Table 1.

Studies reporting the association between alcohol intake and mammographic density

Study	Study Population	Years Recruited	Age (years)	Total, n	Prevalence of Exposure	Results: Main Effectsa	Adjustments
BI-RADS DENSITY
Jeon et al. 2011 [48]	Mammography Screening (Korea)	2008	40-80 mean 50.6	516	30% current/past users	Outcome: BI-RADS (III/IV versus I/II) Versus never users:  current/past users OR 1.36, 95% CI 0.87- 2.14	age, BMI, menopausal status, age at menarche, parity, family history, OC use, education
Yaghjyan et al. 2012 [47]	Fernald Community Cohortb (USA)	1990-2008	mean 51.3	1125	21% ever users	Outcome: BI-RADS (IV versus I) Versus never users:  users OR 2.0, 95% CI 1.4-2.8	age at mammogram, BMI at mammogram, menopausal status, age at menarche, age at first birth, parity, family history, smoking,
CONTINUOUS MEASURE OF DENSITY
Boyd et al. 1995 [49]	Hospital based sample of pre- menopausal women (Canada)	not available	29-51 mean 43.0	273	not available	Outcome: Percent Density Positive correlation between mammographic density and alcohol consumption in grams (ß (SE) 2.34 (0.81), P=0.004).	BMI, skinfolds, parity, Apo B, malondialdehyde
Cabanes et al. 2011 [53]	Spanish breast cancer screening program network (Spain)	2007-2008	45-68	3568	63% ever users 58% current users 17% consume >10 grams/day	Outcome: Percent Density (ordinal scale: <10%, 10-25%, 25-50%, 50-75%, >75%) Versus non-current users:  users OR 1.13, 95% CI 0.99-1.28  <10 g/day OR 1.11, 95% CI 0.97-1.27  ≥10 g/day OR 1.18, 95% CI 0.99-1.41 Versus never users:  former drinker OR 0.98, 95% CI 0.73-1.32  current user OR 1.13, 95% CI 0.99-1.28 Versus alcohol initiation after menarche:  before/at menarche OR 0.66, 95% CI 0.42-1.03	age at mammogram, BMI, menopausal status, parity, HRT use, smoking, screening program
Vachon et al. 2000 [51]	All studies include women from the Minnesota breast cancer family registry (US)c	1944-2001	40-90 mean 61.4	1508	mean 4 g/day	Outcome: Percent Density (visual estimation)d Among Premenopausal users (mean density):  Non-current users 39%, 95% CI 34-43  ≤3.9 g/day 45%, 95% CI 40-50  >3.9 g/day 42%, 95% CI 38-46  Ptrend=0.08 Among Postmenopausal users (mean density):  Non-current users 31%, 95% CI 26-30  ≤3.9 g/day 32%, 95% CI 27-31  >3.9 g/day 33%, 95% CI 28-31  Ptrend=0.09 Among red wine users, there was no effect among premenopausal women (Ptrend=0.42), but an inverse association among postmenopausal women (Ptrend=0.02) Among white wine users, there was no effect among premenopausal women (Ptrend=0.62), but a positive association among postmenopausal women (Ptrend<0.01)	age, age2, BMI, WHR, age at menarche, age at first birth and parity combined, family history, OC use (premenopausal only), HRT use (postme- nopausal only), smoking, physical activity, caloric intake; beer, red wine, white wine, and liquor mutually adjusted
2005 [55]			mean 60.4 at mammogram	1893	21% users before age 18 86% adult users	Outcome: Percent Density (computer assisted)d Use before age 18 (adolescent alcohol use):  Never users 21.2, 95% CI 20.8-21.7  Ever users 21.0, 95% CI 20.1-21.9  ≤6 times/year 20.2, 95% CI 18.9-21.4  >6 times/year 22.0, 95% CI 20.7-23.3 Among daily/weekly adult users (mean density):  adolescent non-users or ≤6 times/year 23.2%,  95% CI 22.2-24.2  adolescent >6 times/year 25%, 95% CI 23-27  Ptrend=0.24	age, BMI, age at menarche, age at first birth and parity, smoking, OC use, education, HRT use, menopausal status, adolescent and adult smoking; correlated frailty score based on kinship; frequency of adult alcohol use (where appropriate)
Gapstur et al. 2003 [45]	Chicago Breast Health Project, Hispanic women (US)	2000-2002	40-76	296	17% users	Outcome: Percent Density (computer assisted) Univariate associations (mean density):  Non-users 17.4%  <1 drink/week 17.8%  ≥1 drinks/week 22.2%  P=0.27	age, BMI menopausal status, age at menopause, age at menarche, age at first birth, parity, family history, HRT use, smoking, education
Maskarinec et al. 2006 [54]	The Multiethnic Cohort (MEC), Caucasian, Japanese, and Hawaiian women (US)	1993-1996	mean 57.3	1250	mean 2.3 drinks/week	Outcome: Percent Density (computer assisted) mean density:  Non-users 33.1%  <1 drink/day 34.6%  ≥1 drink/day 33.8%  Ptrend=0.96	age, BMI, menopausal status, age at menarche, age at birth, parity, family history, HRT use, case or experimental group status, ethnicity
	Breast, Estrogens, and Nutrition (BEAN) Study (US)	2000-2001	mean 43.0	217	mean 2.0 drinks/week	Outcome: Percent Density (computer assisted) mean density:  Non-users 44.5%  <1 drink/day 45.3%  ≥1 drink/day 46.1%  Ptrend=0.22	MEC matched on ethnicity and 5-year age intervals
Flom et al. 2009 [52]	New York Women’s Birth Cohort, non- Hispanic white, non-Hispanic Black, and Hispanic womene (US)	1959-1963	mean 42.4 at mammogram	151	53% current users 71% ever users	Outcome: Percent Density and Absolute Dense Area (computer assisted)f Versus non-current users:  1-6 drinks/week ß −0.09, 95% CI −4.79-4.60  ≥7 drinks/week ß 12.32, 95% CI 4.28-20.36 Versus never users:  ≤4 g/day ß 3.88, 95% CI −1.82-9.58  >4 g/day ß −0.40, 95% CI −6.07-5.27 Versus non-current red wine users:  Inverse association during the following age  periods (years): ≤20, 20-29, 30-39, 40-49	age, BMI; beer, red wine, white wine, and liquor mutually adjusted
Qureshi et al. 2012 [46]	Norwegian Breast Cancer Screening Program among postmenopausal women (Norway)	2004	50-69 mean 58.4	2251	87% current users	Outcome: Percent Density and Absolute Dense Area (computer assisted)f mean percent density:  Non-users 18.3%, 95% CI 17.3-19.6  1-<7 g/week 18.3%, 95% CI 17.5-19.3  7-14 g/week 18.3%, 95% CI 17.6-19.0  15-30 g/week 18.2%, 95% CI 17.6-18.8  31-60 g/week 18.2%, 95% CI 17.5-18.8  61-90 g/week 18.2%, 95% CI 17.2-18.9  >90 g/week 18.2%, 95% CI 16.9-19.0  Ptrend=0.91 No effect on density by alcohol type (beer, red wine, white wine, or liquor)	age at mammogram, BMI, age at menarche, age at first birth, parity, HRT use, education; beer, red wine, white wine, and liquor mutually adjusted

