Study summary: The present nested case-control study was designed to investigate the associations between obesity, consumption of alcohol, and cigarette smoking on risk of second primary invasive contralateral breast cancer (i.e., new breast cancer in the other breast). Evidence concerning lifestyle factors that could influence the development of a second primary breast cancer among breast cancer survivors is limited. The study included 365 patients initially diagnosed with estrogen receptor positive (ER+) invasive breast cancer who were subsequently diagnosed with new primary contralateral invasive breast cancer, as well as 726 matched controls diagnosed with ER+ invasive breast cancer (but no subsequent contralateral breast tumors). Medical records and personal interviews were used to gather information concerning obesity at diagnosis, alcohol use, and smoking. Conditional logistic regression was used to calculate the associations between these three factors and risk of second primary contralateral breast cancer. Obesity, consumption of at least seven alcoholic beverages per week, and current cigarette smoking all were found to be associated with increased risk of contralateral breast cancer (odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.0 - 2.1 for obesity versus body mass index lower than 25 kg/m2; OR = 1.9; 95% CI = 1.1 - 3.2 for more than seven alcoholic drinks per week; and OR = 2.2; 95% CI = 1.2 - 4.0 for smoking). The combination of moderate to high alcohol consumption and current smoking appeared to act synergistically to heighten risk. Study participants who consumed seven drinks per week and were current smokers had 7.2 times the risk (95% CI = 1.9 - 26.5) of contralateral breast cancer of participants who consumed fewer than seven servings of alcoholic per week and had never smoked or were former smokers. The authors conclude that the results suggest that obesity, smoking, and alcohol consumption increase contralateral breast cancer risk, implying that breast cancer survivors can decrease this risk by reducing or avoiding these risk factors.