Genomic risk distribution, adjuvant chemotherapy trends, and survival outcomes in women with pT1, grade 1-2, ER/PR-positive, LVI-negative breast cancer

BACKGROUND: Oncotype DX Recurrence Score (RS) guides adjuvant chemotherapy decisions in early-stage hormone receptor-positive (HR+), HER2-negative breast cancer (BC). However, the survival benefit of adjuvant chemotherapy in patients with pT1, low-grade, and low clinical risk disease remains incompletely characterized, particularly across different age groups. METHODS: This retrospective cohort study utilized the National Cancer Database (NCDB) to identify women with pT1, Grade 1-2, HR+/HER2-, lymphovascular invasion (LVI)-negative BC who underwent genomic testing (Oncotype DX or MammaPrint) and received either adjuvant endocrine therapy (ET) alone or chemoendocrine therapy (CET) between 2010-2021. The primary outcome was overall survival (OS). Kaplan-Meier survival analysis, log-rank testing, and univariable and multivariable Cox proportional hazards models were employed to compare OS between treatment groups, stratified by age (≤50 vs. >50 years), genomic risk category, and combined age-genomic risk strata. RESULTS: Among 11,411 patients analyzed, 26% received CET. In age-stratified analysis, CET was associated with improved OS only in patients >50 years (log-rank p=0.01; adjusted hazard ratio [aHR]=0.70, 95% CI 0.63-0.87) but not in those ≤50 years (p=0.73; aHR=0.90, 95% CI 0.15-1.50). When stratifying by combined age and genomic risk, CET conferred an OS advantage exclusively in patients >50 years with intermediate-risk RS (log-rank p=0.001; aHR=0.70, 95% CI 0.52-0.92) and high-risk RS (log-rank p=0.001; aHR=0.75, 95% CI 0.61-0.93). No significant OS benefit was observed with CET in patients with low genomic risk regardless of age. CONCLUSIONS: These findings support genomic risk-stratified treatment decisions in early-stage HR+/HER2- BC and suggest limited benefit of chemotherapy in the lowest-risk subgroups.