Risk Factors Predicting the Incidence of Second Primary Breast Cancer among Women Diagnosed with a First Primary Breast Cancer*

This study examined risk factors for development of a contralateral breast cancer among 4,660 US women diagnosed with a first primary breast cancer between 1980 and 1982. The authors believe it to be the first prospective cohort study on this topic that has employed direct patient interviews. All subjects were interviewed within 6 months of the diagnosis of their initial tumor as part of the multi-center, population-based, case-control Cancer and Steroid Hormone Study, and they were followed until the end of 1986 through the Surveillance, Epidemiology, and End Results program. Exclusive of those diagnosed during the initial 6 months after diagnosis of a first primary, 136 second primary breast cancers were identified. Proportional hazards models were used to assess the independent effects of multiple predictors. Specific risk factors evaluated included: age at diagnosis of first primary, exposure to exogenous hormones, menstrual and reproductive histories, tumor characteristics, demographic variables, and treatment modalities. The age-specific incidence rates of second primary breast cancer were higher in all age categories than are the incidence rates of breast cancer in the general population, yet the age at diagnosis of first primary breast cancer was not an important predictor of contralateral breast cancer. The risk of contralateral breast cancer was increased among cohort members who reported a personal history of benign breast biopsy (multivariable-adjusted rate ratio (RR) = 1.69, 95% confidence interval (CI) 1.13-2.53) and in those with an initial tumor that was classified as lobular carcinoma (multivariable-adjusted RR = 1.96, 95% CI 1.17-3.27). Treatment with chemotherapy for the first primary was associated with a lower risk of development of a second breast cancer (multivariable-adjusted RR = 0.56, 95% CI 0.33-0.96), while radiation therapy had little effect on the risk (multivariable-adjusted RR = 1.19, 95% CI 0.78-1.80).