Abbreviations: BMI, body mass index; BI-RADS, Breast Imaging-Reporting and Data System; CI, confidence interval; g, grams; HRT, hormone replacement therapy; OC, oral contraceptive; OR, odds ratio; US, United States

^aMeasures of mammographic density: BI-RADS, four categories from the least dense to most dense: almost entirely fat (category I), scattered fibroglandular densities (category II), heterogeneously dense (category III), and extremely dense (category VI); Semi-quantitative Boyd’s scale, six categories from the least dense to most dense: 0% (A), <10% (B), 10-25% (C), 25-50% (D), 50-75% (E), and >75% (F) [38]; Percent density, defined as the percentage of dense tissue; absolute density, defined as the total dense area in cm².

^bThe Fernald Medical Monitoring Program (FMMP) was a community based surveillance program for residents living in close proximity to the former uranium processing plant in Fernald, Ohio. Women who were exposed to uranium/radiation were not eligible for the study.

^cThe Minnesota Breast Cancer Family registry recruited women from 1944-1952 and from 1990-1996 information for enrolled families were updated. From 2001-2006, a questionnaire was sent to update cancer and new exposure data. Another report was published from this cohort in the same year and found similar results and is referred to in the text [50].

^dVisual density estimation was done by trained radiologists. Training included a quantitative estimation of phantom mammograms of known densities. Other percent density measurements employed a computer assisted quantitative program.

^eThe New York Women’s Birth Cohort is an adult follow-up study of women enrolled in the National Collaborative Perinatal Project (NCPP). The adult follow-up was from 2001-2006.

^fOnly displaying results for percent density. There are no differences in inferences with absolute density.