Associations of alcohol use with expression of stromal markers in benign breast biopsy samples

Abstract Background We explored the associations of alcohol consumption with expression of α-Smooth Muscle Actin (α-SMA), Tenascin-C (TNC), Fibroblast Activation Protein (FAP), Matrix Metalloproteinase-14 (MMP14), and Calcyclin (s100a6) stromal markers in benign breast biopsy samples. Methods The study included 683 cancer-free women from the Nurses’ Health Study II who had biopsy-confirmed benign breast disease (BBD). Alcohol consumption was assessed with semi-quantitative Food Frequency Questionnaires. The data on breast cancer (BCa) risk factors were obtained from biennial questionnaires. Immunofluorescence for stromal markers was performed on tissue microarrays. For each core, the % positivity was quantified by inForm v2.6.0. Generalised linear regression was used to examine associations between alcohol consumption (recent at biopsy date and cumulative average from all available questionnaires before the biopsy date) and log-transformed expression of each marker, adjusting for BCa risk factors and BBD subtype. Results In multivariate analysis, we observed a suggestive positive association of cumulative average alcohol with TNC ( β per 11 g/day = 0.59, 95% CI −0.03,1.22, p = 0.06). Alcohol consumption was not associated with α-SMA, FAP, s100a6, and MMP14. Conclusion Alcohol consumption may be associated with an increased normal stromal fibroblast activation as measured by TNC expression in histologically normal breast tissue. Future studies are warranted to confirm our findings.