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Prognostic and predictive value of ERß1 and ERß2 in the Intergroup Exemestane Study (IES)-first results from PathIES†.
Speirs, V; Viale, G; Mousa, K; Palmieri, C; Reed, S N; Nicholas, H; Cheang, M; Jassem, J; Lønning, P E; Kalaitzaki, E; van de Velde, C J H; Rasmussen, B B; Verhoeven, D M; Shaaban, A M; Bartlett, J M S; Bliss, J M; Coombes, R C.
Afiliación
  • Speirs V; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Viale G; Department of Pathology, European Institute of Oncology and University of Milan, Milan, Italy.
  • Mousa K; Department of Surgery and Cancer, Imperial College London, London.
  • Palmieri C; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool.
  • Reed SN; Department of Surgery and Cancer, Imperial College London, London.
  • Nicholas H; Department of Surgery and Cancer, Imperial College London, London.
  • Cheang M; Institute of Cancer Research-Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, UK.
  • Jassem J; Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
  • Lønning PE; Section of Oncology, Institute of Clinical Medicine, University of Bergen, Bergen; Department of Oncology, Haukeland University Hospital, Bergen, Norway.
  • Kalaitzaki E; Institute of Cancer Research-Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, UK.
  • van de Velde CJH; Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
  • Rasmussen BB; Department of Pathology, Herlev Hospital, Herlev, Denmark.
  • Verhoeven DM; Department of Oncology, AZ Klina Hospital, Brasschaat, Belgium.
  • Shaaban AM; Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Bartlett JMS; Ontario Institute of Cancer Research, Toronto, Canada.
  • Bliss JM; Institute of Cancer Research-Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, UK.
  • Coombes RC; Department of Surgery and Cancer, Imperial College London, London. Electronic address: c.coombes@imperial.ac.uk.
Ann Oncol ; 26(9): 1890-1897, 2015 Sep.
Article en En | MEDLINE | ID: mdl-26002610
BACKGROUND: Intergroup Exemestane Study (IES) was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2-3 years from tamoxifen to exemestane. PathIES aimed to assess the potential prognostic and predictive value of ERß1 and ERß2 expression in primary tumours in order to determine benefit in the two treatment arms. PATIENTS AND METHODS: Primary tumour samples were available for 1256 patients (27% IES population). ERß1 and ERß2 expression was dichotomised at the median IHC score (high if ERß1 ≥ 191, ERß2 ≥ 164). Hazard ratios (HRs) were estimated by multivariable Cox proportional hazards models adjusting for clinicopathological factors. Treatment effects with biomarker expressions were determined by interaction tests. Analysis explored effects of markers both as a continuous variable and with dichotomised cut-offs. RESULTS: Neither ERß1 nor ERß2 were associated with disease-free survival (DFS) or overall survival (OS) in the whole cohort. In patients treated with continued tamoxifen, high ERß1 expression compared with low was associated with better DFS [HR = 0.38:95% confidence interval (CI) 0.21-0.68, P = 0.001]. DFS benefit of exemestane over tamoxifen (HR = 0.40:95% CI 0.22-0.70) was found in the low ERß1 subgroup (interaction P = 0.01). No significant difference with treatment was observed for ERß2 expression in either DFS or OS. CONCLUSION: In the PathIES population, exemestane appeared to be superior to tamoxifen among patients with low ERß1 expression but not in those with high ERß1 expression. This is the first trial of its kind to report a parameter potentially predicting benefit of an aromatase inhibitor when compared with tamoxifen and an independent validation is warranted.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tamoxifeno / Neoplasias de la Mama / Biomarcadores de Tumor / Receptor beta de Estrógeno / Androstadienos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tamoxifeno / Neoplasias de la Mama / Biomarcadores de Tumor / Receptor beta de Estrógeno / Androstadienos Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido