Background: Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer overexpressing HER2/neu in about 30% of cases. Trastuzumab, a humanized monoclonal antibody targeting Her2/Neu, in combination with carboplatin/paclitaxel, is considered the preferred regimen for the treatment of advanced or recurrent HER2/Neu+ USC per NCCN guidelines. Case: We describe two USC patients with overexpression of HER2/neu at 2+/3+ level by immunohistochemistry and c-erbB2 gene amplification by fluorescence in situ hybridization (FISH) assay that, after an initial clinical response to trastuzumab, developed resistance/progression. Post-treatment biopsy (collected at the time of clinical progression on trastuzumab) demonstrated loss of HER2/neu overexpression in the recurrent/progressing tumor cells in both patients. Conclusion: Selection of HER2/NEU negative tumor cells may represent a major mechanism of resistance to trastuzumab in USC patients.
Pelligra, S., Buza, N., Hui, P., Bellone, S., Zeybek, B., Ratner, E., Schwartz, P. E., Scambia, G., Santin, A. D., Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma, <<GYNECOLOGIC ONCOLOGY REPORT>>, 2020; 32 (25): 1-4. [doi:10.1016/j.gore.2020.100554] [http://hdl.handle.net/10807/167378]
Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma
Pelligra, Silvia;Scambia, Giovanni;
2020
Abstract
Background: Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer overexpressing HER2/neu in about 30% of cases. Trastuzumab, a humanized monoclonal antibody targeting Her2/Neu, in combination with carboplatin/paclitaxel, is considered the preferred regimen for the treatment of advanced or recurrent HER2/Neu+ USC per NCCN guidelines. Case: We describe two USC patients with overexpression of HER2/neu at 2+/3+ level by immunohistochemistry and c-erbB2 gene amplification by fluorescence in situ hybridization (FISH) assay that, after an initial clinical response to trastuzumab, developed resistance/progression. Post-treatment biopsy (collected at the time of clinical progression on trastuzumab) demonstrated loss of HER2/neu overexpression in the recurrent/progressing tumor cells in both patients. Conclusion: Selection of HER2/NEU negative tumor cells may represent a major mechanism of resistance to trastuzumab in USC patients.
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