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Ongoing and planned trials of hormonal therapy and trastuzumab
1Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA.
Abstract:
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.
Insights
Overexpression of the HER-2 receptor is linked to tamoxifen resistance in breast cancer. Combining anti-HER-2 therapy with tamoxifen may overcome this resistance in patients with estrogen receptor-positive metastatic breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Overexpression of the HER-2/neu proto-oncogene receptor is causally associated with tamoxifen resistance in human breast cancer cell lines.
- Clinical studies suggest patients with high HER-2 levels exhibit lower response rates to tamoxifen.
- Anti-HER-2 antibodies have shown potential to restore tamoxifen activity in experimental models.
Purpose of the Study:
- To investigate whether anti-HER-2 therapies can enhance tamoxifen efficacy and reverse oncogene-mediated resistance.
- To evaluate the combination of trastuzumab (anti-HER-2 antibody) and tamoxifen in estrogen receptor-positive metastatic breast cancer patients.
Main Methods:
- Phase II clinical trial design.
- Administration of a humanized anti-HER-2 monoclonal antibody, trastuzumab, in combination with tamoxifen.
- Patient population: estrogen receptor-positive metastatic breast cancer.
Main Results:
- The study is currently conducting a phase II trial, results are pending.
- The abstract does not contain specific results from the trial.
Conclusions:
- The efficacy of anti-HER-2 therapies in reversing tamoxifen resistance in vivo remains unclear.
- Further prospective randomized clinical trials are necessary to confirm the role of HER-2 signaling in antiestrogen resistance.