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Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and


Butler, Ebonee N.; Bensen, Jeannette T.; Chen, Mengjie; Conway, Kathleen; Richardson, David B.; Sun, Xuezheng; Geradts, Joseph; Olshan, Andrew F.; & Troester, Melissa A. (2018). Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and. Cancer Epidemiology, Biomarkers & Prevention, 27(1), 67-74. PMCID: PMC5760366


Introduction: 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 time of diagnosis), those who smoked 20 or more years, and those who smoked within 5 years of diagnosis were nearly double those of non-smokers. Quantitative levels of ESR1 were highest among current smokers compared to 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 luminal score, but not with altered ER protein. Impact A multigene luminal score and single-gene ESR1 mRNA may capture tumor changes associated with smoking.


Reference Type

Journal Article

Year Published


Journal Title

Cancer Epidemiology, Biomarkers & Prevention


Butler, Ebonee N.
Bensen, Jeannette T.
Chen, Mengjie
Conway, Kathleen
Richardson, David B.
Sun, Xuezheng
Geradts, Joseph
Olshan, Andrew F.
Troester, Melissa A.