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 carcinoma (MBC) will have disease involving the bony skeleton. Clonal selection mediated by parathyroid hormone‐related protein and other factors may explain the high incidence of osseous metastases in MBC. The presence of specific growth factors and cytokines in the microenvironment 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 including bone pain, pathologic fracture, hypercalcemia, and neurologic complications. MBC often is treated with systemic chemotherapy or hormonal therapy. The purpose of this article was to review the recent published literature describing the impact of systemic chemotherapy and hormonal therapy of MBC on the response of bone lesions and their clinical course and complications. Evaluating the response of bone lesions can be problematic and may be complicated by the phenomenon of "tumor flare" that may be observed with either chemotherapy or hormonal therapy. Use of the International Union Against Cancer criteria for the response of bone lesions is recommended. Several studies report objective responses (20‐60%) of lytic bone metastases to standard combination chemotherapy regimens such as cyclophosphamide, methotrexate, and 5‐fluorouracil and cyclophosphamide, doxorubicin, and 5‐fluorouracil, mitoxantrone and 5‐FU, newer combinations, and single agents including paclitaxel and docitaxel but responses to vinorelbine may be less frequent. Complete responses of bone lesions to chemotherapy are rare but partial responses and disease stabilization can lead to long term patient benefit. A series from the M. D. Anderson Cancer Center of patients with bone metastases treated with 5‐FU, doxorubicin, and cyclophosphamide chemotherapy reported a median duration of response of 14 months. In a recent multicenter study of 195 patients with lytic lesions from MBC treated with chemotherapy, the objective response rate (complete response + partial response) in bone was 18% and 65% of the patients developed at least 1 morbid skeletal event with a median onset of 7.0 months 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