Meta-analysis of studies of alcohol and breast cancer with consideration of the methodological issues

Objective: To give an up-to-date assessment of the association of alcohol with female breast cancer, addressing methodological issues and shortfalls in previous overviews. Methods: Meta-analysis of studies (any language) providing original data on incidence of first primary breast cancer and alcohol. Two reviewers independently extracted data. Study quality assessed by objective criteria including degree of control for confounding; funnel plots examined for publication bias; meta-regression techniques to explore heterogeneity. Risks associated with drinking versus not drinking and dose-response not constrained through the origin estimated using random effects methods. Results: Ninety-eight unique studies were included, involving 75,728 and 60,653 cases in drinker versus non-drinker and dose-response analyses, respectively. Findings were robust to study design and analytic approaches in the meta-analyses. For studies judged high quality, controlled for appropriate confounders, excess risk associated with alcohol drinking was 22% (95% CI: 9-37%); each additional 10 g ethanol/day was associated with risk higher by 10% (95% CI: 5-15%). There was no evidence of publication bias. Risk did not differ significantly by beverage type or menopausal status. Estimated population attributable risks were 1.6 and 6.0% in USA and UK, respectively. Conclusions: Taking account of shortcomings in the study base and methodological concerns, we confirm the alcohol-breast cancer association. We compared our results to those of an individual patient data analysis, with similar findings. We conclude that the association between alcohol and breast cancer may be causal.