Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma.
HER2/neu
Recurrent
Trastuzumab
Treatment-resistant
Uterine serous carcinoma
Journal
Gynecologic oncology reports
ISSN: 2352-5789
Titre abrégé: Gynecol Oncol Rep
Pays: Netherlands
ID NLM: 101652231
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
06
01
2020
revised:
18
02
2020
accepted:
23
02
2020
entrez:
7
3
2020
pubmed:
7
3
2020
medline:
7
3
2020
Statut:
epublish
Résumé
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. 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. Selection of HER2/NEU negative tumor cells may represent a major mechanism of resistance to trastuzumab in USC patients.
Sections du résumé
BACKGROUND
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
METHODS
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
CONCLUSIONS
Selection of HER2/NEU negative tumor cells may represent a major mechanism of resistance to trastuzumab in USC patients.
Identifiants
pubmed: 32140533
doi: 10.1016/j.gore.2020.100554
pii: S2352-5789(20)30020-5
pii: 100554
pmc: PMC7049633
doi:
Types de publication
Case Reports
Langues
eng
Pagination
100554Subventions
Organisme : NCI NIH HHS
ID : U01 CA176067
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2020 The Author(s).
Références
Br J Cancer. 2006 Mar 13;94(5):642-6
pubmed: 16495918
Gynecol Oncol. 2010 Jan;116(1):15-20
pubmed: 19840887
J Clin Oncol. 2013 Nov 1;31(31):3997-4013
pubmed: 24101045
Mod Pathol. 2013 Dec;26(12):1605-12
pubmed: 23765245
Cancer. 2005 Oct 1;104(7):1391-7
pubmed: 16116605
Breast J. 2007 Mar-Apr;13(2):122-9
pubmed: 17319852
J Am Coll Surg. 2013 Feb;216(2):239-51
pubmed: 23141136
Mod Pathol. 2020 Jan;33(1):118-127
pubmed: 31477811
World J Clin Cases. 2019 Aug 6;7(15):1964-1977
pubmed: 31423428
Gynecol Oncol. 2009 Oct;115(1):142-153
pubmed: 19592079
Am J Clin Pathol. 2015 Oct;144(4):570-8
pubmed: 26386078
J Clin Oncol. 2018 Jul 10;36(20):2044-2051
pubmed: 29584549