Alcohol consumption and breast cancer risk by estrogen receptor status: in a pooled analysis of 20 studies

Abstract

Background: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts.

Methods: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model.

Results: Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status.

Conclusions: Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.

Keywords: Alcohol; breast cancer; cohort study; epidemiology; estrogen receptor; folate; pooled analyses; progesterone receptor.

Figure 1.

Multivariable relative risks (95% CIs) for 5 g/d categories of alcohol consumption and total breast cancer, compared with non-drinkers; multivariable model included the covariates listed in footnote ‘a’ in Table 2. The proportion of the study population in each category was 38% for non-drinkers, 35% for > 0–< 5 g/d, 10% for 5–< 10 g/d, 7% for 10–< 15 g/d, 4% for 15–< 20 g/d, 2% for 20–< 25 g/d, 1% for 25–< 30 g/d, 1% for 30–< 35 g/d, 1% for 35–< 40 g/d, 0.4% for 40–< 45 g/d, 0.4% for 45–< 50 g/d, 0.2% for 50–< 55 g/d, 0.1% for 55–< 60 g/d, 0.1% for 60–< 65 g /d, 0.1% for 65–< 70 g/d and 0.4% for ≥ 70 g/d. ^*RR and 95% confidence interval for the ≥ 70 g/d alcohol intake category vs non-drinkers.