Definitive, stereotactic ablative radiotherapy and endocrine therapy without surgery for select low-risk breast cancers: A prospective, phase II trial.

Abstract

Early-stage, hormone receptor positive (HR+) breast cancer has excellent outcomes with lumpectomy, radiotherapy, and endocrine therapy (ET), prompting interest in treatment de-escalation. Advances in stereotactic ablative radiotherapy (SABR) raise the possibility of definitive local therapy without surgery in select patients. We conducted a prospective, phase II trial (NCT02945579) evaluating SABR with ET as a non-operative strategy. Patients aged ≥ 40 years with cT1N0M0, unicentric, HR+, HER2-negative breast cancer received 3 months of ET followed by SABR in 5 fractions. Vacuum-assisted image-guided core biopsy of the tumor bed was performed 6-12 months after SABR. Patients with pathologic complete response (pCR) omitted surgery. Co-primary endpoints were pCR and 3-year progression-free survival (PFS) rates. Patient-reported outcomes were collected as a secondary endpoint. A Bayesian framework evaluated futility using posterior probabilities to assess a clinically meaningful pCR rate. Twenty patients were enrolled (median age 70.5 years). Nineteen underwent biopsy after SABR. pCR was observed in 10/19 patients (53%, 95% CI 30-73%), and 7 (37%) had near complete response. Among the 12 patients managed without surgery, median follow-up was 44.9 months. Three-year PFS was 92% (95% CI 54-99%), with one non-breast cancer-related death and no breast cancer recurrences. Longitudinal patient-reported outcomes of decisional regret and breast-specific outcomes remained stable. Definitive SABR combined with ET achieved substantial pCR rates and encouraging tumor control. These findings support further evaluation of radiotherapy-based definitive treatment and potential surgery omission in carefully selected patients with favorable, HR + breast cancer.