Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and ESR1 mRNA Expression in Breast Tumors

Abstract

Background: 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.Methods: 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, ESR1 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.Results: The odds of ER⁺, ESR1⁺, 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 ESR1 were highest among current smokers compared with never smokers overall [mean (log₂) = 9.2 vs. 8.7, P < 0.05] and among ER⁺ cases; however, we did not observe associations between smoking measures and continuous ER protein expression.Conclusions: In relationship to breast cancer diagnosis, recent smoking was associated with higher odds of the ER⁺, ESR1⁺, and LS⁺ subtype. Current smoking was associated with elevated ESR1 mRNA levels and an elevated LS, but not with altered ER protein.Impact: A multigene LS and single-gene ESR1 mRNA may capture tumor changes associated with smoking. Cancer Epidemiol Biomarkers Prev; 27(1); 67-74. ©2017 AACR.