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Kathryn L. Terry, ScD; Walter C. Willett, MD, DrPH; Janet W. Rich-Edwards, ScD, MPH; Karin B. Michels, ScD, PhD

Arch Intern Med. 2006;166:2484-2489.

Background  Anovulation has been hypothesized to decrease the risk of breast cancer. Therefore, infertility attributed to ovulatory disorders and ovulation-induction therapy may influence breast cancer risk.

Methods  We analyzed prospectively collected data from the Nurses' Health Study II, a cohort of 116 671 female registered nurses aged 25 to 42 years at baseline. Information on infertility was assessed every 2 years starting in 1989, ovulation induction was assessed every 2 years from 1993 to 1997, and incident cases of breast cancer were included through 2001.

Results  During 1 275 566 person-years of follow-up (1989-2001), 1357 incident cases of invasive breast cancer were diagnosed. Overall, women who reported infertility due to ovulatory disorder had a significantly lower incidence of breast cancer than women who did not report problems conceiving during a 12-month period (covariate-adjusted hazard ratio, 0.75; 95% confidence interval, 0.59-0.96). The incidence of breast cancer was lowest among women with infertility due to ovulatory disorder who received ovulation-induction therapy (covariate-adjusted hazard ratio, 0.60; 95% confidence interval, 0.42-0.85).

Conclusions  Among women who participated in the Nurses' Health Study II, we observed an inverse association between infertility due to ovulatory disorder and breast cancer incidence. We observed the greatest reduction in the incidence of breast cancer for women who reported ovulatory disorder and use of ovulation-induction therapy, but these results should be interpreted with caution because these women may be the most infertile.

Author Affiliations: Departments of Epidemiology (Drs Terry, Willett, and Rich-Edwards) and Nutrition (Dr Willett), Harvard School of Public Health, Boston, Mass; Channing Laboratory, Department of Medicine (Drs Terry, Rich-Edwards, and Michels), and Obstetrics and Gynecology Epidemiology Center (Drs Terry and Michels), Brigham and Women's Hospital and Harvard Medical School, Boston; and Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School (Dr Rich-Edwards).

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