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 cont emporary manner for early-stage invasive breast cancer, and to identify a s ubgroup 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 radia tion. The median follow-up was 8.9 years, with 446 patients followed for gr eater than or equal to 10 years. The median age was 55 years. Sixty-eight p ercent had T1 tumors and 74% were axillary-node. negative. Radiation was di rected to the breast only in 78%. Adjuvant therapy consisted of chemotherap y in 19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their asso ciation with the cumulative incidence of all second malignancies, contralat eral. breast cancer, and non-breast cancer malignancy were: age, menopausal status, race, family history, obesity, smoking, tumor size, location, hist ology, pathologic nodal status, region(s) treated with radiation, and the u se and type of adjuvant therapy. Results: One hundred seventy-six women developed a second malignancy (87 co ntralateral breast cancers at a median interval of 5.8 years, and 98 non-br east 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% a nd 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%, respective ly, for second non-breast cancer malignancies, excluding skin cancers. Pati ent age was a significant factor for contralateral breast cancer and non-br east cancer second malignancy. Young age was associated with an increased r isk of contralateral breast cancer, while older age was associated with an increased the risk of a second non-breast cancer second malignancy. A posit ive family history increased the risk of contralateral breast cancer, but n ot non-breast cancer malignancies. The risk of a contralateral. breast canc er increased as the number of affected relatives increased. Tamoxifen resul ted in a nonsignificant decrease in contralateral. breast cancer and an inc rease in non-breast cancer second malignancies. The 5-and 10-year cumulativ e 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 r egions 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 (endo metrial), and gastrointestinal malignancies (colerectal and pancreas). Conclusion: The 10-years cumulative incidence of a second cancer in this st udy was 16%. Young age and family history predicted for an increased risk o f contralateral breast cancer, and older age predicted for an increased ris k of non-breast cancer malignancy. The majority of patients treated with co nservative surgery and radiation with or without adjuvant systemic therapy will not develop a second cancer. Long-term follow-up is important to docum ent the risk and patterns of second cancer, and knowledge of this risk and the patterns will influence surveillance and prevention strategies. (C) 200 1 Elsevier Science Inc.