BRCA1 and BRCA2 Mutation Carriers Not at Greater Risk of Earlier Natural Menopause
Some data suggest that BRCA1 mutations are associated with occult primary ovarian insufficiency and that BRCA1 and BRCA2 mutation carriers have earlier natural menopause than noncarrier relatives. A study reported in Journal of Clinical Oncology by Ian M. Collins, MD, of Peter MacCallum Cancer Centre and University of Melbourne and colleagues indicates that BRCA1 and BRCA2 mutation carriers are not at greater risk of earlier natural menopause than their noncarrier relatives.
Study Details
The study involved women from multiple-case Australian and New Zealand breast cancer families in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. Eligible women had a documented pathogenic mutation, splice site mutation, or large deletion in BRCA1 or BRCA2 or were a blood relative of a mutation carrier who had tested negative for the identified family-specific mutation. Data were self-reported using questionnaires at entry and every 3 years thereafter.
Natural menopause was defined as the cessation of menses for 12 months without another cause. Cox proportional hazards analysis modeled time from birth to natural menopause, adjusting for multiple potential confounders, including year of birth, body mass index (BMI), parity, age at first birth, use of fertility drugs, regular cigarette smoking, and regular alcohol use. Analysis time was censored at the earliest of the following: last follow-up, bilateral oophorectomy, hysterectomy, commencement of hormone therapy, insertion of intrauterine device, or any cancer diagnosis.
BRCA1 carriers (n = 445) and noncarrier relatives (n = 559) and BRCA2 carriers (n = 374) and noncarrier relatives (n = 559) were well balanced for other baseline characteristics. Of the total 1,840 women included in the analysis, 344 (19%) reached natural menopause, with a median age of 51 years.
The median age at censoring for all women was 41 years; 788 were censored at last follow-up (without reaching natural menopause), 361 at cancer diagnosis, 223 at bilateral salpingo-oophorectomy or hysterectomy, 112 at first use of hormonal therapy including hormone replacement therapy or depot contraception, 6 at insertion of an intrauterine device, and 6 at first tamoxifen use or participation in a chemoprevention trial.
No Difference in Age-Specific Incidence of Menopause
A smaller proportion of BRCA1 carriers (11%) and BRCA2 carriers (13%) reached natural menopause compared with their noncarrier relatives (25% and 24%). More carriers were censored at cancer diagnosis (40% and 29% vs 7% and 7%). There was no difference between BRCA1 carriers vs noncarriers (adjusted hazard ratio [HR] = 1.03, P = .9) or between BRCA2 carriers and noncarriers (adjusted HR = 1.01, P = .9) in age-specific incidence of natural menopause.
Factors Associated With Risk
Later year of birth was independently associated with reduced age-specific risk of reaching natural menopause (HR = 0.87 per decade, P= .003), and smoking was associated with increased risk (HR = 1.30, P = .02). Hazard ratios for year of birth were similar for women from families with BRCA1 mutations (HR = 0.85, P = .02) and families with BRCA2 mutations (HR = 0.89, P = .06), and hazard ratios for smoking were similar for women from families with BRCA1 mutations (HR = 1.23, P = .2) and families with BRCA2 mutations (HR = 1.37, P =.06).
Use of fertility drugs was associated a borderline increased age-specific risk of reaching natural menopause for women from BRCA1 families (HR = 1.64; P = .06) but not for those from BRCA2 families (HR = 0.81, P = .6), and the difference was not significant (P = .2). BMI, alcohol use, and parity were not associated with risk of natural menopause (all P > .4).
The investigators concluded, “We found no evidence that BRCA1 and BRCA2 mutation carriers are at higher risk of natural menopause at a given age than their noncarrier relatives.”
Kelly-Anne Phillips, MD, of Peter MacCallum Cancer Centre and University of Melbourne is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
