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

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3725-z) contains supplementary material, which is available to authorized users.

Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer

“…In addition, the PAM50 predictor outputs a risk of recurrence (ROR) score at 10 years. The ROR score based on subtype (ROR-S) and subtype and proliferation (ROR-P) were developed in a micro-array-based cohort of node-negative, untreated early breast cancer (34). In addition, we evaluated the following three signatures: proliferation score, which is the mean expression of 11 proliferation-related genes (21), VEGF/Hypoxia signature (30), which is the mean expression of 13 hypoxia-related genes, and claudin-low signature (as a continuous variable; ref.…”

Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial

“…In addition to the individual gene expression values, 10 independent continuous signature scores were extracted from the expression data for each sample: the correlation coefficients to each of the five PAM50 centroids; the ROR‐S and ROR‐P scores (10‐year recurrence risk based, respectively, on subtype and subtype plus proliferation); proliferation score (mean expression of 11 proliferation‐related genes); VEGF/Hypoxia signature (mean expression of 13 hypoxia‐related genes); and Claudin‐low score . An intrinsic molecular BC subtype (Luminal A, Luminal B, HER2‐enriched, basal‐like and normal‐like) was assigned according to a previously reported PAM50 subtype classifier, that is, for subsequent analysis, the five PAM50 correlation scores were reduced to an assigned “call” of the closest centroid.…”

Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays

“…Martin, et al, more recently evaluated patients from the same GEICAM 9906 study and compared prognostic features of EP and EPclin with a non‐commercial research version of PAM50 . However, the comparison does not represent a real‐world evaluation of the Prosigna assay, providing little value for practical decision‐making.…”