Background: The Recurrence Score (RS) predicts outcome in node- and node+, ER+ pts treated with endocrine therapy and predicts chemotherapy benefit. We studied the prognostic impact of RS in node+, HR+ pts treated with adjuvant chemotherapy plus endocrine therapy in PACS01 Methods: PACS01 compared FECX6 with FECX3+ docetaxel X3(FEC-D) in 1999 pts. After a protocol amendment, HR-positive pts received 5 yrs of tam after chemo. The current study includes 530 pts from the PACS01 parent trial who were central IHC HR+ with sufficient tissue for OncotypeDX. The primary objective was to estimate the association between RS and distant recurrence free interval (DRFI). Secondary endpoints included disease free survival (DFS) and overall survival (OS). Median follow-up time was 7.7 yrs Results: Of the 530 pts, 209 (39.4%) had low RS; 159 (30.0%) intermediate RS; and 162 (30.6%) high RS. 74.2% were treated with tam. In the primary analysis, RS was a significant predictor of DRFI (HR= 4.1 for a 50 point difference, P<0.001), DFS (HR=3.3, P<0.001) and OS (HR=5.0, P<0.001). In multivariate analyses, RS provided independent prognostic information beyond clinicopathologic factors including treatment, age, tumor size & grade, number of + nodes, surgery type and Ki-67 status (P<0.001). RS was a significant predictor of DRFI, DFS, and OS in both treatment arms (P<0.001). There was no statistically significant interaction between RS and treatment arm in predicting distant recurrence (P=0.79). Conclusions: The 21-gene RS maintains significant prognostic impact in HR+, node+ pts who have received FEC or FEC-D adjuvant chemotherapy. These findings emphasize the need to target pts with high residual risk for recurrence with additional therapies to overcome unfavorable biology, potential endocrine and/or chemotherapy resistance.