Abstract

BackgroundAlcohol consumption and cigarette smoking are associated with an increased risk of breast cancer (BC), but it is unclear whether these associations vary by a woman’s familial BC risk.MethodsUsing the Prospective Family Study Cohort, we evaluated associations between alcohol consumption, cigarette smoking, and BC risk. We used multivariable Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (CI). We examined whether associations were modified by familial risk profile (FRP), defined as the 1-year incidence of BC predicted by Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), a pedigree-based algorithm.ResultsWe observed 1009 incident BC cases in 17,435 women during a median follow-up of 10.4 years. We found no overall association of smoking or alcohol consumption with BC risk (current smokers compared with never smokers HR 1.02, 95% CI 0.85–1.23; consuming ≥ 7 drinks/week compared with non-regular drinkers HR 1.10, 95% CI 0.92–1.32), but we did observe differences in associations based on FRP and by estrogen receptor (ER) status. Women with lower FRP had an increased risk of ER-positive BC associated with consuming ≥ 7 drinks/week (compared to non-regular drinkers), whereas there was no association for women with higher FRP. For example, women at the 10th percentile of FRP (5-year BOADICEA = 0.15%) had an estimated HR of 1.46 (95% CI 1.07–1.99), whereas there was no association for women at the 90th percentile (5-year BOADICEA = 4.2%) (HR 1.07, 95% CI 0.80–1.44). While the associations with smoking were not modified by FRP, we observed a positive multiplicative interaction by FRP (pinteraction = 0.01) for smoking status in women who also consumed alcohol, but not in women who were non-regular drinkers.ConclusionsModerate alcohol intake was associated with increased BC risk, particularly for women with ER-positive BC, but only for those at lower predicted familial BC risk (5-year BOADICEA < 1.25). For women with a high FRP (5-year BOADICEA ≥ 6.5%) who also consumed alcohol, being a current smoker was associated with increased BC risk.

Highlights

  • Alcohol consumption and cigarette smoking are associated with an increased risk of breast cancer (BC), but it is unclear whether these associations vary by a woman’s familial BC risk

  • In a pooled analysis of 14 cohorts that stratified by amount of alcohol intake, the elevated BC risk associated with being a current smoker compared with non-current smokers was only observed for women who consumed alcohol [8]

  • We examined whether cigarette smoking and alcohol consumption were associated with BC risk in women across the spectrum of absolute familial risk, using a prospective cohort enriched for women at familial or genetic risk

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Summary

Introduction

Alcohol consumption and cigarette smoking are associated with an increased risk of breast cancer (BC), but it is unclear whether these associations vary by a woman’s familial BC risk. Alcohol consumption is an established breast cancer (BC) risk factor, with a 7–10% increase in BC risk for each standard alcoholic drink consumed daily The association between cigarette smoking and BC risk has been less consistently observed, but the current weight of evidence points to a modest association [7,8,9]. Since alcohol is an established and modest risk factor for BC, concerns of residual confounding by alcohol consumption when examining the association of smoking with BC risk have been raised [2]. In a pooled analysis of 14 cohorts that stratified by amount of alcohol intake, the elevated BC risk associated with being a current smoker compared with non-current smokers was only observed for women who consumed alcohol [8]

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