Clinical impact of the 21-gene recurrence score on adjuvant treatment selection in elderly patients with hormone receptor-positive, HER2-negative early breast cancer

The 21-gene recurrence score (RS) assay (Oncotype DX) has become a cornerstone for guiding adjuvant systemic therapy in early-stage hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) breast cancer. While randomized trials have established the clinical utility of RS, its real-world application in elderly patients remains controversial, particularly regarding potential age-related bias in treatment decision-making. We conducted a retrospective cohort study of 216 consecutive patients with early-stage HR+/HER2 − breast cancer who underwent curative surgery followed by Oncotype DX testing. Patients were stratified by age (elderly, ≥ 65 years; non-elderly, < 65 years). RS distribution and adjuvant treatment patterns were analyzed using both continuous and categorical RS measures. Adjuvant systemic therapy was classified into standard endocrine therapy, enhanced endocrine therapy, and intravenous chemotherapy, and age-related differences were evaluated overall and across RS categories. Elderly patients demonstrated a significantly lower median RS compared with non-elderly patients (11 vs. 15, p = 0.008), with a distinct shift toward lower RS categories (p = 0.039). However, substantial overlap in RS distributions was observed, including the presence of high RS tumors among elderly patients. In the overall cohort, adjuvant treatment patterns did not differ significantly by age (p = 0.884). When stratified by RS category, no significant age-related differences in treatment selection were observed in low- or intermediate-RS groups. Among patients with high RS, intravenous chemotherapy was administered to both elderly and non-elderly patients without a statistically significant difference (p = 0.106). Although elderly patients exhibited lower RS values overall, tumors with high genomic risk were observed across age groups. Age-related differences in adjuvant treatment selection were attenuated when treatment decisions were interpreted within RS-defined risk categories, including among patients with high RS. These findings support the continued use of genomic assays to facilitate biologically driven and individualized adjuvant treatment decision-making in elderly patients with HR+/HER2 − early breast cancer.