The association between alcohol consumption and an increased risk of breast cancer has been established. It is still unclear however, whether this relationship differs across the estrogen receptor (ER) and progesterone receptor (PR) tumors subtypes. To provide a quantitative assessment of the association between alcohol intake and the risk of ER-/PR-defined breast cancer, we conducted a meta-analysis of cohort and case-control studies. Studies were identified by a literature search of PubMed through April 20, 2007 and by searching the reference lists of relevant articles. Summarized risk estimates (REs) with 95% confidence intervals (CIs) were calculated using random-effects models. The summarized results of the meta-analysis comparing the highest versus the lowest consumption categories showed statistically significant higher risks of developing all ER1 (27%), all ER2 (14%), ER1PR1 (22%) and ER1PR2 (28%), but not ER2PR2 tumors. The dose-response meta-analysis showed that an increase in alcohol consumption of 10 g of ethanol per day was associated with statistically significant increased risks for all ER1 (12%), all ER2 (7%), ER1PR1 (11%) and ER1PR2 (15%), but not ER2PR2. A statistically significant heterogeneity of the REs across all ER1 versus ER2PR2 was observed (p heterogeneity 5 0.02). The summarized results from studies with adjustment for postmenopausal hormone use, body mass index and family history of breast cancer were higher and statistically significantly different from those without. The observed positive associations with alcohol for ER1PR1 and ER1PR2 tumors cannot be explained by estrogen-dependent pathway only. Further studies need to clarify the biological mechanisms. ' 2007 Wiley-Liss, Inc.Key words: breast cancer; alcohol intake; estrogen receptor; progesterone receptor; risk Considerable evidence from epidemiologic studies supports a positive association between alcohol consumption and an increased risk of breast cancer.1-3 Several previous experimental studies have shown that alcohol may stimulate the proliferation of breast tumors through modulating levels of estrogen [4][5][6] and/or that of estrogen receptors (ER).7,8 A number of hormone-independent mechanisms have also been proposed including the induction of carcinogenesis and mutagenesis by acetaldehyde [9][10][11] and by reactive oxygen species, 12 and the alteration of DNA methylation patterns by alcohol intake affecting folate metabolism. 13 It is currently unclear whether a major underlying biological mechanism of alcohol intake on the development of breast cancer is hormone-dependent or not. Four cohort studies 14-17 and 16 case-control studies [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] have reported the association between alcohol intake and ER-and/or PR-defined breast cancer risk. Majority of them was described in a qualitative literature review.34 A recent cohort study 17 reported the summarized risk estimates for a number of publications. 14,16,17,[21][22][23][25][26][27]33 However, some prior publication...