Introduction: Smoking is a suspected risk factor for breast cancer and has been linked to increased risk of estrogen-receptor positive (ER+) disease in some epidemiologic studies. Cigarette smoke has also been shown to have antiestrogenic effects, leading to a potentially contradictory hypothesis that smoking would lead to decreased risk of breast tumors driven by estrogen-signaling. Binary classification of breast tumors with respect to ER may mask quantitative associations between smoking and ER expression. Methods: Using data from the Carolina Breast Cancer Study (CBCS), we examined relationships between smoking and quantitative levels of ER expression from tumors of 1,297 women with ER+ disease (i.e., ≥ 10% of tumor cells ER+ by immunohistochemical analysis). We used multinomial logistic regression to estimate associations between categorical measures of smoking and quartiles of ER protein or ESR1 mRNA expression, represented by odds ratios (OR) and 95% confidence intervals (95% CI). We also examined associations between smoking and quantitative ER levels among women with ER+ breast tumors, stratified by menopausal status. Multivariate regression models include adjustment for age, race, stage, grade, and tumor size. Results: Quantitative ESR1 was positively associated with any history of smoking (i.e., current at time of diagnosis or former smoking) (OR: 1.96 and 95% CI: 1.24 to 3.10). In addition, smoking more than 1 pack of cigarettes per day was associated with high ESR1 expression (OR: 3.19 and 95% CI: 1.29 to 7.91) as was smoking duration of > 20 years (OR: 2.08 and 95% CI: 1.16 to 3.74). Among former smokers, we observed higher ESR1 expression among those who quit 5-10 years prior to diagnosis. The magnitudes of association between smoking and quantitative levels of ESR1 expression were similar for both pre- and post-menopausal women, but were not reflected in similar association on the protein level. Conclusions: Among women with ER+ breast cancer, smoking dose and duration was positively associated with elevated ESR1 mRNA levels, regardless of menopausal status. Absence of this association for protein suggests that ESR1 RNA merits further consideration, but may suggest that ESR1 RNA more sensitively captures biological differences than ER protein expression.

Citation Format: Eboneé N. Butler, John A. Baron, Jeannette T. Bensen, Mengjie Chen, Kathleen Conway, Andrew F. Olshan, Melissa Troester. Smoking exposure and quantitative levels of estrogen-receptor expression in ER+ breast tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4264. doi:10.1158/1538-7445.AM2017-4264