Alcohol Consumption, Cigarette Smoking, and Familial Breast Cancer Risk

Findings From the Prospective Family Study Cohort (ProF-SC)

Nur Zeinomar; Julia A. Knight; Jeanine M. Genkinger; Kelly-Anne Phillips; Mary B. Daly; Roger L. Milne; Gillian S. Dite; Rebecca D. Kehm; Yuyan Liao; Melissa C. Southey; Wendy K. Chung; Graham G. Giles; Sue-Anne McLachlan; Michael L. Friedlander; Prue C. Weideman; Gord Glendon; Stephanie Nesci; kConFab Investigators; Irene L. Andrulis; Saundra S. Buys; Esther M. John; Robert J. MacInnis; John L. Hopper; Mary Beth Terry


Breast Cancer Res. 2019;21(128) 

In This Article


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 (12 fl oz. of beer, 5 fl oz. of wine, or 1.5 fl oz. of hard liquor).[1–6] The association between cigarette smoking and BC risk has been less consistently observed, but the current weight of evidence points to a modest association.[7–9] A recent meta-analysis of 49 epidemiologic studies reported an 11% increase in BC risk for current smokers (RR 1.11, 95% CI 1.06–1.16), compared with never smokers.[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] Some evidence points more to synergy between the two risk factors. For example, 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]

The majority of epidemiological evidence has been collected from women at general population risk and has included few high-risk women; few studies have examined these modifiable factors for women across the spectrum of absolute BC risk. In the limited number of prospective studies with adequate sample size, no clear association between alcohol consumption and BC risk has been observed in BRCA1 or BRCA2 mutation carriers (for review see[10]). A recent prospective study of mutation carriers reported weak evidence of increased BC risk for current smokers compared with never smokers (HR 1.28; 95% CI 1.00–1.64).[11]

Estimates of relative risks from cohorts with large variation in absolute BC risk are important to understand associations with modifiable factors on an absolute risk scale.[12] For example, we have found that several risk factors for BC do not vary by FRP (tested as multiplicative interactions) including benign breast disease and high body mass index (BMI), which is important to highlight because it means that on an absolute level, women at higher BC risk may benefit more from the relative risk reductions.[13–16] Of the few studies that have examined interaction between BC family history and either alcohol consumption or cigarette smoking, three have suggested similar associations regardless of family history,[17–19] while others found a lack of associations with smoking or alcohol for women with primarily a first-degree BC family history.[4,20–22] These studies, however, were limited in evaluating interaction with BC family history, as only a small proportion (4–13%) of participants had a family history.[18,19,21] Additionally, most studies only examined family history as a binary construct (yes/no) and did not examine modification of risk across the spectrum of absolute BC risk. Thus, evidence from prospective cohorts with sufficient statistical power to examine the association of modifiable exposures across the spectrum is essential and an important first step in developing appropriate clinical recommendations for women across the risk spectrum, and particularly for women at the higher end of the risk spectrum who may only be given clinical advice on modifiable factors based on average risk women and/or not advised at all. 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.