Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases

Published data meta-analysis

We identified 22 studies that investigated the relationship between alcohol consumption and survival (Table 1). Half of these studies had been conducted in the United States. Sample size varied considerably (range: 125–9,325 cases), with 12 studies including more than 1,000 cases. Median follow-up ranged from 3 to 13 years. Ten studies reported findings based on alcohol intake before breast cancer diagnosis and 12 studies measured alcohol intake after diagnosis.

Seventeen studies reported the relationship between alcohol consumption and OS. Most studies reported no significant association between pre- or postdiagnosis alcohol consumption and OS (1–10). However, some studies found a protective effect of alcohol (11–16) and one showed an adverse effect (28). We excluded six of these studies from the meta-analysis as follows. One study reported a protective effect of alcohol but provided HRs without 95% CIs and an overall P value across multiple levels of exposure (15). Another study reported no association for a comparison of drinkers with nondrinkers (3). Two studies (9, 11) modeled alcohol intake as a continuous variable, one of which used data from SEARCH that we have updated in the new analysis reported in this paper (11). The other study reported no association between alcohol intake and prognosis (9). One study was excluded because there were large overlaps with the data reported in other publications (7). Finally one study was excluded because of lack of details about levels of exposure, although a trend toward lower risk of death from any cause with higher alcohol consumption was reported (P_trend = 0.01; ref. 12).

Thus, 11 studies were included in the meta-analysis. For the purposes of this meta-analysis, we pooled the results for the reported comparison that we considered most closely approximating moderate alcohol consumption (up to 14 U per week) compared with nondrinkers. Six studies reported the association between prediagnosis alcohol intake and OS. Moderate alcohol consumption was associated with better survival (Fig. 1; HR, 0.80; 95% CI, 0.73–0.88). Five studies reported the association with postdiagnosis alcohol intake which was not associated with all-cause mortality (Fig. 2; HR, 0.95; 95% CI, 0.85–1.05).

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Figure 1.

HRs for prediagnosis alcohol consumption and overall mortality (moderate drinkers vs. nondrinkers); P_{heterogeneity} = 0.36.

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Figure 2.

HRs for postdiagnosis alcohol consumption and overall mortality (moderate drinkers vs. nondrinkers); P_{heterogeneity} = 0.12.

Of the 11 studies that reported on BCSS, six studies reported no association (1, 12, 14, 18, 20, 22) and four studies reported that increased alcohol intake was associated with increased breast cancer-specific mortality (2, 7, 19, 21). The reporting of alcohol consumption in these studies was very heterogeneous. Therefore, it was not possible to combine estimates in a formal meta-analysis. One study did not report details about levels of exposure (12), one study did not use non- or minimal drinkers as a reference group (20), and two studies modeled alcohol intake as a continuous variable (19, 21). Both of these reported that alcohol consumption was associated with a poorer prognosis, but the sample sizes were small and in one, the effect was limited to beer drinkers (19). Kwan and colleagues (7) showed that drinking ≤6 g/day of alcohol compared with no drinking was associated with an increased risk of death due to breast cancer (HR, 1.51; 95% CI, 1.00–2.29). However, in a more recent analysis with a large sample size, this association was not observed (1). One study (2) showed increased risk of death from breast cancer in drinkers especially among those who consumed 12 or more grams of alcohol per day in comparison with nondrinkers (HR, 1.74; 95% CI, 1.13–2.67). Holm and colleagues (20) showed no statistically significant association (HR, 1.06; 95% CI, 0.66–1.72), but their reference group was women who consumed one unit or less per day. Similarly, Harris and colleagues (14) showed no significant association between alcohol intake and BCSS. In that study, women who consumed 10 g per day or more of alcohol had an adjusted HR of breast cancer-specific death of 1.36 (95% CI, 0.82–2.26; P_trend: 0.47) compared with nondrinkers. Similar conclusions of null association were made by others (12, 18, 22).

