Alcohol consumption and risk of breast cancer by molecular subtype: prospective analysis of the Nurses’ Health Study after 26 years of follow-up

Abstract

Alcohol consumption is a consistent risk factor for breast cancer, although it is unclear whether the association varies by breast cancer molecular subtype. We investigated associations between cumulative average alcohol intake and risk of breast cancer by molecular subtype among 105,972 women in the prospective Nurses’ Health Study (NHS) cohort, followed from 1980 to 2006. 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. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Competing risk analyses were used to assess heterogeneity by subtype. We observed suggestive heterogeneity in associations between alcohol and breast cancer by subtype (p _het =0.06). Alcohol consumers had an increased risk of luminal A breast cancers (n=1,628 cases, per 10g/day increment HR (95%CI) =1.10(1.05–1.15)), and an increased risk that was suggestively stronger for HER2-type breast cancer (n=160 cases, HR (95%CI) =1.16(1.02–1.33)). We did not observe statistically significant associations between alcohol and risk of luminal B (n=631 cases, HR (95%CI) =1.08(0.99–1.16)), basal-like (n=254 cases, HR (95%CI) =0.90(0.77–1.04)), or unclassified (n=87 cases, HR (95%CI) =0.90(0.71–1.14)) breast cancer. Alcohol consumption was associated with increased risk of luminal A and HER2-type breast cancer, but not significantly associated with other subtypes. Given that estrogen receptors are expressed in luminal A but not in HER2-type tumors, our findings suggest that other mechanisms may play a role in the association between alcohol and breast cancer.