Abstract
In epidemiologic studies, alcohol consumption appears more strongly associated with risk of estrogen receptor (ER)-positive than ER-negative breast cancer. However, this association has not been assessed by other potentially relevant tumor markers, such as androgen receptor (AR) or insulin receptor (IR). In the prospective Nurses' Health Study cohort, we evaluated alcohol consumption and breast cancer risk by individual tumor marker expression (i.e., ER, progesterone receptor [PR], AR, and IR) while controlling for other markers and also assessed the joint effect of these receptors. During 26 years follow-up of 106,037 women, 2552 invasive breast cancers contributed to the analysis. When all four markers were considered simultaneously, no significant heterogeneity of the alcohol and breast cancer association was observed by any of the markers. However, each increment in one drink per day was associated with 10% (95% confidence interval [CI] = 4%, 15%) and 9% (95% CI = 4%, 15%) increased risk of AR-positive and ER-positive breast cancer, respectively, while no increased risk was observed among AR-negative or ER-negative tumors. The association was independent of PR and IR expression. Assessment of the joint expression of hormone receptors revealed a significantly increased risk among AR+/ER+/PR+ (hazard ratio [HR] per drink/day = 1.11, 95% CI = 1.06, 1.17) but not in other subgroups (e.g. , AR-/ER-/PR-: HR = 0.99; 95% CI = 0.88, 1.12). Our data suggest that the alcohol and breast cancer association may be more pronounced among ER-positive and/or AR-positive breast tumors. However, our data do not support an important role of IR in the association.