ESR1 and breast cancer: Within the nested case-control data set, we observed a significant association between plasma estradiol and risk of breast cancer (Ptrend < 0.001), with an RR for the top (Q4) versus bottom (Q1) quartile category of 3.3 (95% confidence interval [CI] = 1.8 to 6.0) for ER+ breast cancer (Table 1).