Abstract 1885: Alcohol consumption and risk of breast cancer by molecular subtype

Abstract

Abstract Purpose: Alcohol consumption is a consistent risk factor for breast cancer, although it is unclear whether the risk varies by molecular subtype of breast cancer. Alcohol may influence breast cancer risk via a steroid hormone pathway, or through non-hormonal pathways, including increasing susceptibility to DNA damage. Methods: We assessed the associations between alcohol intake and risk of breast cancer by molecular subtypes among 106,045 women in the prospective Nurses’ Health Study (NHS) cohort. Cumulative average alcohol intake was calculated from semi-quantitative food frequency questionnaires collected every 2-4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6) and epidermal growth factor (EGFR) status from immunostained tumor microarrays in combination with histologic grade. Luminal A cases were ER-positive and/or PR-positive and HER2-negative and grade 1 or 2; Luminal B cases were either ER-positive and/or PR-positive and HER2-positive or ER-positive, PR-positive and HER2-negative with grade 3; HER2-type cases were ER-negative, PR-negative and HER2-positive; Basal-like cases were negative for ER and PR, and HER2 and positive for CK 5/6 and/or EGFR; Unclassified tumors lacked expression of all five markers. Cox proportional hazards models adjusted for age and breast cancer risk factors were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Competing risk analyses were used to assess heterogeneity in associations across subtype. Results: A total of 2,624 cases of invasive breast cancer were diagnosed between 1980 and 2006. Alcohol consumers had an increased risk of Luminal A (n = 1,572 cases, per 10g/day increment HR (95%CI) = 1.10(1.04-1.15)) and an increased risk that was suggestively stronger for HER2-type (n = 166 cases, HR = 1.19(1.06-1.35)) breast cancer. We did not observe statistically significant associations between alcohol and risk of Luminal B (n = 534 cases, HR = 1.06(0.97-1.15)), basal-like (n = 259 cases, HR = 0.88(0.76-1.03)), or unclassified (n = 93 cases, HR = 0.88(0.69-1.12)) breast cancer. There was significant heterogeneity in associations between alcohol and breast cancer by subtype (phet = 0.006). Conclusion: Alcohol consumption was associated with increased risk of Luminal A and HER2-type. Given that hormone receptors are positive in Luminal A and negative in HER2-type, our findings suggest that both hormonal and non-hormonal mechanisms may play a role in the association between alcohol and breast cancer. Citation Format: Kelly A. Hirko, Wendy Y. Chen, Susan E. Hankinson, Walter C. Willett, Rulla M. Tamimi, A. Heather Eliassen, for the Nurses' Health Study research group. Alcohol consumption and risk of breast cancer by molecular subtype. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1885. doi:10.1158/1538-7445.AM2015-1885