Purpose: To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrineresponsive breast cancer patients.Experimental Design: The PAM50 assay was performed on formalin-fixed paraffin-embedded wholetumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters.Results: PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: DLRc 2 15.32, P < 0.001; ROR-based risk groups: DLRc 2 14.83, P < 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease. Conclusion: PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors. Clin Cancer Res; 20(5); 1298-305. Ó2014 AACR.
Inter-test concordance between the MammaPrint and the EndoPredict tests used to predict the risk of recurrence in breast cancer was evaluated in 94 oestrogen receptor-positive, HER2-negative breast cancers. We correlated histopathological data with clinical risk estimation as defined in the MINDACT trial. 42.6% (40/94) of cases were high-risk by MammaPrint, 44.7% (42/94) by EndoPredict (EPclin), and 45.7% (43/94) by clinical risk definition. Thirty-six percent of genomic risk predictions were discordant with a low inter-test correlation between EndoPredict and MammaPrint (
p
= 0.012; κ = 0.27, 95% CI [0.069, 0.46]). Clinical risk stratification did not correlate with MammaPrint (
p
= 0.476) but highly correlated with EndoPredict (
p
< 0.001). Consequently, clinically high-risk tumours (
n
= 43) were more frequently high-risk by EndoPredict than by MammaPrint (76.6% vs. 46.5%,
p
= 0.004), with 44% of cases discordantly classified and no significant association between genomic risk predictions (
p
= 0.294). Clinicians need to be aware that clinical pre-stratification can profoundly influence multigenomic test performance.
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