Two cohort studies have reported that alcohol and estrogen replacement therapy (ERT) act synergistically to increase the incidence of breast cancer. Possible interactions between alcohol consumption and family history of breast cancer or body mass index were also reported in the Iowa Women's Health Study data. In the Iowa Women's Health Study cohort, alcohol appears to be associated only with estrogen receptor-negative (ER-)/progesterone receptor-negative (PR-) breast cancers. Therefore, we investigated whether the interactions between alcohol and other risk factors differ according to ER/PR status. In January 1986, participants completed a questionnaire that included alcohol intake and other information. Through 1992, 939 breast cancer cases occurred among 37,105 postmenopausal women at risk. Cox proportional hazards regression was used to compute adjusted relative risks and to test for multiplicative interactions. Relative risks of ER+/PR+, ER+/PR-, and ER-/PR- breast cancer for women who consumed > or = 4.0 g of ethanol/day and reported ever using ERT compared to abstainers who never used ERT were 1.8, 1.3, and 2.6, respectively. Relative risks of ER+/PR+, ER+/PR-, and ER-/PR- breast cancer associated with any alcohol intake and a positive family history of breast cancer compared to abstainers with no family history of breast cancer were 1.7, 0.8, and 3.1, respectively. Relative risks of ER+/PR+, ER+/PR-, and ER-/PR- breast cancer associated with the highest quintile of body mass index and drinking > or = 4.0 g of ethanol/day compared to abstainers in the lower four-fifths of body mass index were 0.9, 1.8, and 2.0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)