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Association between Plasma 25-Hydroxyvitamin D and Breast Cancer Risk

¹ Department of Medicine, Division of Hematology/Oncology, College of Physicians and Surgeons, ² Department of Epidemiology, Mailman School of Public Health, ³ Herbert Irving Comprehensive Cancer Center, ⁴ Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, ⁵ Department of Biostatistics, Mailman School of Public Health, and ⁶ Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University; ⁷ Department of Community and Preventive Medicine, Mt. Sinai School of Medicine, New York, New York; ⁸ Department of Epidemiology, University of North Carolina, School of Public Health, Chapel Hill, North Carolina; and ⁹ Department of Epidemiology and Biostatistics, Arnold School of Public Health, Columbia, South Carolina

Requests for reprints: Katherine D. Crew, Department of Medicine, Division of Hematology/Oncology, Columbia University, 161 Fort Washington Avenue 10-1072, New York, NY 10032. Phone: 212-305-1732; Fax: 212-305-0178; E-mail: kd59{at}columbia.edu.

Vitamin D has been associated with decreased risk of several cancers. In experimental studies, vitamin D has been shown to inhibit cell proliferation and induce differentiation and apoptosis in normal and malignant breast cells. Using a population-based case-control study on Long Island, New York, we examined the association of breast cancer with plasma 25-hydroxyvitamin D (25-OHD) levels, a measure of vitamin D body stores. In-person interviews and blood specimens were obtained from 1,026 incident breast cancer cases diagnosed in 1996 to 1997 and 1,075 population-based controls. Plasma 25-OHD was measured in batched, archived specimens by Diasorin RIA. The mean (SD) plasma 25-OHD concentration was 27.1 (13.0) and 29.7 (15.1) ng/mL in the cases and controls, respectively (P < 0.0001). Plasma 25-OHD was inversely associated with breast cancer risk in a concentration-dependent fashion (P_trend = 0.002). Compared with women with vitamin D deficiency (25-OHD, <20 ng/mL), levels above 40 ng/mL were associated with decreased breast cancer risk (odds ratio, 0.56; 95% confidence interval, 0.41-0.78). The reduction in risk was greater among postmenopausal women (odds ratio, 0.46; 95% confidence interval, 0.09-0.83), and the effect did not vary according to tumor hormone receptor status. In summary, these results add to a growing body of evidence that adequate vitamin D stores may prevent breast cancer development. Whereas circulating 25-OHD levels of >32 ng/mL are associated with normal bone mineral metabolism, our data suggest that the optimal level for breast cancer prevention is 40 ng/mL. Well-designed clinical trials are urgently needed to determine whether vitamin D supplementation is effective for breast cancer chemoprevention.

Key Words: vitamin D • breast cancer risk • chemoprevention