CancerCauses and Control, 3, 503 - 512 Carotenoids, retinol, and vitamin E and risk of proliferative benign breast disease and breast cancer Stephanie J. London, Evan A. Stein, I. Craig Henderson, Meir J. Stampfer, William C. Wood, Steven Remine, Jan R. Dmochowski, Nicholas J. Robert, and Walter C. Willett (Received 26 May 1992;acceptedin revised form 4 August 1992) We investigated the relationship between serum levels of retinol, 13-carotene, ~-carotene, lycopene, a-toco- pherol, and ~/-tocopherol as well as intakes of retinol, carotene, and vitamin E and the risks of breast cancer and proliferative benign breast disease (BBD) in a case-control study of postmenopausal women in the Bos- ton, MA (United States) area. Serum nutrient data were available for 377 women with newly diagnosed stage I or II breast cancer and 173 women with proliferative BBD. Controls were 403 women who were evaluated at the same institutions but did not require a breast biopsy or whose biopsy revealed nonproliferative BBD. We observed no significant associations between serum levels of these micronutrients and risk of proliferative BBD or breast cancer. The risk of breast cancer was decreased among women in the highest quintile of intake of vitamin E from food sources only (odds ratio [OR] for the highest quintile --- 0.4, 95 percent confidence interval [CI] -- 0.2-0.9; P, trend across quintiles = 0.02) but less so for total vitamin E intake including sup- plements (OR = 0.7, CI = 0.4-1.3; P, trend = 0.07). Key words: oc-carotene, o~-tocopherol, benign breast disease, B-carotene, breast cancer, dietary intake, ~/-tocophe- rol, lycopene, serum, United States. Introduction Vitamin A and related compounds play an important role in cell differentiation and, therefore, are hypothe- sized to influence carcinogenesis, l Dietary carote- noids, which include precursors of vitamin A, also may mediate cancer risk by this mechanism or, as with vit- amin E, by antioxidant properties. 2 Extensive experi- mental evidence indicates that certain natural and synthetic retinoids inhibit mammary carcinogenesis in Dr London is with the Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. Dr Stein is with Medical Research Laboratories, Cincinnati, OH, USA. Dr Henderson was with the Dana Farber Cancer Center and the Department of Medicine, Harvard Medical School, Boston, MA, USA, and is currently with the University of California at San Francisco, San Francisco, CA, USA. Drs Stampfer and Willett are with the Department of Epidemiology, Harvard School of Public Health, Boston, MA, and the Channing Laboratory, Department of Medicine at Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Dr Willett is also with the Department of Nutrition, Harvard School of Public Health, Boston, MA. Dr Wood was with the Department of Surgery, Massachusetts General Hospital, Boston, MA, and is currently with the Department of Surgery, Emory University, Atlanta, GA, USA. Dr Remine was with the Department of Surgery, Lahey Clinic, Burlington, MA, and is currently with Health Cleveland, Fairview General Hospital, Cleveland, OH. Dr Robert was with the Department of Medicine, New England Medical Center, Tufts University, Boston, MA, and is currently with the Division of Hematol- ogy/Oncology, Fairfax Hospital, Fall Church, VA, USA. Dr Dmochowski is with the Department of Surgery, Lahey Clinic, Burlington, MA. Address correspondenceto Dr Stephanie London, USC School of Medicine, PMB B306, 1420 San Pablo St, Los Angeles, CA 90033, USA. This project was supported by research grant CA 40429from the National Cancer Institute. Dr London was supported in part by an Institutional National Research Service Award (CA 09001) from the National Cancer Institute. © 1992 Rapid Communications of Oxford Ltd Cancer Causes and Control. Vol 3. 1992 503