Three studies examined the relationship between prediagnosis alcohol consumption and breast cancer recurrence and four examined postdiagnosis alcohol consumption; four showed no association (1, 2, 9, 13) and three showed increased risk of recurrence (7, 19, 20). Again, heterogeneity prevented the combining of these studies. Two studies modeled alcohol intake as a continuous variable (9, 19), one study did not use non- or minimal drinkers as a reference group (20) and there was an overlap between two studies (1, 7). In one of the studies (19), a statistically significant increased risk of recurrence with beer drinking (drinks/day) was reported (HR, 1.41; 95% CI, 1.02–1.97). Similarly, Kwan and colleagues (7) showed that drinking ≥ 6 g/day of alcohol compared with no drinking was associated with an increased risk of breast cancer recurrence (HR, 1.35; 95% CI, 1.00–1.83). This association has been confirmed only in postmenopausal women in their recent analysis (1); in which postmenopausal women who regularly consumed alcohol had an increased risk of recurrence (HR, 1.19; 95% CI, 1.01–1.40). Like other studies (9, 13), Holm and colleagues (20) showed no statistically significant association with moderate drinking (HR, 1.31; 95% CI, 0.81–2.11). However, they found a modest but significant association among heavy drinkers between prediagnostic alcohol consumption and recurrence, both when using baseline measures of alcohol intake (HR, 1.65; 95% CI, 1.02–2.67) and cumulated alcohol intake (HR, 2.02; 95% CI, 1.06–3.85).

SEARCH, EPIC, and BCAC

Postdiagnosis alcohol intake data were available for 8,446 patients with breast cancer in SEARCH with 55,684 person-years of follow-up (median 6 years). Age at diagnosis varied from 23 to 73 years (mean 54 years). There were 1,506 deaths of which 1,213 were due to breast cancer. The annual mortality rate was 2 per 100 and the 5-, 10-, and 15-year breast cancer survival rates were 88% (95% CI, 87%–89%), 75% (95% CI, 74%–77%), and 43% (95% CI, 36%–50%), respectively. Supplementary Table S2 shows the characteristics of the SEARCH study by postdiagnosis alcohol consumption. Alcohol intake tended to be higher for women with low-grade and early-stage tumors and varied by ER status, BMI, SES, smoking, and menopausal status.

Prediagnosis alcohol intake data were available for 10,561 patients in EPIC with 69,383 person-years of follow-up (median 7 years). Age at diagnosis varied from 25 to 93 years (mean 60 years). There were 1,422 deaths of which 749 were due to breast cancer. The 5-, 10-, and 15- year breast cancer survival rates were 90% (95% CI, 90%–91%), 81% (95% CI, 80%–82%), and 71% (95% CI, 69%–75%), respectively. Supplementary Table S3 shows the characteristics of the EPIC study by prediagnosis alcohol consumption. Alcohol consumption varied by menopausal status, BMI, and SES. There was a trend for alcohol consumption to decrease with increasing BMI. There were missing data in most of the variables studied, especially ER status (35%). Supplementary Table S4 shows the distribution of alcohol consumption by country in the EPIC cohort.

Prediagnosis alcohol intake data were available for 10,232 patients in BCAC with 69,710 person-years of follow-up (median 6 years). Age at diagnosis varied from 18 to 95 years (mean 54 years). There were 1,911 deaths of which 860 were due to breast cancer. The 5-, 10-, and 15-year breast cancer survival rates were 88% (95% CI, 87%–88%), 77% (95% CI, 76%–78%), and 66% (95% CI, 64%–67%), respectively. Supplementary Table S5 shows the characteristics of the BCAC data by study.

The associations between self-reported alcohol intake and prognosis in women with ER-positive breast cancer are shown in Table 2. There was a weak inverse association between postdiagnosis alcohol intake and all-cause mortality for women with ER-positive tumors (SEARCH data) with an apparent dose-response effect in univariate analysis. However, the association was substantially attenuated after adjustment for stage, grade, BMI, smoking status, SES, and menopausal status. There was also an inverse association between postdiagnosis alcohol intake and BCSS in ER-positive disease, but the effect was weaker than for OS and no association remained in the multivariate analysis. There was a very similar pattern for the inverse association of prediagnosis alcohol intake and both OS and BCSS in