Melbourne, Australia—Ever use of hormonal contraceptives appears to be associated with increased breast cancer (BC) risk for germline BRCA1 mutation carriers, especially if used for longer durations, according to a new study.

That was not the case, however, for BRCA2 mutation carriers, according to the study published in the Journal of Clinical Oncology.

Australian researchers from the University of Melbourne and colleagues used pooled observational data from four prospective cohort studies to determine associations between hormonal contraceptive use and BC risk for unaffected female BRCA1 and BRCA2 mutation carriers.

Of 3,882 BRCA1 and 1,509 BRCA2 mutation carriers, the researchers found that 53% and 71%, respectively, had ever used hormonal contraceptives for at least 1 year (median cumulative duration of use, 4.8 and 5.7 years, respectively). Overall, 488 BRCA1 and 191 BRCA2 mutation carriers developed BC during the study’s median follow-up of 5.9 and 5.6 years, respectively.

“Although for BRCA1 mutation carriers, neither current nor past use of hormonal contraceptives for at least 1 year was statistically significantly associated with BC risk (hazard ratio [HR], 1.40 [95% CI, 0.94 to 2.08], P = .10 for current use; 1.16 [0.80 to 1.69], P = .4, 1.40 [0.99 to 1.97], P = .05, and 1.27 [0.98 to 1.63], P = .07 for past use 1-5, 6-10, and >10 years before, respectively), ever use was associated with increased risk (HR, 1.29 [95% CI, 1.04 to 1.60], P = .02),” the authors wrote. “Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, P = .002) for each additional year of use.”

The researchers added, “For BRCA2 mutation carriers, there was no evidence that current or ever use was associated with increased BC risk (HR, 0.70 [95% CI, 0.33 to 1.47], P = .3 and 1.07 [0.73 to 1.57], P = .7, respectively).”

The authors suggested that decisions about the use of hormonal contraceptives in women with BRCA1 mutations should be made after carefully weighing the risks and benefits for each individual.

Background information in the article advises that women with a germline mutation in BRCA1 or BRCA2 have high lifetime risks of BC. The average lifetime risk is approximately 70%, with more than one-half of all breast cancers in these women occurring before 50 years of age. “Understanding whether and how use of hormonal contraception (HC) might affect these risks is important for informed decision making,” the researchers pointed out.

The researchers found that hormonal contraceptive use in BRCA1 mutation carriers was associated with increased risk of BC, with users having a proportional increase in risk of 3% for each year of hormonal contraceptive use.

“These results should be discussed with young women carrying a BRCA1 mutation as they make contraceptive choices prior to prophylactic salpingo-oophorectomy,” the authors advised.

Hormonal contraceptives include oral contraceptive pills (OCPs), hormonal implants, injections, and intrauterine devices. The products, which are efficient in providing contraception, are used in the treatment of polycystic ovarian syndrome, premenstrual dysphoric disorder, and endometriosis and reduce risks of ovarian and endometrial cancers.

“In the general population, current use of HC is associated with a 20%-30% relative increase in the risk of BC compared with never having used HC,” according to the study. “Longer duration of use is associated with higher risk and, although the relative risk reduces after cessation, it remains elevated for 5-10 years after cessation. Most published data refer only to various formulations of the OCP, but associations are similar for progestogen-only contraceptives.”

Past studies of the association between OCP use and BC risk for BRCA1 and BRCA2 mutation carriers have assessed ever use rather than current use and come up with conflicting findings, according to the authors.

This study assessed the association between use of any hormonal contraceptive and BC risk for BRCA1 and BRCA2 mutation carriers using individual participant data from four prospective cohorts. The researchers hypothesized that the association between current hormonal contraceptive use and BC risk would not differ from that for the general population. In addition, they stated that duration of use, age at first use, and use before first birth would not be associated with BC risk independently of current use and recency of use.

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