Early age at menopause and breast cancer: are leaner women more protected?A prospective analysis of the Dutch DOM cohort

To investigate the relationship between age at menopause, body mass index, and breast cancer risk, we used data from a prospective cohort study (DOM c ohort) in the Netherlands. Participants in this breast cancer-screening pro ject included 10,591 women living in Utrecht, aged 49-66 years at enrolment . During a median follow-up period of 19 years, women attended screening ro unds at which anthropometric measurements were taken and questions were ask ed about menopausal status, age at menopause, medication use and other risk factors for breast cancer. Cox regression analysis was used to investigate the relationship between age at menopause and subsequent breast cancer ris k. Breast cancer incidence decreased with an earlier age at menopause. Wome n with a menopausal age of 44 years or younger had a 34% lower risk of brea st cancer, than women with a menopausal age over 54 years (hazard ratio is 0.66 (95% confidence interval 0.43-0.91)). The annual hazard of breast canc er incidence decreased by 2.6% per year reduction in age at menopause. The protective effect of an early age at menopause was stronger for women with a low body mass index (less than or equal to 27 kg/m(2); reduction of 44%) than for women with a high body mass index (> 27 kg/m(2); reduction of 24%) , although this difference was not statistically significant (P for interac tion = 0.58). This difference was most pronounced in women who had ever smo ked. Adjustment for known breast cancer risk factors did not alter the crud e risk estimates significantly. In conclusion, this study provides evidence of the protective effect of low er age at menopause on subsequent breast cancer risk. This protective effec t may be even stronger in leaner women.