Abstract Introduction: The 21-gene Breast Recurrence Score® assay was shown in SWOG 8814 to predict chemotherapy (CT) benefit for patients (pts) with N+ BC and Recurrence Score® (RS) result≥31 but not RS <18. In TAILORx, endocrine therapy was non-inferior to chemoendocrine therapy in 6,711 randomized pts with RS results 11-25 and N0 disease, although subgroup analyses suggested that pts age 50 years and younger with RS results 16-25 may derive some CT benefit. As we await the randomized RxPONDER results for RS 0-25 in N+ pts, we characterize BCSM in N+ pts diagnosed at age 50 years or younger by RS groups in the population-based SEER study of pts treated according to Recurrence Score results. Methods: Recurrence Score results were provided electronically to SEER registries per their linkage methods (Petkov npj Breast Cancer 2016). Eligible pts were diagnosed (Jan 2004 - Dec 2014) with N+ (micrometastases, 1-3 positive nodes), HR+, HER2-negative BC, and had no prior malignancy or multiple tumors. BCSM estimates by reported CT use were computed using TAILORx/RxPONDER cut-points of 11, 15, 20, and 25, and should be interpreted cautiously given known under-reporting of CT use to SEER, lack of randomization, and limited follow-up. Results: Among 2,588 eligible pts with Recurrence Score results, 417 (16%) had RS 0-10, 756 (29%) had RS 11-15, 715 (27%) had RS 16-20, 350 (14%) had RS 21-25, and 350 (14%) had RS 26-100. Median follow-up time was 41 months (interquartile range 24-65.) There was a significant association between Recurrence Score result and BCSM (p<0.0001) without and with adjustment for tumor size, grade, and reported CT use. Reported CT use and 5-year BCSM increased with increasing Recurrence Score result (Table.)Conclusions: Reported CT and 5-year BCSM in young pts with N+ BC increased with increasing Recurrence Score results in real-world clinical practice. 5-year BCSM was less than 2% in young pts with Recurrence Score result 0-25 and CT use reported as no or unknown. Pts with Recurrence Score result 26-100 have increased risk of BCSM despite high reported CT use. 5-year BCSM, by RS Group and Reported CT UseCT reported as 'No/Unknown'CT reported as 'Yes' RS GroupN (%)5-y BCSM ±SEN (%)5-y BCSM ±SE0-10295 (71%)0.0% ±0.0122 (29%)0.0% ±0.011-15471 (62%)0.5% ±0.3285 (38%)2.3% ±1.416-20368 (51%)1.3% ±0.9347 (49%)1.6% ±0.921-25119 (34%)1.6% ±1.6231 (66%)1.2% ±1.226-10049 (14%)4.4% ±4.3301 (86%)6.1% ±2.0 Citation Format: Valentina I Petkov, Allison W Kurian, Debbie M Jakubowski, Steven Shak. Breast cancer-specific mortality (BCSM) in patients age 50 years or younger with node-positive (N+) breast cancer (BC) treated based on the 21-gene assay in clinical practice [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-07-01.