Study summary: The current study was designed to determine whether the risk of breast cancer associated with hormone replacement therapy use is increased by alcohol consumption. Both alcohol and postmenopausal hormone use are well-established risk factors for breast cancer. The study included 5,035 postmenopausal women in the Copenhagen City Heart Study. The women were questioned regarding their alcohol intake and hormone use at baseline during 1981 to 1983. They were followed until 2002 in the Danish cancer registry, with lower than one percent loss to follow-up. During the follow-up period, 267 women developed invasive breast cancer. Alcohol consumption was found to be associated with a small increase in risk of breast cancer (hazard ratio = 1.11 per drink/day, 95% CI: 0.99-1.25). Women who used hormone replacement also were found to have an enhanced risk of breast cancer (HR = 2.00, 95% CI: 1.52-2.61) compared to those who did not use hormones. The study found a strong interaction between these two factors - those who consumed more than two drinks per day and also took hormones had a risk of 4.74 (95% CI: 2.61-8.59) for breast cancer compared to those who neither drank nor took hormones. Alcohol was not found to be associated with breast cancer among women who did not use hormones (HR = 0.98 per drink/day, 95% CI: 0.82-1.78).