Real-world chemotherapy decision pathways and survival in early HR+/HER2- breast cancer: Oncotype DX recurrence score–guided versus clinician-guided treatment in NCDB (2010–2022).

e12754 Background: Despite widespread adoption of the 21-gene Recurrence Score (Oncotype DX RS) to guide adjuvant chemotherapy in early-stage HR+/HER2- breast cancer, real-world practice shows substantial chemotherapy use without genomic testing, relying on clinician judgment and clinicopathologic features. Prior studies show RS identifies low-risk patients who can safely omit chemotherapy, but comparative survival among chemotherapy-treated patients by RS-guided vs clinician-guided decisions remains underexplored. Methods: Using NCDB (2010–2022), we identified adult women with resected T1b–T2 N0 HR+/HER2- breast cancer who received adjuvant chemotherapy and endocrine therapy (excluding neoadjuvant therapy or missing key data). RS-guided chemotherapy (RS-CT) was defined as chemotherapy with RS > 26, and clinician-guided chemotherapy (Clin-CT) as chemotherapy based on clinician judgment without a documented RS record. Baseline differences were assessed by standardized mean differences (SMD). Overall survival (OS) was evaluated with Kaplan–Meier and stabilized inverse probability of treatment weighting (IPTW) with weighted Cox models. Absolute differences were quantified using IPCW-restricted mean survival time (RMST). Results: Among 59,247 patients (median follow-up 75.0 months), 28,349 (47.9%) were RS-guided and 30,898 (52.1%) were clinician-guided. IPTW achieved balance (post-weighting SMD < 0.10). RS-CT was associated with improved OS (adjusted HR: 0.927, 95% CI 0.878–0.979; p = 0.006). Benefit was observed in patients > 55 years among RS-CT group (HR: 0.870, 95% CI 0.816–0.928, p < 0.001; RMST +2.640 months), whereas the association was attenuated in those < 55 years (HR: 1.133, 95% CI 1.023–1.254, p = 0.016). By race, a significant benefit was seen only in Black patients (HR: 0.821, 95% CI 0.706–0.956; p = 0.011; RMST +3.554 months). Similar patterns of better survival in RS-CT group were observed across subgroups defined by T stage (lower T stage) and histologic grade (higher grade). Conclusions: In chemotherapy-treated early HR+/HER2- breast cancer, RS-guided selection was associated with superior survival vs clinician-guided decisions, with greater benefit in patients > 55 years and Black patients. These findings suggest that reliance solely on clinicopathologic features for chemotherapy decisions may not optimally identify biologic risk in the treated population, potentially exposing patients to chemotherapy toxicity without commensurate benefit, whereas the Oncotye (RS) based on genomic profiling may identify chemotherapy-eligible patients whose underlying biologic risk is not fully captured by clinicopathologic features and clinician judgment in routine practice.