PCB 167 187 203 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 1.00 1.09 (0.48, 2.47) 0.70 (0.27, 1.78) 0.24** (0.07, 0.79) 1.00 0.94 (0.41, 2.17) 0.92 (0.36, 2.38) 0.35* (0.11, 1.14) 1.00 1.21 (0.46, 3.18) 2.89** (0.98, 8.55) 6.34 (1.85, 21.73) \0.04 \0.02 \0.001 1.00 1.26 (0.53, 3.00) 1.52 (0.64, 3.62) 3.01 (1.34, 6.78) 1.00 1.23 (0.53, 3.07) 1.53 (0.64, 3.68) 3.09 (1.34, 7.16) 1.00 1.36 (0.53, 3.52) 1.78 (0.70, 4.55) 2.81 (1.11, 7.09) CI conﬁdence interval a A post-hoc PCB score was deﬁned to describe the net effect of PCB exposure in this study sample (described in text). PCB 203 was associated with increased risk, while PCBs 167 and 187 were asso- ciated with decreased risk (see ﬁnal model, Table 2). Therefore, the PCB score was deﬁned as the proportion of PCB 203 relative to the sum of PCBs 167 and 187: PCB 203/(PCB 167 ? PCB 187). N = 112 age-matched case–control pairs for all models shown Each of the three PCBs is coded as quartiles, based on the distribution in controls. Quartile 1 is the reference category and quartiles 2, 3, 4 are entered as dummy variables for each PCB shown. Associations shown are based on a single model where quartile terms for all PCBs are entered. P value for trend is estimated from a linear model where all three PCBs are entered as continuous variables. N = 112 case– control pairs CI conﬁdence interval, p signiﬁcance probability * p B 0.10 ** p B 0.05 p B 0.01 Table 4 Estimated net effects of PCB exposure on risk of breast cancer before 50 years of age Quartile of PCB scorea Odds ratio (95 % CI) Level of adjustment Unadjusted Cholesterol and triglycerides Cholesterol, triglycerides, race, parity, lactation, body mass index, and year of blood sampling Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Breast Cancer Res Treat (2012) 136:267–275 Table 3 Associations of PCB 167, 187, and 203 with breast cancer diagnosed before 50 years of age Quartile Odds ratio (95 % CI) p value for linear trend 271 Based on the results in Tables 2 and 3, a PCB score was constructed as the ratio of PCB 203 (positively related to risk) to the sum of PCBs 167 and 187 (each negatively related to risk). The PCB score was highly variable in the cohort, ranging from 8 % PCB 203 (compared to the sum of PCBs 187 and 167) to 131 % PCB 203. Overall for cases and controls combined, the median of the 4th quartile (0.67) was 2.3 times higher than the median of the 1st quartile (0.30). Among controls, the median of the 4th quartile of the PCB score (0.61) was 2.5 times higher than the median of the 1st quartile of the PCB score (0.25). Among cases, the median of the 4th quartile of the PCB score (0.71) was 2.2 times higher than the median of the 1st quartile of the PCB score (0.32). Table 4 shows the net effect of exposure based on the proportion of PCB 203 compared to the sum of PCBs 167 and 187. Women in the top 25 % of the PCB score had nearly three times the risk of breast cancer as women in the bottom 25 % of the PCB score. Adjustment for lipids or other breast cancer risk factors had little effect on this result (Table 4), nor did adjustment for the denominator of the PCB score or adjustment for p,p0-DDT, o,p0-DDT, and p,p0-DDE (data not shown). Figure 1 shows the actual distribution of the within-pair differences for the PCB score for cases versus controls in this study sample. In the majority of case–control pairs (62 %), the PCB score was higher among the woman who subsequently developed breast cancer. Pairs where the case had a higher PCB score also showed greater differences on the PCB score than pairs where the control had a higher score (seen in Fig. 1; compare the right side of the Y-axis (center axis) which shows pairs where cases within the pair had a higher PCB score to the left side of the Y-axis which shows pairs where controls had a higher PCB score). Fig- ure 1 is consistent with the modeling results shown in Tables 2, 3 and 4. Discussion The net effect of PCB exposure in this study population was nearly a threefold increase in breast cancer risk among women who had a higher proportion of PCB 203 in relation to the sum of PCB 167 and PCB 187 (75th percentile vs. 25th percentile). These results are novel, but not incon- sistent with the prior literature on PCBs and breast cancer. Three comprehensive reviews concluded previously that human studies of PCBs and breast cancer, which measured exposure in midlife, had variable ﬁndings [6–8]. Most prior studies reported primarily on total PCBs, which are largely determined by the PCBs found in highest concentration in humans (PCB 153, PCB 138, PCB 118, and PCB 180). We too found no associations for total PCBs, high 123