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Karin B. Michels, ScD, PhD; Kathryn L. Terry, ScD; Walter C. Willett, MD, DrPH

Arch Intern Med. 2006;166:2395-2402.

Background  A high body mass index (BMI) has been related to a reduced risk of breast cancer in premenopausal women. The mechanisms underlying this association have not been elucidated.

Methods  We explored whether factors affecting ovulation may explain the inverse association between BMI (calculated as weight in kilograms divided by the square of height in meters) and breast cancer in 113 130 premenopausal participants in the Nurses' Health Study II. During 1 225 520 person-years of prospective follow-up between 1989 and 2003, 1398 incident cases of invasive breast cancer were diagnosed. Weight, height, ovulatory infertility, menstrual cycle patterns, and a multitude of covariates were assessed throughout follow-up. Cox proportional hazards regression was used to compute hazard ratios and 95% confidence intervals (CIs).

Results  We observed a significant linear inverse trend between current BMI and breast cancer incidence (P<.001) that was not explained by menstrual cycle characteristics or infertility due to an ovulatory disorder (covariate-adjusted hazard ratio for breast cancer in women with a BMI 30 vs 20.0-22.4, 0.81; 95% CI, 0.68-0.96). We found BMI at age 18 years to be the strongest predictor of breast cancer incidence (covariate-adjusted hazard ratio for breast cancer in women with a BMI at age 18 years 27.5 vs 20.0-22.4, 0.57; 95% CI, 0.41-0.81).

Conclusions  Body size during the early phases of adult life seems to be particularly important in the development of premenopausal breast cancer. Factors other than anovulation are likely to mediate the protection conferred by a high BMI.

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

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