Exposure to polychlorinated biphenyl (PCB) congeners during pregnancy and subsequent risk of breast cancer before age 50

Discrete windows of susceptibility to toxicants have been identified for the breast, including in utero, puberty, pregnancy and postpartum. We tested the hypothesis that exposure to polychlorinated biphenyls (PCBs) during pregnancy is associated with increased risk of breast cancer diagnosed before age 50 in a nested case-control study in the Child Health and Development Studies pregnancy cohort (N=129 cases matched to controls on birthyear). We analyzed archived early postpartum serum samples collected an average of 17 years before diagnosis (mean diagnosis age=43 years) for 16 PCB congeners. We used conditional logistic regression to adjust for lipids, race, year, lactation and body mass. The mixture of congeners was variable and we observed strong breast cancer associations with three main congeners. PCB 167 was associated with a lower risk (Odds Ratio (OR), 75th vs. 25th percentile=0.2, 95% confidence interval (95%CI)=0.1, 0.8) as was PCB 187 (OR, 75th vs. 25th percentile=0.4, 95% CI= 0.1, 1.1). In contrast, PCB 203 was associated with a 6-fold increased risk (OR, 75th vs. 25th percentile=6.3, 95%CI=1.9, 21.7). The net effect of PCB exposure was nearly a tripling of breast cancer risk (OR, 75th vs. 25th percentile=2.8 95%CI=1.1, 7.1) among women with a higher proportion of PCB 203 in relation to the sum of PCBs 167 and 187. PCB exposure in pregnancy may be associated with increased risk for early breast cancer depending on the mixture that represents internal dose. It remains unclear whether individual differences in exposure, response to exposure, or both explain risk patterns observed.