S4-5: Comparison of PAM50 Risk of Recurrence (ROR) Score with OncotypeDx and IHC4 for Predicting Residual Risk of RFS and Distant-(D)RFS after Endocrine Therapy: A TransATAC Study.

Abstract

Abstract Aim: To assess the performance of the risk of recurrence (ROR) score in predicting RFS and DRFS for postmenopausal patients with primary ER+ breast cancer treated with anastrozole or tamoxifen and compare this with the performance of Oncotype Dx and IHC4 for both N0 and N+ patients. Background: OncotypeDx Recurrence Score (RS) is used to assess RR after endocrine therapy in primary ER+ breast cancer and is valid for both tamoxifen and anastrozole (Dowsett ref). IHC4 is a 4-panel set of IHC markers (ER, PgR, HER2, Ki67) that was shown to provide as much prognostic accuracy as RS in the translational arm of the ATAC trial (TransATAC) of anastrozole versus tamoxifen alone or combined and subsequently independently validated (Cuzick et al, JCO, 2011, in press). PAM50 is 50-gene test that has been optimised to separate intrinsic disease subtypes and is used to generate a ROR score. Good correlation has been shown between the ROR and RS but no large scale comparisons of their ability to predict clinical outcome have been conducted. Methods: PAM50 analysis was conducted using NanoString technology on 125 ng RNA extracted from all 1026 samples from the TransATAC study that had at least 500ng RNA available. Nodal status was known on 986: N+, 271; N-neg 715. ROR scores were calculated and their relationship with RFS and DRFS assessed in both the N-neg and N+ categories. The prognostic value of ROR when added to standard clinical variables was assessed using the likelihood ratio chi-square. Finally, the relative accuracy of prognosis in this patient population using ROR, RS and IHC4 was evaluated by comparing the C-index for each test. Results: Results are currently being derived and will be presented in full. Discussion: This is the first large-scale clinical comparison of 2 prominent multi-gene predictors for use in FFPE material. The results will be instrumental in defining the preferred method for use in assessing residual risk of recurrence in patients treated with endocrine therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S4-5.