ISSUES CONCERNING THE ROLE OF CHEMOTHERAPY AND HORMONAL-THERAPY OF BONE METASTASES FROM BREAST-CARCINOMA

A significant percentage (50-70%) of patients with metastatic breast c arcinoma (MBC) will have disease involving the bony skeleton. Clonal s election mediated by parathyroid hormone-related protein and other fac tors may explain the high incidence of osseous metastases in MBC. The presence of specific growth factors and cytokines in the microenvironm ent of bone may contribute to the successful establishment and growth of metastatic lesions and also might determine response or resistance of these lesions to chemotherapy or hormonal therapy. Osteolytic bone lesions in MBC frequently give rise to serious clinical problems inclu ding bone pain, pathologic fracture, hypercalcemia, and neurologic com plications. MBC often is treated with systemic chemotherapy or hormona l therapy. The purpose of this article was to review the recent publis hed literature describing the impact of systemic chemotherapy and horm onal therapy of MBC on the response of bone lesions and their clinical course and complications. Evaluating the responses of bone lesions ca n be problematic and may be complicated by the phenomenon of ''tumor f lare'' that may be observed with either chemotherapy or hormonal thera py. Use of the International Union Against Cancer criteria for the res ponse of bone lesions is recommended. Several studies report objective responses (20-60%) of lytic bone metastases to standard combination c hemotherapy regimens such as cyclophosphamide, methotrexate, and 5-flu orouracil and cyclophosphamide, doxorubicin, and 5-fluorouracil, mitox antrone and 5-FU, newer combinations, and single agents including pacl itaxel and docitaxel but responses to vinorelbine may be less frequent . Complete responses of bone lesions to chemotherapy are rare but part ial responses and disease stabilization can lead to long term patient benefit. A series from the M. D. Anderson Cancer Center of patients wi th bone metastases treated with 5-FU, doxorubicin, and cyclophosphamid e chemotherapy reported a median duration of response of 14 months. In a recent multicenter study of 195 patients with lytic lesions from MB C treated with chemotherapy, the objective response rate (complete res ponse + partial response) in bone was 18% and 65% of the patients deve loped at least 1 morbid skeletal event with a median onset of 7.0 mont hs from the start of chemotherapy. Hormone-dependent breast carcinoma has a proclivity to metastasize to bone. In earlier studies comparing aminoglutethimide or medroxyprogesterone acetate with tamoxifen, a hig her response rate of bone metastases was observed for the first two ag ents. However, in more recent studies comparing newer aromatase inhibi tors, such as anastrozole, fadrozole, and letrozole, with megestrol ac etate, there were no significant differences in rates of response in b one. Patients with MBC with bony lesions respond to both chemotherapy and hormonal therapy and can have a prolonged survival. Therefore such patients are in a more favorable position to benefit from adjunctive supportive therapy such as bisphosphonates intended to reduce skeletal morbidity. (C) 1997 American Cancer Society.