Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and mRNA Expression in Breast Tumors.

Smoking is a possible risk factor for breast cancer and has been linked to increased risk of estrogen receptor-positive (ER) disease in some epidemiologic studies. It is unknown whether smoking has quantitative effects on ER expression. We examined relationships between smoking and ER expression from tumors of 1,888 women diagnosed with invasive breast cancer from a population-based study in North Carolina. ER expression was characterized using binary (±) and continuous measures for ER protein, mRNA, and a multigene luminal score (LS) that serves as a measure of estrogen signaling in breast tumors. We used logistic and linear regression models to estimate temporal and dose-dependent associations between smoking and ER measures. The odds of ER, , and LS tumors among current smokers (at the time of diagnosis), those who smoked 20 or more years, and those who smoked within 5 years of diagnosis were nearly double those of nonsmokers. Quantitative levels of were highest among current smokers compared with never smokers overall [mean (log) = 9.2 vs. 8.7, < 0.05] and among ER cases; however, we did not observe associations between smoking measures and continuous ER protein expression. In relationship to breast cancer diagnosis, recent smoking was associated with higher odds of the ER, , and LS subtype. Current smoking was associated with elevated mRNA levels and an elevated LS, but not with altered ER protein. A multigene LS and single-gene mRNA may capture tumor changes associated with smoking. .