Alcohol Consumption and Incidence of Benign Breast Disease 1 Celia Byrne, 2 Penelope M. Webb, 3 Timothy W. Jacobs, Gloria Peiro, Stuart J. Schnitt, James L. Connolly, Walter C. Willett, and Graham A. Colditz Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School Boston, Massachusetts 02115 [C. B., P. M. W., W. C. W., G. A. C.]; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115 [T. W. J., G. P., S. J. S., J. L. C.]; and Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115 [W. C. W., G. A. C.] Abstract We evaluated whether moderate alcohol consumption is associated with increased risk of developing benign breast disease (BBD), a potential “precursor” or marker for breast cancer development. This study evaluated associations between reported alcohol consumption and BBD diagnosis among 75,826 women in the Nurses’ Health Study II. Between 1989 and 1997, 16,035 women reported a first diagnosis of BBD (317/10,000 person- years), of which 2,999 diagnoses were confirmed by tissue biopsy (59/10,000 person-years). Of the pathology specimens reviewed, 532 were nonproliferative benign breast conditions, and 932 were proliferative conditions. Person-time models provided estimates of the rate ratio (RR) and 95% confidence interval (CI). Reported recent adult consumption of alcohol was not associated with increased BBD incidence. Compared with women who did not drink alcohol, the age- and body mass index (BMI)-adjusted RRs for any reported BBD were 0.98 (95% CI, 0.95–1.02) for those who consumed <5 g/day, 0.93 (95% CI, 0.89 – 0.98) for those who consumed 5–14.9 g/day, and 0.90 (95% CI, 0.83– 0.98) for those who consumed >15 g/day. The adjusted RRs for biopsy confirmed BBD and any proliferative benign condition were similiar. However, reported alcohol consumption of >15 g/day between ages 18 and 22 years was associated with higher rates of biopsy-confirmed BBD (age- and body mass index-adjusted RR  1.14; 95% CI, 1.00 –1.30), nonproliferative BBD (RR  1.46; 95% CI, 1.09 –1.96), and any proliferative BBD (RR  1.33; 95% CI, 1.05–1.69), but not atypical hyperplasia. In this study, recent alcohol consumption was associated with slightly lower rates of reported BBD. However, greater alcohol consumption earlier in life (ages 18 –22 years) was associated with higher proliferative BBD rates, suggesting that timing of exposure may be relevant to disease incidence. Introduction Moderate intake of alcohol is associated with an increased risk of breast cancer. A meta-analysis of both case-control (28 studies) and cohort (10 studies) data found that compared with nondrinkers, risk of breast cancer increased 24% (95% CI, 4 1.15–1.34) with consumption of 2 drinks/day (1). Consistent with the meta-analysis report, a pooled analysis of six prospec- tive studies reported a 9% (95% CI, 1.04 –1.13) increase in breast cancer incidence with each 10 g of alcohol consumed per day (2). The majority of the data in these studies were from postmenopausal women. Although there was no significant difference in the effects of alcohol on breast cancer risk by menopause status in the meta-analysis, there was significant heterogeneity of effects across the studies among premeno- pausal women. An updated meta-analysis of 45 studies reported an overall monotonic but modest increase in the relative risk of breast cancer with increased alcohol consumption (3). The relative risks were slightly greater for cohort studies with shorter length of follow-up (10 years). Although it is difficult to separate the impact of early-age intake and recent intake, particularly among premenopausal women, for whom the early-age period may be fairly recent, several studies provide some data to address this issue. Among both premenopausal and postmenopausal women in a large multistate case-control study, recent alcohol consumption was associated with a 21% (95% CI, 1.09 –1.34) increase in risk of breast cancer per 13 g/day intake, whereas the same level of alcohol consumption before age 30 years was not associated (RR = 0.95; 95% CI, 0.63–1.45) with increased risk. However, this lack of an overall association with early (before age 30 years) alcohol consumption appeared to be driven by effects among postmenopausal women because among the premeno- pausal women in this study, each 13 g/day alcohol consumption before age 30 years was associated with a 34% (95% CI, 1.02–1.75) increase in breast cancer risk, whereas more recent alcohol consumption had little effect (4). With 6 years of follow-up among the predominantly premenopausal women participating in the NHS II cohort, recent intake was associated with a 23% (95% CI, 0.68 –2.21) increase in breast cancer risk (5). In evaluating intake at specific age intervals (18 –22, 23– 30, and 31– 40 years) in the NHS II, only alcohol consumption between ages 23–30 years was significantly associated with increased breast cancer incidence (5). Alcohol may affect breast cancer risk by increasing cir- culating levels of endogenous estrogens (6). In a controlled dietary study of premenopausal women, 30 g/day of ethanol increased blood levels of total and bioavailable estrogen (7). In Received 3/23/01; revised 7/9/02; accepted 8/19/02. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported by NIH Grants CA50385 and CA55075 from the National Cancer Institute. G. P. was supported by Grant FISS 95/5639 from Spain. 2 To whom requests for reprints should be addressed, at Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. E-mail: celia.byrne@channing. harvard.edu. 3 Present address: Queensland Institute of Medical Research, Brisbane, Queens- land, 4006 Australia. 4 The abbreviations used are: CI, confidence interval; BBD, benign breast disease; RR, rate ratio; BMI, body mass index; NHS, Nurse’s Health Study. 1369 Vol. 11, 1369 –1374, November 2002 Cancer Epidemiology, Biomarkers & Prevention on December 7, 2016. © 2002 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from