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_Recur-rence 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. The Oncologist 2012;17:492-498

Signatures of breast cancer metastasis at a glance

“…PAM50 is a quantitative real-time PCR (qRT-PCR)-based assay of 50 genes; it evolved from studies that have reproducibly demonstrated the prognostic significance and predictive ability of the four intrinsic subtypes of breast cancer Chia et al, 2012;Harvell et al, 2008;Kelly et al, 2012;Martín et al, 2013;Nielsen et al, 2010;Prat et al, 2014;Sorlie et al, 2001Sorlie et al, , 2003. Prosigna stratifies breast cancer patients who have been treated with surgery and endocrine therapy into risk groups regarding disease outcome for years 5-10 post surgery and endocrine therapy, which helps to reduce overtreatment with chemotherapy in patients with good prognosis (Parker et al, 2009).…”

Molecular Testing in Breast Cancer: A Guide to Current Practices

“…98,99 Prosigna placed fewer patients into the intermediate-risk group than did Oncotype DX, potentially facilitating treatment decisions. 98,100 The assay is currently validated for postmenopausal women with HR þ , node-negative (stage I or II) or node-positive (stage II) disease. 101 Unlike some other MAAAs, Prosigna is not performed in a single, centralized laboratory, 95 but instead is performed in multiple reference laboratories, all using the same platform, probe library, and algorithms.…”

What makes a good biomarker?

“…From a purely scientific perspective there are some interesting observations about these expression profiles: firstly, although the intended clinical uses for some of the above tests seem quite similar and the gene signatures seem to have been identified in similar ways, the actual lists of genes included in the signatures show relatively little overlap (although maybe represent similar overall pathways) and the tests use rather different technical platforms (RT-PCR, microarray, NanoString) [17] ; secondly, the tests do not always identify exactly the same patients for classification as low or high risk for disease recurrence [18,19] . This could suggest that the utility of the tools derives not from a deep scientific understanding of the analytes (the genes, their relative degrees of expression and the actions of their products) nor even from a complete knowledge of the link between the underlying Clinical Validation • Sensitivity and specificity of the assay -clinical accuracy (in the intended patient population) • Assay failure rates (and reasons)…”