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 ER beta 1 and ER beta 2 expression in primary tumours in order to determine benefit in the two treatment arms. Primary tumour samples were available for 1256 patients (27% IES population). ER beta 1 and ER beta 2 expression was dichotomised at the median IHC score (high if ER beta 1 a parts per thousand yen 191, ER beta 2 a parts per thousand yen 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. Neither ER beta 1 nor ER beta 2 were associated with disease-free survival (DFS) or overall survival (OS) in the whole cohort. In patients treated with continued tamoxifen, high ER beta 1 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 ER beta 1 subgroup (interaction P = 0.01). No significant difference with treatment was observed for ER beta 2 expression in either DFS or OS. In the PathIES population, exemestane appeared to be superior to tamoxifen among patients with low ER beta 1 expression but not in those with high ER beta 1 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.

Prognostic and predictive value of ER beta 1 and ER beta 2 in the Intergroup Exemestane Study (IES)-first results from PathIES / V. Speirs, G. Viale, K. Mousa, C. Palmieri, S.N. Reed, H. Nicholas, M. Cheang, J. Jassem, P.E. Lønning, E. Kalaitzaki, C.J.H. van de Velde, B.B. Rasmussen, D.M. Verhoeven, A.M. Shaaban, J.M.S. Bartlett, J.M. Bliss, R.C. Coombes. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 26:9(2015 Sep), pp. 1890-1897. [10.1093/annonc/mdv242]

Prognostic and predictive value of ER beta 1 and ER beta 2 in the Intergroup Exemestane Study (IES)-first results from PathIES

G. Viale
Secondo
;
2015

Abstract

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 ER beta 1 and ER beta 2 expression in primary tumours in order to determine benefit in the two treatment arms. Primary tumour samples were available for 1256 patients (27% IES population). ER beta 1 and ER beta 2 expression was dichotomised at the median IHC score (high if ER beta 1 a parts per thousand yen 191, ER beta 2 a parts per thousand yen 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. Neither ER beta 1 nor ER beta 2 were associated with disease-free survival (DFS) or overall survival (OS) in the whole cohort. In patients treated with continued tamoxifen, high ER beta 1 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 ER beta 1 subgroup (interaction P = 0.01). No significant difference with treatment was observed for ER beta 2 expression in either DFS or OS. In the PathIES population, exemestane appeared to be superior to tamoxifen among patients with low ER beta 1 expression but not in those with high ER beta 1 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.
breast cancer; oestrogen receptor beta; aromatase inhibitor; tamoxifen; prognosis; biomarker
Settore MED/08 - Anatomia Patologica
set-2015
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/313011
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