| Autor: |
Angela Lamarca, Juan W. Valle, Sharzad Moghadam, Salvatore Galdy, Angela Cramer, Jane Rogan, Mairéad G McNamara, Richard A Hubner |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Lamarca, A, Galdy, S, Moghadam, S, Rogan, J, Mcnamara, M, Hubner, R, Cramer, A & Valle, J 2017, ' HER-2/HER-3 pathway as a potentially-actionable target in biliary tract cancers (BTCs) : A retrospective analysis ', ESMO 2017 Congress, Madrid, Spain, 8/09/17-12/09/17 . < https://doi.org/10.1093/annonc/mdx369.108 > |
| DOI: |
10.1093/annonc/mdx369.108 |
| Popis: |
Background: Cholangiocarcinoma (CC), gallbladder cancer (GBC) and ampullary cancer (AC) (collectively BTCs) are poor-prognosis cancers. Cisplatin-gemcitabine chemotherapy is the standard treatment for patients (pts) with advanced BTC. New treatment targets are warranted; the human epidermal growth factor receptor (HER)-2 and HER-3 pathways may be potential candidates. High-quality data regarding expression and/or amplification rates in BTC are lacking.Methods: Pts diagnosed with BTC and with available paraffin-embedded archival tissue were eligible. Seventy consecutive pts were required (power 0.91; assumptions: 5% (no expression) vs. 15% (expression of interest); α-error 0.1). All pts had been previously consented for tissue storage for research purposes. The study was approved by the local BioBank Ethics Committee. Overexpression of HER-2 and HER-3 was analysed by immunohistochemistry (IHC) following standard guidelines (gastric criteria were followed for HER-2); samples with “2+; borderline” IHC expression underwent additional fluorescence in-situ hybridisation (FISH). Kaplan Meier and Cox Regression analyses were employed for survival. Logistic regression was used to identify factors associated with HER overexpression.Results: Of 167 screened pts between Jan-13 and Jul-15, 76 samples were retrieved for quality assessment; 67 were eligible with a median age of 65.6 years (range 32.9-79.3); 51.2% were female; 85.1% had ECOG performance status 0-1; all were adenocarcinomas. Primary site was GBC (n = 10, 14.9%), CC (n = 44, 65.7%; n = 26 intra-hepatic (ICC), n = 18 extra-hepatic (ECC)) and AC (n = 13, 19.4%). Stage at diagnosis: I/II (n = 21, 31.3%) or III/IV (n = 46, 68.7%). Estimated median overall survival (OS) for all pts was 15.9 months (95% CI 11.1-20.3). HER-2 overexpression was identified in 1 pt (1.5%). HER-3 overexpression was identified in 16 (23.9%): 1 pt was classified as “3+; positive” by IHC and 15 were confirmed by FISH following a “2+” expression in IHC. Neither HER-2 (p = 0.103) nor HER-3 (p = 0.087) impacted on OS. No factors related to HER-3 overexpression were identified.Conclusions: HER-3 is overexpressed in a significant subset of pts diagnosed with BTC; treatment targeting this pathway may warrant evaluation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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