title: Genomic Characterisation and Response to Trastuzumab and Paclitaxel in Advanced or Recurrent HER2-positive Endometrial Carcinoma.
abstract: Human epidermal growth factor receptor 2 (HER2) positivity is associated with a worse prognosis in endometrial cancer (EC). Trastuzumab as a single agent did not demonstrate activity in such cases but there are no reports on its combined use with taxanes. We report the outcome in patients treated simultaneously with trastuzumab and paclitaxel for advanced or recurrent HER2-positive endometrial carcinoma and compared it to their microsatellite instability (MSI) status and PIK3CA mutational profiles.
  
  
  
  Patients with advancedor recurrent endometrial carcinoma showing HER2 overexpression (2+ or 3+ immunohistochemical staining) or HER2 amplification (fluorescence in situ hybridization (FISH) HER2/chromosome 17 centromere (CEP 17) ratio >2.0) were treated with trastuzumab (8 mg/kg) and paclitaxel (90 mg/m2) every three weeks. Evaluation of the response was assessed according to the response evaluation criteria in solid tumors (RECIST) guidelines. Endometrial tumors, sampled before the beginning of trastuzumab, were genotyped for PIK3CA hot spot mutations using Sequenom iPLEX Assay technology.
  
  
  
  Two uterine serous adenocarcinomas and one grade 3 endometrioid adenocarcinoma showing HER2 positivity were treated with trastuzumab and paclitaxel. Between three and seven months of treatment, the three cases showed progressive disease. The genomic analysis of the three cases showed different mutational profiles. One case was found to have MSI and had one PIK3CA mutation. The two others showed no hot spot mutation for PIK3CA.
  
  
  
  Even associated with paclitaxel, HER2-positive endometrial carcinomas poorly responded to trastuzumab. This report underlines the low accuracy of HER2 positivity to predict response of endometrial cancer to combined targeted therapy using trastuzumab and paclitaxel.
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium martin.koskas@wanadoo.fr.|Department of Obstetrics and Gynecology, APHP Hôpital Bichat, Diderot University Paris, Paris, France.|EA 7285, UVSQ, Montigny le Bretonneux, France.
authors: Martin
authors: M
authors: Koskas
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium.|Department of Oncology, Laboratory for Translational Genetics, KU Leuven, Leuven, Belgium.|VIB, Vesalius Research Center (VRC), Leuven, Belgium.
authors: Jeroen
authors: J
authors: Depreeuw
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium.
authors: Stijn
authors: S
authors: Moens
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium.
authors: Daniela
authors: D
authors: Annibali
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium.
authors: Tine
authors: T
authors: Cuppens
authors: Department of Imaging and Pathology, Division of Translational Cell and Tissue Research, KU Leuven, University of Leuven, University Hospitals Leuven, Leuven, Belgium.
authors: Philippe
authors: P
authors: Moerman
authors: Department of Oncology, Laboratory for Translational Genetics, KU Leuven, Leuven, Belgium.|VIB, Vesalius Research Center (VRC), Leuven, Belgium.
authors: Diether
authors: D
authors: Lambrechts
authors: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium.|Center for Gynecologic Oncology Amsterdam (CGOA), Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands.
authors: Frederic
authors: F
authors: Amant
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage; D000068878:Trastuzumab / Q000008:administration & dosage
chemical_list: D000068878:Trastuzumab; D017239:Paclitaxel
keywords: Endometrial cancer; HER2 positivity; PIK3CA; paclitaxel; trastuzumab