Adjuvant Radiation and Endocrine Therapy in Early-Stage Breast Cancer With Low Genomic Risk

De-escalation of adjuvant therapy is feasible for select older patients with early-stage breast cancer. It is not known whether we can expand de-escalation options for younger patients by incorporating genomic biomarkers, such as the Oncotype DX 21-gene recurrence score (ODX RS). To evaluate outcomes of radiotherapy (RT) or endocrine therapy (ET) de-escalation for patients aged 50 to 69 years with early-stage breast cancer and an ODX RS of 18 or below. This cohort study was conducted at a comprehensive cancer center among patients aged 50 to 69 years with T1N0, hormone receptor-positive, ERBB2-negative breast cancer, with an ODX RS of 18 or below. Patients were treated between January 2007 and January 2023 with lumpectomy and ET, with or without adjuvant RT. Patients were considered adherent to ET if they received 5 years of ET or more, or if it was ongoing at last follow-up; nonadherence included halting ET within 5 years after initiation. Cumulative incidence of locoregional recurrence (LRR) was the primary end point, with death and non-local-regional events as competing risks. This analysis included 2249 patients (median [IQR] age, 60 years [55-65 years]) with a median (IQR) follow-up of 63.3 months (34.1-96.0 months), of whom 2075 (92.3%) received RT. The 72-month cumulative incidence of LRR without RT was 8.0% (95% CI, 3.0%-16.0%) vs 1.1% with RT (95% CI, 0.6%-1.7%) (P < .001). When stratified by RT and ET adherence, patients receiving RT had the lowest LRR risk regardless of ET duration (72-month LRR: RT and ET adherence, 1.1% [95% CI, 0.6%-2.1%] vs RT and ET nonadherence, 0.9% [95% CI, 0.3%-2.1%]). Adherence to ET alone (without RT) had an estimated 72-month LRR of 5.5% (95% CI, 1.0%-16.0%). Those who did not receive RT and were ET nonadherent had an estimated 72-month LRR of 11.0% (95% CI, 3.3%-25.0%). No association was observed between receipt of RT and OS (P = .2). In this cohort study of patients aged 50 to 69 years who underwent lumpectomy for early-stage breast cancer with ODX RS of 18 or below, we found significantly lower estimated LRR rates among those who completed at least 1 form of adjuvant therapy. For patients willing to accept a low absolute risk, but slightly higher relative risk of LRR with de-escalated therapy, ODX RS may be a valuable tool in selecting younger candidates for RT omission than current guidelines support.