Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial

F Penault-Llorca; F Dalenc; S Chabaud; P Cottu; D Allouache; D Cameron; J Grenier; L Venat Bouvet; A Jegannathen; M Campone; M Debled; A-C Hardy-Bessard; S Giacchetti; P Barthelemy; L Kaluzinski; A Mailliez; M-A Mouret-Reynier; E Legouffe; A Cayre; M Martinez; C Delbaldo; D Mollon-Grange; E J Macaskill; M Sephton; L Stefani; B Belgadi; M Winter; H Orfeuvre; M Lacroix-Triki; H Bonnefoi; J Bliss; J-L Canon; J Lemonnier; F Andre; T Bachelot

doi:10.1016/j.esmoop.2024.103443

Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial

ESMO Open. 2024 Apr 30;9(5):103443. doi: 10.1016/j.esmoop.2024.103443. Online ahead of print.

Authors

F Penault-Llorca¹, F Dalenc², S Chabaud³, P Cottu⁴, D Allouache⁵, D Cameron⁶, J Grenier⁷, L Venat Bouvet⁸, A Jegannathen⁹, M Campone¹⁰, M Debled¹¹, A-C Hardy-Bessard¹², S Giacchetti¹³, P Barthelemy¹⁴, L Kaluzinski¹⁵, A Mailliez¹⁶, M-A Mouret-Reynier¹⁷, E Legouffe¹⁸, A Cayre¹⁷, M Martinez¹⁹, C Delbaldo²⁰, D Mollon-Grange²¹, E J Macaskill²², M Sephton²³, L Stefani²⁴, B Belgadi²⁵, M Winter²⁶, H Orfeuvre²⁷, M Lacroix-Triki²⁸, H Bonnefoi¹¹, J Bliss²⁹, J-L Canon³⁰, J Lemonnier³¹, F Andre²⁸, T Bachelot³

Affiliations

¹ Centre de Lutte Contre le Cancer Jean Perrin, Imagerie Moléculaire et Stratégies Théranostiques, Université Clermont Auvergne, UMR 1240 INSERM-UCA, Clermont Ferrand. Electronic address: Frederique.PENAULT-LLORCA@clermont.unicancer.fr.
² Oncopole Claudius Regaud, IUCT, Toulouse.
³ Centre Léon Bérard, Lyon.
⁴ Institut Curie, Paris.
⁵ Centre François Baclesse, Caen, France.
⁶ Western General Hospital, Edinburg, UK.
⁷ Institut Sainte Catherine, Avignon.
⁸ CHU Dupuytren, Limoges, France.
⁹ Royal Stoke Hospital, Stoke-on-Trent, UK.
¹⁰ Institut de cancérologie de l'Ouest, Saint-Herblain & Angers.
¹¹ Institut Bergonié, Bordeaux.
¹² Centre CARIO-HPCA, Plérin.
¹³ APHP Hôpital Saint Louis, Paris.
¹⁴ Institut de Cancérologie Strasbourg Europe, Strasbourg.
¹⁵ Centre Hospitalier Cotentin, Cherbourg en Cotentin.
¹⁶ Centre Oscar Lambret, Lille.
¹⁷ Centre de Lutte Contre le Cancer Jean Perrin, Imagerie Moléculaire et Stratégies Théranostiques, Université Clermont Auvergne, UMR 1240 INSERM-UCA, Clermont Ferrand.
¹⁸ Centre Oncogard, Nîmes.
¹⁹ Clinique Pasteur, Toulouse.
²⁰ Hôpital Diaconesses, Paris.
²¹ Hôpital Laennec, Quimper, France.
²² Ninewells Hospital, Dundee.
²³ Musgrove Park Hospital, Taunton, UK.
²⁴ Centre Hospitalier Annecy, Pringy.
²⁵ Centre Hospitalier Montélimar, Montélimar, France.
²⁶ Weston Park Hospital, Sheffield, UK.
²⁷ Centre Hospitalier Fleyriat, Bourg-en-Bresse.
²⁸ Gustave Roussy, Villejuif, France.
²⁹ The Institute of Cancer Research, London, UK.
³⁰ Grand Hôpital de Charleroi, Charleroi, Belgium.
³¹ UNICANCER, Paris, France.

Abstract

Background: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.

Patients and methods: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics.

Results: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001).

Conclusions: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

Keywords: EndoPredict; breast cancer; endocrine therapy; prognostic biomarker; risk stratification.