TY - JOUR
T1 - Biological therapy of breast cancer
AU - Park, John W.
AU - Tripathy, Debasish
AU - Campbell, Michael J.
AU - Esserman, Laura J.
N1 - Funding Information:
This work was supported in part by grants from the National Cancer Institute Specialized Programs of Research Excellence (SPORE) in Breast Cancer (P50-CA 58207-01), the Department of Defence Breast Cancer Research Program (DAMD17-94-J-4195), the American Society of Clinical Oncology Young Investigator Award (J.W.P.) sponsored by the Don Shula Foundation, and the Breast Cancer Research Foundation (New York, NY).
PY - 2000
Y1 - 2000
N2 - Breast cancer treatment has now entered a new era in which biological therapies, based on a rapidly expanding cellular and molecular understanding of breast cancer pathogenesis, have joined the standard armamentarium of surgery, radiation, chemotherapy, and hormone therapy. In 1998, the anti-HER2 humanised monoclonal antibody trastuzumab became the first biological therapy to receive US Food and Drug Administration (FDA) approval for the treatment of breast cancer, thus marking a milestone that almost certainly will be repeated with other new agents. HER2 (ErbB2) has been the focus of many therapeutic strategies because of its frequent gene amplification and overexpression in breast cancer, its role in tumourigenesis and cancer progression, and its prognostic and predictive significance in clinical studies. In preclinical studies, trastuzumab showed antiproliferative activity against HER2-overexpressing breast cancers in vitro and in tumour xenograft models. In a phase II clinical trial of 222 stage IV patients, trastuzumab was associated with an objective response rate of 15%. A randomised phase III clinical trial demonstrated that first-line chemotherapy for stage IV patients in combination with trastuzumab was significantly superior to chemotherapy alone. Chemotherapy plus trastuzumab was associated with a median time to progression of 7.2 months, versus 4.5 months for chemotherapy alone (p < 0.001), and a response rate of 45% versus 29% for chemotherapy alone (p = 0.001). Other novel therapies involving antibody targeting of HER2 are under development, including bispecific antibodies, immunotoxins, and immunoliposomes. Vaccine approaches are also under active investigation, including those directed against HER2 and mucin antigens. Gene therapy strategies under development include gene transfer of immunomodulatory genes and of anti-oncogene constructs. Other biological therapies include agents designed to induce differentiation or inhibit invasion, angiogenesis and metastasis.
AB - Breast cancer treatment has now entered a new era in which biological therapies, based on a rapidly expanding cellular and molecular understanding of breast cancer pathogenesis, have joined the standard armamentarium of surgery, radiation, chemotherapy, and hormone therapy. In 1998, the anti-HER2 humanised monoclonal antibody trastuzumab became the first biological therapy to receive US Food and Drug Administration (FDA) approval for the treatment of breast cancer, thus marking a milestone that almost certainly will be repeated with other new agents. HER2 (ErbB2) has been the focus of many therapeutic strategies because of its frequent gene amplification and overexpression in breast cancer, its role in tumourigenesis and cancer progression, and its prognostic and predictive significance in clinical studies. In preclinical studies, trastuzumab showed antiproliferative activity against HER2-overexpressing breast cancers in vitro and in tumour xenograft models. In a phase II clinical trial of 222 stage IV patients, trastuzumab was associated with an objective response rate of 15%. A randomised phase III clinical trial demonstrated that first-line chemotherapy for stage IV patients in combination with trastuzumab was significantly superior to chemotherapy alone. Chemotherapy plus trastuzumab was associated with a median time to progression of 7.2 months, versus 4.5 months for chemotherapy alone (p < 0.001), and a response rate of 45% versus 29% for chemotherapy alone (p = 0.001). Other novel therapies involving antibody targeting of HER2 are under development, including bispecific antibodies, immunotoxins, and immunoliposomes. Vaccine approaches are also under active investigation, including those directed against HER2 and mucin antigens. Gene therapy strategies under development include gene transfer of immunomodulatory genes and of anti-oncogene constructs. Other biological therapies include agents designed to induce differentiation or inhibit invasion, angiogenesis and metastasis.
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U2 - 10.2165/00063030-200014040-00003
DO - 10.2165/00063030-200014040-00003
M3 - Review article
AN - SCOPUS:0033755498
SN - 1173-8804
VL - 14
SP - 221
EP - 246
JO - BioDrugs
JF - BioDrugs
IS - 4
ER -