Agreement in risk prediction between the 21-gene recurrence score assay (Oncotype DX®) and the PAM50 breast cancer intrinsic Classifier™ in early-stage estrogen receptor-positive breast cancer

Abstract

Purpose: To compare risk assignment by PAM50 Breast Cancer Intrinsic Classifier™ and Oncotype DX_Recurrence Score (RS) in the same population.

Methods: RNA was extracted from 151 estrogen receptor (ER)+ stage I-II breast cancers and gene expression profiled using PAM50 "intrinsic" subtyping test.

Results: One hundred eight cases had complete molecular information; 103 (95%) were classified as luminal A (n = 76) or luminal B (n = 27). Ninety-two percent (n = 98) had a low (n = 59) or intermediate (n = 39) RS. Among luminal A cancers, 70% had low (n = 53) and the remainder (n = 23) had an intermediate RS. Among luminal B cancers, nine were high (33%) and 13 were intermediate (48%) by the RS. Almost all cancers with a high RS were classified as luminal B (90%, n = 9). One high RS cancer was identified as basal-like and had low ER/ESR1 and low human epidermal growth factor receptor 2 (HER2) expression by quantitative polymerase chain reaction in both assays. The majority of low RS cases were luminal A (83%, n = 53). Importantly, half of the intermediate RS cancers were re-categorized as low risk luminal A subtype by PAM50.

Conclusion: There is good agreement between the two assays for high (i.e., luminal B or RS > 31) and low (i.e., luminal B or RS < 18) prognostic risk assignment but PAM50 assigns more patients to the low risk category. About half of the intermediate RS group was reclassified as luminal A by PAM50.

Conflict of interest statement

Disclosures: Philip S. Bernard: Bioclassifier LLC (E, IP, OI); Mark T.W. Ebbert: ARUP Laboratories (E); Roy R.L. Bastien: ARUP Laboratories (E); Lajos Pusztai: Breast Cancer Research Foundation of New York (RF). The other author(s) indicated no financial relationships.

Figures

Figure 1.

Distribution of recurrence score over PAM50 intrinsic subtypes. Dashed lines mark recurrence score cut points (31). Abbreviations: HER-2, human epidermal growth factor receptor 2; RS, recurrence score.

Figure 2.

Classification of each tumor by RS and PAM50 and distribution by histologic grade. (A): Classification of 108 individual breast cancer cases by RS and PAM50 intrinsic classifier. (B): RS. (C): PAM50 intrinsic classifier. Abbreviations: HER-2, human epidermal growth factor receptor 2; RS, recurrence score.

Figure 3.

Examination of the discriminatory ability of Ki-67 for the luminal A and luminal B subtypes and RS categories. Shown are receiver operating characteristic curves examining the ability of Ki-67 to discriminate between high and low risk RS values (A), the luminal A and luminal B subtypes (B), and low and intermediate risk RS values (C).