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Biological Therapy of Breast Cancer

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Abstract

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 differentiaio nor inhibit invasion, angiogenesis and metastasis.

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Notes

  1. Use of a trade names is for product identification purposes only, and does not imply endorsement.

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Acknowledgements

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).

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  1. Carol Franc Buck Breast Care Center, UCSF Cancer Center, San Francisco, California, USA

    John W. Park, Debasish Tripathy, Michael J. Campbell & Laura J. Esserman

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  1. John W. Park
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Correspondence to John W. Park.

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Park, J.W., Tripathy, D., Campbell, M.J. et al. Biological Therapy of Breast Cancer. BioDrugs 14, 221–246 (2000). https://doi.org/10.2165/00063030-200014040-00003

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