Alcohol Consumption and Risk of Breast Cancer by Tumor Receptor Expression

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, 2,552 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.

Androgen receptor expression in normal breast tissue and subsequent breast cancer risk

“… 38 In contrast, alcohol consumption was found to be associated with the incidence of AR+ tumors. 39 Apart from a non-significant suggestive positive association with age, we found no relationships between these risk factors and AR expression levels in normal breast tissue. Prior studies have evaluated the associations between breast cancer risk factors and ER and progesterone receptor (PR) expression in normal tissue.…”

Outdoor Light at Night and Breast Cancer Incidence in the Nurses’ Health Study II

“…We have previously demonstrated a very high concordance between pathology reports and TMA ( Collins et al 2008 ). Additionally, we have shown in previous analyses that cases missing tumor marker information were not significantly different from cases with tumor marker information in terms of characteristics and accepted breast cancer risk factors ( Wang et al 2015 ).…”

Height and Body Size in Childhood, Adolescence, and Young Adulthood and Breast Cancer Risk According to Molecular Subtype in the Nurses' Health Studies

“…In brief, we obtained archived formalin-fixed paraffin-embedded tissue blocks for approximately 70% of incident primary breast cancer cases from 1976-2006. Women with available tissue blocks were similar with respect to breast cancer risk factors and tumor characteristics compared to the women without available tissue blocks (27, 29). In brief, hematoxylin and eosin sections from cases with pathology samples were reviewed to confirm the diagnosis, classify the histological type and grade of the breast cancer, and identify the area from which the TMA cores would be taken.…”