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Poster display session

3144 - HER-2/HER-3 pathway as a potentially-actionable target in biliary tract cancers (BTCs): a retrospective analysis


09 Sep 2017


Poster display session


Translational Research;  Hepatobiliary Cancers


Angela Lamarca


Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369


A. Lamarca1, S. Galdy1, S. Moghadam2, J. Rogan2, M.G. McNamara3, R.A. Hubner1, A. Cramer4, J.W. Valle5

Author affiliations

  • 1 Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 2 Biobank, Manchester Cancer Reseacrh Centre, University of Manchester, M20 4BX - Manchester/GB
  • 3 Medical Oncology, The University of Manchester / The Christie, M204BX - Manchester/GB
  • 4 Pathology Partnership, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 5 Medical Oncology, The University of Manchester / The Christie, Manchester/GB


Abstract 3144


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.


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.


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.


HER-3 is overexpressed in a significant subset of pts diagnosed with BTC; treatment targeting this pathway may warrant evaluation.

Clinical trial identification


Legal entity responsible for the study

MCRC Biobank


Dr Lamarca was part-funded by Pancreatic Cancer Research Fund (PCRF) Grant and Spanish Society of Medical Oncology (SEOM) Fellowship Grant. Dr Galdy was part-funded by “Clinical Unit Visit” European Society of Medical Oncology (ESMO) Fellowship.


All authors have declared no conflicts of interest.

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