Cumulative number of menstrual cycles and breast cancer risk: results from the E3N cohort study of French women

Objective: To examine the relationship between breast cancer risk and the cumulative number of cycles before a first full-term pregnancy (FTP) and lifetime, taking age at menarche and at onset of regular cycling, periodicity and regularity of cycles, duration of periods of pregnancy, and lactation, oral contraceptive (OC) use, and age at menopause into account. Methods: The data were taken from the E3N prospective cohort study of women aged 40–65 years in 1990. A total of 1718 breast cancer cases were identified during the 579,525 person-years of follow-up. Results: There was a highly significant linear relationship between breast cancer risk and both the cumulative number of cycles before a first FTP (p for trend < 0.0001) and lifetime (p for trend < 0.001), with multivariate relative risk (RR) of a similar magnitude for both variables. Compared to women with a lifetime number of cycles ≤ 402 ( ≤ 30 years), the RR for those with a lifetime total of 403–441, 442–480, 481–520, and ≥ 521 cycles were 0.95 (0.75–1.21), 1.21 (0.97–1.52), 1.23 (0.96–1.58), and 1.60 (1.25–2.04), respectively. Results restricted to never OC users were similar. Conclusions: Further investigation is needed to clarify whether the underlying factor is repeated exposure to fluctuating hormones, the number of anovular/ovular cycles, or the relative importance of the follicular and luteal phases.