Internal Doses of PCB153 Estimated for Different Exposure Windows During Womenʼs Lifetime are Inversely Associated With the Incidence of Breast Cancer

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O-29B4-3 Background/Aims: Endocrine disrupting chemicals such as polychlorinated biphenyls (PCBs) have been suspected to play a role in breast cancer etiology, but epidemiologic studies have generally failed to detect an association between biological levels of PCBs and breast cancer. Measuring PCBs close to the time of cancer diagnosis and not assessing exposure during key periods of mammary gland development, eg, during childhood and adolescence, constitute major limitations, and may hinder the possibility of detecting an association between exposure and disease. We studied the relation between breast cancer risk and biological levels of PCB153 estimated during different exposure windows in the women's lifetime. Methods: We conducted a case-control study including 1079 incident cases of breast cancer and 1055 population controls, who elicited a detailed questionnaire and gave a blood specimen during interview. Based on serum levels, the individual lifetime profiles for PCB153 internal doses were simulated using a physiologically-based pharmacokinetic framework that integrates information on age, height, weight changes over lifetime, pregnancies, and breastfeeding history. Logistic regression models were used to calculate odds ratios for breast cancer associated with PCB153 levels estimated during the first to the fifth decade of life, obtained from the pharmacokinetic profiles, and adjusting for age and reproductive risk factors. Results: The odds ratio of breast cancer for women in the highest exposure quartile of PCB153 measured at recruitment in the study was 0.73 (0.54–0.99), as compared to women in the lowest exposure quartile. Using physiologically-based pharmacokinetic models had only weak influence on the findings, as the odds ratios were also below unity when women were classified according to simulated levels of PCB153 in different decades of life. Conclusion: The inverse association with breast cancer confirms previous findings, possibly reflecting the effect of unmeasured environmental factors that correlate with PCB153, or a possible protective role resulting from AhR stimulation by PCBs.