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

Disclosures

Breast Cancer Res. 2019;21(128) 

In This Article

Results

We followed 17,435 women from 6948 families in the BCFR and kConFab with an average age at enrollment into the cohorts of 46.7 years. During the 181,062 person-years of follow-up (median 10.4, maximum 24.0 years), there were 1009 incident cases of BC with an average age at diagnosis of 56.2 years. Of the 17,435 women, 15% (n = 2602) reported currently smoking at baseline, 27% (n = 4675) reported formerly smoking, and 58% (n = 10,158) reported being never smokers. Current smokers smoked more intensely (mean cigarettes/day 15.1 vs 13.1) and for a longer period (mean duration 23.9 vs 14.5 years) than former smokers (Table 1). Overall, 49% (n = 8618) of women reported being regular drinkers of alcoholic beverages at baseline and reported consuming an average of 7.7 total alcoholic drinks/week. Compared with never smokers, current and former smokers were more likely to be regular drinkers (63% and 66%, respectively, vs 38% for never smokers) and consumed more alcoholic drinks per week (mean drinks per week 10.9 and 8.0, respectively, compared with 6.0 for never smokers).

Overall, there was no statistically significant association between smoking status and BC risk (former smokers HR 1.06, 95% CI 0.92–1.22; current smokers HR 1.02, 95% CI 0.85–1.23, compared with never smokers). We also observed no statistically significant associations between smoking status and risk of ER-positive BC (former smokers HR 0.97, 95% CI 0.77–1.21; current smokers HR 1.04, 95% CI 0.77–1.4, compared with never smokers) or risk of ER-negative BC (former smokers HR 0.95, 95% CI 0.63–1.41; current smokers HR 1.22, 95% CI 0.78–1.91, compared with never smokers) (Table 2). Figure 1 illustrates the association of being a current smoker (as compared to never smoking) by percentiles of absolute predicted 1-year BC risk. Although the overall interaction term was statistically significant (p value 0.03), the individual HRs at different percentiles of FRP were not, with HRs of 1.04 (95% CI 0.86–1.25) and 0.92 (95% CI 0.74–1.15) for women in the 90th and 10th percentile of 1-year BOADICEA risk score, respectively (Figure 1). These results were consistent for other measures of FRP we examined, including 10-year BOADICEA risk score and lifetime risk to age 80 (results not shown).

Figure 1.

Associations of current smoking compared to never smoking and breast cancer (BC) risk by percentiles of absolute predicted 1-year BC risk for overall BC, estrogen receptor-positive BC, and estrogen receptor-negative BC. Hazard ratios (HR) reflect associations for current smokers compared to never smokers and breast cancer risk by percentiles of absolute predicted 1-year breast cancer risk, as estimated by BOADICEA for overall breast cancer (panel a), estrogen-receptor positive breast cancer (panel b), and estrogen-receptor negative breast cancer (panel c). HRs are stratified by birth cohort and are adjusted for race/ethnicity, study center, education, oral contraceptive use, and body mass index

Overall, there was no statistically significant association between alcohol consumption and overall BC (relative to non-regular drinkers, HR for < 7 drinks per week 0.99, 95% CI 0.85–1.16; HR for ≥ 7 drinks per week 1.10, 95% 0.92–1.32) (Table 3). We also observed no significant associations between alcohol consumption and risk of ER-positive BC (HR for < 7 drinks per week 1.07, 95% CI 0.84–1.36; HR for ≥ 7 drinks per week 1.15, 95% 0.87–1.51, compared with non-drinkers) or ER-negative BC (HR for < 7 drinks per week 0.69, 95% CI 0.46–1.04; HR for ≥ 7 drinks per week 0.89, 95% 0.57–1.39, compared with non-drinkers). While we found that FRP did not modify the association for overall BC (interaction p value 0.19), we did find differences by ER subtype. We observed a negative multiplicative interaction by FRP for higher alcohol intake (≥ 7 drinks/week) compared with non-regular drinkers for ER-positive BC. As illustrated in Figure 2, women at the 10th (which translates to a 5-year BOADICEA of 0.15%) percentile of FRP had a 46% increased risk of ER-positive BC (HR 1.46, 95% CI 1.07–1.99), while there was no association for women in the 90th percentile (HR 1.07, 95% CI 0.80–1.44). We observed similar patterns when modeling alcohol use as a continuous variable (data not shown). These results were consistent for other measures of FRP we examined, including 10-year BOADICEA risk score and lifetime risk to age 80 (results not shown).

Figure 2.

Associations of consuming ≥ 7 alcoholic drinks per week (compared to non-regular drinkers) and breast cancer risk by percentiles of absolute predicted 1-year breast cancer risk for overall breast cancer, estrogen receptor-positive breast cancer, and estrogen receptor-negative breast cancer. Hazard ratios (HR) reflect associations for consuming ≥ 7 alcoholic drinks per week compared to non-drinkers and breast cancer risk by percentiles of absolute predicted 1-year breast cancer risk, as estimated by BOADICEA for overall breast cancer (panel a), estrogen-receptor positive breast cancer (panel b), and estrogen-receptor negative breast cancer (panel c). HRs are stratified by birth cohort and are adjusted for race/ethnicity, study center, education, oral contraceptive use, body mass index, and cigarette smoking

We found a significant three-way interaction for FRP, alcohol consumption (non-regular drinkers and regular drinkers), and cigarette smoking (current, former, never smokers) (interaction p value = 0.01). When we stratified models examining smoking and BC risk by alcohol consumption, we found no overall significant association for current or former smoking by regular and non-regular alcohol drinking (Table 4). We examined whether the association of smoking and BC is modified by FRP within strata of alcohol consumption and observed a statistically significant positive interaction with FRP for current vs never smokers for women who regularly consumed alcohol, but not for non-regular alcohol drinkers. While we found significant multiplicative interaction by FRP (p value = 0.005) for smoking status in women who also consumed alcohol, this was primarily driven by women with very high FRP (Figure 3). As illustrated in Figure 3, there was a 30% increased overall BC risk for women at the 95th percentile of FRP (5-year BOADICEA of 6.55%) who reported currently smoking at baseline and were regular drinkers (HR 1.30, 95% CI 0.99–1.71), and no association for current smokers with the same FRP, but were not regular drinkers (HR 0.94, 95% CI 0.66–1.35).

Figure 3.

Associations of current smoking compared to never smoking and breast cancer risk by percentiles of absolute predicted 1-year breast cancer risk stratified by alcohol consumption at baseline. Hazard ratios (HR) reflect associations for current smokers compared to never smokers and breast cancer risk by percentiles of absolute predicted 1-year breast cancer risk, as estimated by BOADICEA, stratified by alcohol consumption status at baseline; regular drinkers are presented in panel a and non-regular drinkers in panel b. HRs are stratified by birth cohort and are adjusted for race/ethnicity, study center, education, oral contraceptive use, and body mass index

The overall findings for smoking and alcohol consumption were similar in sensitivity analyses when limiting to only confirmed invasive BCs and excluding those with diagnosis of (non-breast) cancer prior to baseline (results not shown). The results in Table 2, Table 3, and Table 4 by ER status were also similar when we used a competing risk framework for ER censoring (results not shown). We did not observe significant associations with BC risk for smoking intensity, age at smoking initiation, and smoking duration, and there was no evidence of multiplicative interaction between any measure of FRP and any of these smoking and alcohol variables (Additional file 1: Table S1). The overall findings for smoking and alcohol were similar in models excluding BRCA1 and BRCA2 mutation carriers (Additional file 1: Table S2).

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