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Postmenopausal Breast Cancer Risk and Cumulative Number of Menstrual Cycles

¹ Julius Center for Health Sciences and Primary care, University Medical Center, Utrecht, the Netherlands and ² Netherlands Institute for Health Sciences, Rotterdam, the Netherlands

Requests for reprints: Petra H.M. Peeters, Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Room STR 6.1.31, P.O. Box 85060, 3508 BA Utrecht, the Netherlands. Phone: 31-30-250-9363, ext. 9384; Fax: 31-30-250-5485. E-mail: P.H.M.Peeters{at}umcutrecht.nl

Objective: To explore whether the lifetime cumulative number of menstrual cycles, as an index for total exposure to endogenous estrogens, and the number of menstrual cycles until a first full-term pregnancy (FFTP), are associated with breast cancer risk in postmenopausal women.

Methods: Population-based study with data from the Prospect-European Prospective Investigation into Cancer and Nutrition study. Naturally menopausal participants were eligible (n = 6,718). The cumulative number of menstrual cycles was computed in 6,031 (90%) women. We calculated the number of cycles until FFTP among parous participants. The number of menstrual cycles was impossible to compute in women who reported to be always irregular; therefore, we added the "always irregular" category in the analysis. During the 46,746 person-years of follow-up, 168 breast cancer cases were identified. Cox regression models were used and adjustments were made to account for potential confounders.

Results: Even when our data does not show a clear linear gradient, we observed an increased breast cancer risk in women with a higher number of cumulative menstrual cycles in their lifetime. Using 415 cycles as reference, the hazard ratio for the irregular group, 416-453, 454-490, and 491 cycles was 1.11 (.56, 2.19), 1.88 (1.14, 3.12), 1.74 (1.05, 2.87), and 1.80 (1.09, 2.96), respectively. Although not statistically significant, and of less magnitude, the risk estimates for the number of cycles before FFTP showed the same tendency.

Conclusion: Among women who underwent natural menopause, a higher number of menstrual cycles in lifetime, reflecting a longer exposure to endogenous estrogens, is associated with an increased breast cancer risk.

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