Prognostic ability of EndoPredict compared to research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study

Miguel Martin, Jan C Brase, Amparo Ruiz, Aleix Prat, Ralf Kronenwett, Lourdes Calvo, Christoph Petry, Philip S Bernard, Manuel Ruiz-Borrego, Karsten E Weber, César A Rodriguez, Isabel M Alvarez, Miguel A Segui, Charles M Perou, Maribel Casas, Eva Carrasco, Rosalía Caballero, Alvaro Rodriguez-Lescure, Miguel Martin, Jan C Brase, Amparo Ruiz, Aleix Prat, Ralf Kronenwett, Lourdes Calvo, Christoph Petry, Philip S Bernard, Manuel Ruiz-Borrego, Karsten E Weber, César A Rodriguez, Isabel M Alvarez, Miguel A Segui, Charles M Perou, Maribel Casas, Eva Carrasco, Rosalía Caballero, Alvaro Rodriguez-Lescure

Abstract

There are several prognostic multigene-based tests for managing breast cancer (BC), but limited data comparing them in the same cohort. We compared the prognostic performance of the EndoPredict (EP) test (standardized for pathology laboratory) with the research-based PAM50 non-standardized qRT-PCR assay in node-positive estrogen receptor-positive (ER+) and HER2-negative (HER2-) BC patients receiving adjuvant chemotherapy followed by endocrine therapy (ET) in the GEICAM/9906 trial. EP and PAM50 risk of recurrence (ROR) scores [based on subtype (ROR-S) and on subtype and proliferation (ROR-P)] were compared in 536 ER+/HER2- patients. Scores combined with clinical information were evaluated: ROR-T (ROR-S, tumor size), ROR-PT (ROR-P, tumor size), and EPclin (EP, tumor size, nodal status). Patients were assigned to risk-categories according to prespecified cutoffs. Distant metastasis-free survival (MFS) was analyzed by Kaplan-Meier. ROR-S, ROR-P, and EP scores identified a low-risk group with a relative better outcome (10-year MFS: ROR-S 87 %; ROR-P 89 %; EP 93 %). There was no significant difference between tests. Predictors including clinical information showed superior prognostic performance compared to molecular scores alone (10-year MFS, low-risk group: ROR-T 88 %; ROR-PT 92 %; EPclin 100 %). The EPclin-based risk stratification achieved a significantly improved prediction of MFS compared to ROR-T, but not ROR-PT. All signatures added prognostic information to common clinical parameters. EPclin provided independent prognostic information beyond ROR-T and ROR-PT. ROR and EP can reliably predict risk of distant metastasis in node-positive ER+/HER2- BC patients treated with chemotherapy and ET. Addition of clinical parameters into risk scores improves their prognostic ability.

Keywords: Breast cancer; Chemotherapy; EndoPredict; PAM50; Prognosis.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curve for metastasis-free survival by EP, ROR-S, ROR-P, EPclin, ROR-T, and ROR-PT risk groups. PAM50 ROR-S, ROR-P, and ROR-T and ROR-PT scores stratify patients (GEICAM/9906, N = 536) in low-risk, intermediate-risk and high-risk. EP and EPclin stratify patients as low-risk for distant recurrence and high-risk groups. Numbers in parentheses indicate the 95 % confidence interval of the hazard ratio. EP EndoPredict score, EPclin EP based on tumor size and nodal status, ROR risk of distant recurrence, ROR-S ROR based on subtype, ROR-P ROR based on subtype and proliferation, ROR-T ROR based on subtype and tumor size, ROR-PT ROR based on subtype, proliferation, and tumor size
Fig. 2
Fig. 2
Kaplan–Meier curves for metastasis-free survival by discordant samples between EP and ROR scores. Kaplan–Meier curves by EP–ROR-S, EP–ROR-P, EPclin–ROR-T, and EPclin–ROR-PT. Numbers in parentheses indicate the 95 % confidence interval of the hazard ratio. EP EndoPredict score, EPclin EP based on tumor size and nodal status, ROR risk of distant recurrence, ROR-S ROR based on subtype, ROR-P ROR based on subtype and proliferation, ROR-T ROR based on subtype and tumor size, ROR-PT ROR based on subtype, proliferation, and tumor size
Fig. 3
Fig. 3
Distribution of clinical and molecular parameters c-indices. EP EndoPredict score, EPclin EP based on tumor size and nodal status, ROR risk of distant recurrence, ROR-S ROR based on subtype, ROR-P ROR based on subtype and proliferation, ROR-T ROR based on subtype and tumor size, ROR-PT ROR based on subtype, proliferation, and tumor size

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