Overall survival (OS) in premenopausal ER+/PR+, HER2− breast cancer (BC) treated with endocrine therapy (ET) ± chemotherapy (CT): A National Cancer Database (NCDB) analysis.

519 Background: The comparative benefit of ET alone vs ET+CT in premenopausal women with stage I-III ER+/PR+, HER2- BC remains uncertain. Although Oncotype DX recurrence score (RS) guides CT use, management of premenopausal patients (pts) with low/intermediate RS remains challenging. The ongoing NRG-BR009 trial aims to clarify the relative benefit of CT but has faced accrual issues. To address this question, we evaluated OS difference by treatment among pts with N0 (n=0)/intermediate RS and N1 (n=1-3)/low-intermediate RS disease. Methods: NCDB data were analyzed for women <50 yrs with ER+/PR+, HER2−, stage I-III BC (2005-2022). Variables included tumor size, grade, nodal status (N0/N1), stage, lymphovascular invasion, Ki67, Charlson-Deyo comorbidity score (CCS), RS category (low=0-17, intermediate=18-30) and treatments (ET, CT, surgery, radiation [RT]). OS was compared between ET+CT vs ET only groups using the log-rank test. Multivariable Cox models (MVA) were conducted to identify predictors of OS. Results: Median age was 45 yrs (18-49) among 15591 enrolled pts. In N0/intermediate RS group, 3710 (42.5%) received ET+CT and 5022 (57.5%) received ET alone; 5-yr OS was 98.9% with ET+CT vs 98.7% with ET (p=0.40). In N1/low RS group, 1151 (26.2%) received ET+ CT and 3242 (73.8%) received only ET; 5-yr OS was 98.5% with ET+CT vs 98.6% with ET (p=0.85). In N1/intermediate RS, 1718 (69.7%) received ET+CT and 748 (30.3%) received only ET; 5-yr OS was 96.2% with ET+CT vs 95.0% with ET (p=0.28). On univariable analysis, ET+CT did not improve OS in the N0/intermediate RS, N1/low RS, or N1/intermediate RS groups (all p>0.05). MVA further confirmed ET+CT had no OS benefit compared to ET alone in all groups (all p>0.05, Table 1). Among N0/intermediate RS pts, grade 3 disease was associated with worse OS (p<0.05). In N1/low RS subjects, CCS=2 predicted worse OS (p<0.05). In N1/intermediate RS pts, stage III disease and lack of RT predicted worse OS (p<0.05). Conclusions: In premenopausal women with early-stage ER+/PR+, HER2- BC, ET+CT yielded similar OS to ET alone in low/intermediate RS pts. Limitations include inability to assess ovarian function suppression and invasive disease-free survival. Larger studies are needed to validate the above findings and to investigate whether CT could be safely omitted in low-intermediate risk pts. MVA for OS by RS and nodal status (HR, 95%CI). N0, intermediate RS N1, low RS N1, intermediate RS CCS (2 vs 0) 3.87 (0.52-29.00) 23.62 (4.63-120.46) 4.01 (0.43-37.77) Grade (3 vs 1) 7.39 (1.45-37.62) 2.26 (0.26-19.57) 1.64 (0.26-10.35) Stage (III vs I) 1.02 (0.21-4.99) n/a 11.77 (1.90-73.04) ET+CT vs ET 0.73 (0.33-1.62) 0.80 (0.25-2.51) 0.44 (0.14-1.35) RT (yes vs no) 1.02 (0.48-2.19) 2.89 (0.65-12.82) 0.22 (0.08-0.66)