Abstract CT077: PRECISION (Profiling Early Breast Cancer for Radiotherapy Omission): a phase II study of breast-conserving surgery without adjuvant radiotherapy for favorable-risk breast cancer

Abstract

Abstract Background: Radiation therapy (RT) following breast conserving surgery (BCS) is well-known to improve outcomes for patients with invasive breast cancer. However, RT poses an inconvenience to patients and confers a small, yet real, risk of long-term adverse effects. In addition, reports have suggested that not all patients stand to benefit equally from RT, with certain disease features portending an excellent prognosis regardless of the adjuvant treatment approach. Specifically, favorable luminal A cancers exhibit a 10-year locoregional recurrence (LRR) rate of 2% following BCS and RT, suggesting very low putative risk in the absence of RT. While luminal A breast cancers are the most favorable among subtypes, robustly distinguishing them from luminal B tumors is a challenge. This trial seeks to employ a molecular profiling approach to identify favorable-risk, early-stage breast cancer patients who may feasibly omit RT following BCS. Methods: To identify a low-risk, luminal A cohort of breast cancer patients, we will employ well-characterized clinicopathologic parameters in addition to molecular profiling. Eligible patients will be 50-75 years of age and must have invasive breast cancer ?2 cm (T1), that is estrogen receptor positive, low- or intermediate-grade, without HER2 amplification, and with negative margins (no ink on tumor) following BCS. Following resection, tumor samples will undergo prediction analysis of microarray 50 (PAM50) profiling via the NanoString Prosigna assay to characterize intrinsic biologic subtype. Patients with tumors classified as luminal A (low-risk score) will be eligible for the omission of RT. The trial is a single-arm prospective cohort study designed to assess the viability of RT omission in this favorable population. The primary endpoint will be LRR at 5 years and a rate of <5% will be considered of interest. Projected accrual will be 345 patients to be enrolled over 4 years. Using this design, the study has 90% power to distinguish a 5-year LRR rate of 1% from 5% using a one-sample exponential test with one-sided type I error of 0.025. Secondary endpoints include 5- and 10-year recurrence rates of any type (local, regional and/or distant), disease-free survival, invasive-disease-free survival and overall survival, in addition to rates of salvage mastectomy and radiotherapy. (ClinicalTrials.gov: NCT02653755) Citation Format: Lior Z. Braunstein, Alphonse G. Taghian, Jay R. Harris. PRECISION (Profiling Early Breast Cancer for Radiotherapy Omission): a phase II study of breast-conserving surgery without adjuvant radiotherapy for favorable-risk breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT077.