Anne Phillips, MD, MBBS, of Peter MacCallum Cancer Center in Melbourne, Australia, and co-authors in the Journal of Clinical Oncology.

“When counseling women, absolute risks are more useful than relative risks,” the authors noted in their discussion of the findings. “These absolute risks will be different for different women, so incorporating our findings into risk prediction models such as CanRisk would assist in providing personalized estimates.”

“Decisions about use of HC in women at increased risk for BC [breast cancer] due to BRCA1 mutations need to carefully weigh the absolute risks and benefits,” they added. “While shorter-term use may result in only small increases, prolonged cumulative use may result in larger increases in absolute BC risk that may not be acceptable to some women.”

An individualized approach to patient counseling about breast cancer risk in BRCA1 carriers is advisable, agreed Yara Abdou, MD, of the University of North Carolina and Lineberger Comprehensive Cancer Center in Chapel Hill.

“These results suggest that for BRCA1 mutation carriers, HC use should be approached with caution, particularly for prolonged durations,” Abdou told MedPage Today via email. “Clinicians should engage in detailed risk-benefit discussions with BRCA1 carriers considering HC use, emphasizing the potential increased risk of breast cancer.”

“For BRCA2 carriers, the lack of a significant association suggests a lower risk; however, the relatively small number of breast cancer cases in this group warrants cautious interpretation.”

The observational design of the study limits the ability to establish a causal relationship between HC use and breast cancer in BRCA1 carriers, Abdou noted. Additionally, the median follow-up of 5.9 years for BRCA1 carriers and 5.6 years for BRCA2 carriers might not be long enough to capture the long-term effects of HC use on breast cancer risk.

“Overall, this study adds to the growing body of evidence suggesting that HC use can elevate breast cancer risk for BRCA1 mutation carriers, underscoring the importance of personalized risk assessment and contraceptive counseling,” she said.

Carriers of germline BRCA mutations have a 70% lifetime risk of developing breast cancer, which occurs before age 50 in half of cases, Phillips and co-authors noted in their introduction. In the general population, current HC use is associated with a 20-30% increase in relative risk of breast cancer as compared with never users, and the risk increases with duration of HC use. Breast cancer risk remains elevated for as long as 10 years after discontinuation.

Prior studies of oral contraceptive pill use in BRCA carriers have often involved small patient numbers and yielded inconsistent findings. Oral contraceptive pills represent only one type of HC, and no studies have examined breast cancer risk with any HC use in BRCA carriers. Phillips and colleagues sought to address that data void.

Using pooled data from four prospective cohort studies, investigators analyzed breast cancer risk in 3,882 BRCA1 carriers and 1,509 BRCA2 carriers who had used HC for at least 1 year (median cumulative duration 4.8 and 5.7 years, respectively). About half of the BRCA1 carriers and 71% of the BRCA2 carriers reported HC use during at least one continuous 12-month period.

During follow-up, 488 BRCA1 carriers and 191 BRCA2 carriers developed breast cancer, including 440 and 151 invasive cancers, respectively. A comparison of current and past use of HC among BRCA1 carriers versus never users showed numerically increased risks of breast cancer among users, but none of the values achieved statistical significance, including use within the past year (HR 1.40, 95% CI 0.94-2.08), use in the past 1-5 years (HR 1.16, 95% CI 0.80-1.69), use in the past 6-10 years (HR 1.40, 95% CI 0.99-1.97), or use more than 10 years in the past (HR 1.27, 95% CI 0.98-1.63).

Assessment of HC use as a binary variable showed that ever use was associated with a significantly increased risk of breast cancer versus never use (HR 1.29, 95% CI 1.04-1.60, P=0.02). Breast cancer risk also increased by increasing duration of HC use, 3% for each additional year of use (P=0.002).

Analyses involving BRCA2 carriers showed no association for current or ever use of HC and increased breast cancer risk (HR 0.70, 95% CI 0.33-1.47 and HR 1.07, 95% CI 0.73-1.57, respectively).