Ongoing and planned trials of hormonal therapy and trastuzumab.
Studies with human breast cancer cell lines have shown a causal association between overexpression of the HER-2/neu proto-oncogene receptor and the acquisition of resistance to tamoxifen. Some clinical studies also indicate that patients with tumors showing high HER-2 levels or high levels of the circulating ectodomain of HER-2 may have a lower response to tamoxifen compared with tumors with low HER-2 levels or low circulating ectodomain. Treatment with anti-HER-2 antibodies seems to restore tamoxifen activity in some experimental systems. However, whether anti-HER-2 therapies will increase tamoxifen action and/or reverse this putative oncogene-mediated resistance in patients with estrogen receptor-positive, hormone-dependent tumors, is unclear. We are conducting a phase II trial of a humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) in combination with tamoxifen in patients with estrogen receptor-positive metastatic breast cancer. Other prospective randomized clinical trials are needed to directly evaluate the contribution of HER-2 signaling to antiestrogen resistance in vivo.
Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA.
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BP
Nicholson
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D018734:Genes, erbB-2; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics; D000090063:Proto-Oncogene Mas; D013629:Tamoxifen / Q000008:administration & dosage*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013629:Tamoxifen; D000068878:Trastuzumab