Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma

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...

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Detalles Bibliográficos
Autores principales: Pelligra, Silvia, Buza, Natalia, Hui, Pei, Bellone, Stefania, Zeybek, Burak, Ratner, Elena, Schwartz, Peter E., Scambia, Giovanni, Santin, Alessandro D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Case Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049633/
https://www.ncbi.nlm.nih.gov/pubmed/32140533
http://dx.doi.org/10.1016/j.gore.2020.100554
Descripción
Sumario: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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