274 explaining the human breast cancer associations previously reported for CYP1A1 polymorphisms in relation to PCB exposure in middle-aged women [10–13]. In summary, in this study, the mixture of PCB congeners predicted the estimated effect of PCB exposure on risk of breast cancer. Overall, women in this study showed a variable distribution for the three PCB congeners that predicted breast cancer. Women with a high proportion of PCB 203 (top 25 % of the study population) relative to PCBs 167 and 187 had a nearly threefold increase in subsequent risk of breast cancer, compared to women with a lower proportion of PCB 203 (bottom 25 % of the study population). The relation of PCB exposure to breast cancer might be clariﬁed by additional laboratory, experimental and human population studies that account for timing of exposure in relation to windows of susceptibility for the breast and for concomitant host factors. It is likely to be particularly important to study congener mixtures and individual response to multiple exposures. It remains unclear whether individual differences in exposure, response to exposure, or both explain risk patterns observed. Acknowledgments This publication was made possible by the Breast Cancer and the Environment Research Program (BCERP) award number (U01 ES/CA 019471 to B.A.C. and M.B.T.), from the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI), NIH, DHHS; the National Cancer Institute award number (R01 CA72919 to B.A.C); and The National Institute of Child Health and Human Development award numbers (N01 HD 6 3258 and N01 HD 1 3334 to B.A.C.). Its contents are solely the responsibility of the authors and do not necessarily repre- sent the ofﬁcial views of the NIEHS or NCI, NICHD or the National Institutes of Health. We also gratefully acknowledge support of the Avon Foundation for this research, and our collaborators Mary Wolff who performed serum assays for this study, Robert Sholtz and Nikilou Krigbaum who prepared data ﬁles, Linda S. Birnbaum who provided comments on an earlier version of this manuscript, Barbara J. van den Berg, Roberta Christianson the late Frank Oechsli and the late Jacob Yerushalmy, Child Health and Development Studies founder, who together created and preserved the Child Health and Development Studies cohort. We also thank the National Institute of Child Health and Human Development, both current and past directors, Alan Guttmacher and Dwayne Alexander, and our project ofﬁcer, Gilman Grave for supporting the maintenance of the CHDS cohort. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract N01-PC35136 awarded to the Northern California Cancer Center, contract N01-PC- 35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Cen- ters for Disease Control and Prevention’s National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. 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