Issues concerning the role of chemotherapy and hormonal therapy of bone metastases from breast carcinoma

Harold Harvey

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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 lyric 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 tamoxifen, a higher response rate of bone metastases was observed for the first two agents. However, in more recent studies comparing newer aromatase inhibitors, such as anastrozole, fadrozole, and letrozole, with megestrol acetate, there were no significant differences in rates of response in bone. 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.

Original languageEnglish (US)
Pages (from-to)1646-1651
Number of pages6
JournalCancer
Volume80
Issue number8 SUPPL.
StatePublished - Oct 15 1997

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Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Drug Therapy
Fluorouracil
Therapeutics
Cyclophosphamide
letrozole
Doxorubicin
Fadrozole
Megestrol Acetate
Aminoglutethimide
Parathyroid Hormone-Related Protein
Mitoxantrone
Spontaneous Fractures
Medroxyprogesterone Acetate
Aromatase Inhibitors
Diphosphonates
Hypercalcemia
Tamoxifen

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Issues concerning the role of chemotherapy and hormonal therapy of bone metastases from breast carcinoma",
abstract = "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 lyric 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 tamoxifen, a higher response rate of bone metastases was observed for the first two agents. However, in more recent studies comparing newer aromatase inhibitors, such as anastrozole, fadrozole, and letrozole, with megestrol acetate, there were no significant differences in rates of response in bone. 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.",
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Issues concerning the role of chemotherapy and hormonal therapy of bone metastases from breast carcinoma. / Harvey, Harold.

In: Cancer, Vol. 80, No. 8 SUPPL., 15.10.1997, p. 1646-1651.

Research output: Contribution to journalArticle

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N2 - 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 lyric 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 tamoxifen, a higher response rate of bone metastases was observed for the first two agents. However, in more recent studies comparing newer aromatase inhibitors, such as anastrozole, fadrozole, and letrozole, with megestrol acetate, there were no significant differences in rates of response in bone. 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.

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