282 - Early-Stage Breast Cancer with Low Genomic Risk: Optimizing Adjuvant Therapy

Purpose/Objective(s): There is significant interest in de-escalating adjuvant therapy for early-stage, low-risk breast cancer. While omission of radiotherapy (RT) is feasible for select older patients with favorable clinicopathologic features, ongoing studies aim to expand de-escalation options for younger patients by incorporating molecular and genomic biomarkers, such as the Oncotype DX 21-gene recurrence score (ODX RS). We evaluated outcomes of treatment de-escalation for younger patients aged 50-69 with early-stage breast cancer and an ODX RS =18.

Materials/Methods: Using a prospectively maintained institutional database, we studied patients aged 50-69 with T1N0, hormone receptor-positive and HER2-negative breast cancer, with an ODX RS =18. All patients were treated with breast conserving surgery and endocrine therapy (ET), with or without adjuvant RT. Patients were considered adherent to ET if they received =5 years of ET, or if it was ongoing at the time of last follow-up; non-adherence included halting ET within <5-years of initiation. Cumulative incidence of locoregional recurrence (LRR) was the primary endpoint, with death and non-local-regional events as competing risks.

Results: We ascertained 2249 patients with a median follow-up of 63.4 months, of whom 2075 (92%) received adjuvant RT. The 72-month cumulative incidence of LRR without RT was 8.0% (95% CI: 3.0%-16%) versus 1.1% with RT (95% CI: 0.6%-1.8%) (p<0.001). When further stratified by both RT and ET adherence, patients receiving RT had the lowest LRR risk regardless of ET duration (Table 1). Adherence to endocrine therapy alone (without RT) had the second highest 72-month LRR estimate, and the highest cumulative incidence estimates of LRR were observed among those who did not receive RT and were ET non-adherent. No association was observed between receipt of RT and OS (p = 0.2).

Conclusion: Patients aged 50-69 have excellent outcomes with or without RT following lumpectomy for early-stage breast cancer with ODX RS =18, provided they adhere to ET. Notably, the lowest LRR risk was observed with RT, regardless of ET adherence. Our findings are consistent with those of landmark radiotherapy omission trials and support ongoing evaluations of adjuvant therapy optimization for younger patients using ODX RS, such as on the IDEA and DEBRA (NRG BR007) trials. ODX RS may be a valuable tool in selecting appropriate candidates for RT omission among younger patients aged 50-69 with T1N0, hormone-receptor positive, HER2-negative breast cancer. Ongoing studies will evaluate the feasibility of endocrine therapy omission in the context of RT.