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.