Breast cancer genes modify age at menopause

By Lynda Williams, Senior mewireNews Reporter

Women with the BRCA1 or BRCA2 mutation begin menopause at a significantly younger median age than noncarriers, US researchers warn.

The median age at time of natural menopause was 50 years in a group of 382 White BRCA1/2 carriers from Northern California compared with 53 years in a control group of 765 White women from the same region, report Mitchell Rosen, from the University of California at San Francisco, and co-authors.

"In addition to discussing risk-reducing salpingo-oophorectomy, we would encourage the early initiation of fertility counseling for BRCA1/2 carriers and the consideration of earlier childbearing," they recommend in Cancer.

The trend towards earlier menopause in BRCA1/2 carriers remained true after adjusting for parity, smoking, and oral contraceptive use, with multivariate analysis of complete data sets on 228 BRCA1/2 carriers and 759 controls giving a significant hazard ratio (HR) of 4.06.

Indeed, the HR continued to demonstrate earlier age at menopause in BRCA1/2 carriers than controls after the researchers excluded women whose menopause was induced by surgery, chemotherapy, or radiotherapy, and adjusted for parity, smoking, and oral contraceptive use (49 vs 53 years, HR=4.33).

The impact of BRCA1/2 was particularly noticeable for women who smoked, with menopause beginning at a median of 48 years in BRCA1/2 carriers who currently smoke compared with 51 years in current smoking controls.

BRCA1/2 carriers who were heavy smokers (≥20 cigarettes/day) entered menopause at a median of 46.0 years compared with 49.0 years in nonsmoker or past smokers with the mutations. The median age was 48.5 years for light smokers (<10 cigarettes/day) and 50.0 years for moderate smokers (10-19 cigarettes/day).

While the study showed that BRCA1/2 carriers had fewer children than controls, the team acknowledges that parity does not account for women in either population who tried and failed to conceive, or the age at time of attempting conception.

Noting previous research has indicated BRCA1 may be associated with low ovarian reserve, they comment: "These findings are of interest given that a lower ovarian reserve has been associated with infertility and an earlier age of onset of menopause.

"Future studies are needed to clarify whether fertility is compromised among BRCA1/2 carriers."

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