Second cancers after conservative surgery and radiation for stages I-II breast cancer: identifying a subset of women at increased risk

PURPOSE: To assess the risk and patterns of second malignancy in a group of women treated with conservative surgery and radiation in a relatively contemporary manner for early-stage invasive breast cancer, and to identify a subgroup of these women at increased risk for a second cancer. METHODS AND MATERIALS: From 1978 to 1994, 1,253 women with unilateral Stage I-II breast cancer underwent wide excision, axillary dissection, and radiation. The median follow-up was 8.9 years, with 446 patients followed for >or= 10 years. The median age was 55 years. Sixty-eight percent had T1 tumors and 74% were axillary-node negative. Radiation was directed to the breast only in 78%. Adjuvant therapy consisted of chemotherapy in 19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their association with the cumulative incidence of all second malignancies, contralateral breast cancer, and non-breast cancer malignancy were: age, menopausal status, race, family history, obesity, smoking, tumor size, location, histology, pathologic nodal status, region(s) treated with radiation, and the use and type of adjuvant therapy. RESULTS: One hundred seventy-six women developed a second malignancy (87 contralateral breast cancers at a median interval of 5.8 years, and 98 non-breast cancer malignancies at a median interval of 7.2 years). Nine women had both a contralateral breast cancer and non-breast cancer second malignancy. The 5- and 10-year cumulative incidences of a second malignancy were 5% and 16% for all cancers, 3% and 7% for contralateral breast cancer, 3% and 8%, for all second non-breast cancer malignancies, and 1% and 5%, respectively, for second non-breast cancer malignancies, excluding skin cancers. Patient age was a significant factor for contralateral breast cancer and non-breast cancer second malignancy. Young age was associated with an increased risk of contralateral breast cancer, while older age was associated with an increased the risk of a second non-breast cancer second malignancy. A positive family history increased the risk of contralateral breast cancer, but not non-breast cancer malignancies. The risk of a contralateral breast cancer increased as the number of affected relatives increased. Tamoxifen resulted in a nonsignificant decrease in contralateral breast cancer and an increase in non-breast cancer second malignancies. The 5-and 10-year cumulative incidences for leukemia and lung cancer were 0.08% and 0.2%, and 0.8% and 1%, respectively. There was no significant effect of chemotherapy or the regions treated with radiation on contralateral breast cancer or non-breast cancer second malignancy. The most common types of second non-breast cancer malignancies were skin cancers, followed by gynecologic malignancies (endometrial), and gastrointestinal malignancies (colorectal and pancreas). CONCLUSION: The 10-years cumulative incidence of a second cancer in this study was 16%. Young age and family history predicted for an increased risk of contralateral breast cancer, and older age predicted for an increased risk of non-breast cancer malignancy. The majority of patients treated with conservative surgery and radiation with or without adjuvant systemic therapy will not develop a second cancer. Long-term follow-up is important to document the risk and patterns of second cancer, and knowledge of this risk and the patterns will influence surveillance and prevention strategies.