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

Silvia Pelligra; Natalia Buza; Pei Hui; Stefania Bellone; Burak Zeybek; Elena Ratner; Peter E. Schwartz; Giovanni Scambia; Alessandro D. Santin

doi:10.1016/j.gore.2020.100554

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

Silvia Pelligra, Natalia Buza, Pei Hui, Stefania Bellone, Burak Zeybek, Elena Ratner, Peter E. Schwartz, Giovanni Scambia, Alessandro D. Santin

Yale University

Risultato della ricerca: Contributo in rivista › Articolo in rivista

3 Citazioni (Scopus)

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.

Lingua originale	English
pagine (da-a)	1-4
Numero di pagine	4
Rivista	GYNECOLOGIC ONCOLOGY REPORT
Volume	32
DOI	https://doi.org/10.1016/j.gore.2020.100554
Stato di pubblicazione	Pubblicato - 2020

Keywords

HER2/neu
Recurrent
Trastuzumab
Treatment-resistant
Uterine serous carcinoma

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@article{21d2ac455f5841f9942817a788bf1212,

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

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.",

keywords = "HER2/neu, Recurrent, Trastuzumab, Treatment-resistant, Uterine serous carcinoma, HER2/neu, Recurrent, Trastuzumab, Treatment-resistant, Uterine serous carcinoma",

author = "Silvia Pelligra and Natalia Buza and Pei Hui and Stefania Bellone and Burak Zeybek and Elena Ratner and Schwartz, {Peter E.} and Giovanni Scambia and Santin, {Alessandro D.}",

year = "2020",

doi = "10.1016/j.gore.2020.100554",

language = "English",

volume = "32",

pages = "1--4",

journal = "GYNECOLOGIC ONCOLOGY REPORT",

issn = "2352-5789",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma

AU - Pelligra, Silvia

AU - Buza, Natalia

AU - Hui, Pei

AU - Bellone, Stefania

AU - Zeybek, Burak

AU - Ratner, Elena

AU - Schwartz, Peter E.

AU - Scambia, Giovanni

AU - Santin, Alessandro D.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - HER2/neu

KW - Recurrent

KW - Trastuzumab

KW - Treatment-resistant

KW - Uterine serous carcinoma

KW - HER2/neu

KW - Recurrent

KW - Trastuzumab

KW - Treatment-resistant

KW - Uterine serous carcinoma

UR - http://hdl.handle.net/10807/167378

U2 - 10.1016/j.gore.2020.100554

DO - 10.1016/j.gore.2020.100554

M3 - Article

SN - 2352-5789

VL - 32

SP - 1

EP - 4

JO - GYNECOLOGIC ONCOLOGY REPORT

JF - GYNECOLOGIC ONCOLOGY REPORT

ER -

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

Abstract

Keywords

OSS delle Nazioni Unite

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