Abstract OT1-12-02: Preliminary report of the PRECISION Trial (Profiling Early Breast Cancer for Radiotherapy Omission): A Phase II Study of Breast-Conserving Surgery Without Adjuvant Radiotherapy for Favorable-Risk Breast Cancer
Authors: Braunstein Lior Z. , Wong Julia , Dillon Deborah A. , Chen Yu-Hui , Catalano Paul , Cahlon Oren , El-Tamer Mahmoud B. , Jimenez Rachel , Khan Atif , Perez Carmen , Punglia Rinaa , Shiloh Ron , Warren Laura , Wazer David , Wright Jean , Buckley Elizabeth , King Tari , Powell Simon , Winer Eric , Bellon Jennifer 
Published: March 2023

Abstract
Background: Breast conserving surgery (BCS) is typically followed by adjuvant radiotherapy (RT) based on several landmark trials demonstrating improvements in disease control and survival. Since completion of these historical trials, the advent of molecular subtyping has revealed that breast cancer is not a single disease entity, but rather a class of cancers with differential risk profiles. We evaluated whether RT could be safely omitted following BCS for patients with the most favorable subtype as defined by the Prosigna PAM50 assay. Methods: We conducted a multicenter prospective single-arm cohort study with IRB approval and an FDA investigational device exemption (IDE). Eligible patients were women 50 to 75 years of age (inclusive) who had undergone BCS revealing tumors ≤2cm in size, that were estrogen or progesterone receptor positive (HR+), HER2 negative, grade 1-2, node negative (N0), with negative excision margins (no ink on tumor). Intent to take endocrine therapy was required. Upon registration, tumors were submitted for central Prosigna testing and those with Risk of Recurrence (ROR) score ≤40 were deemed eligible for the investigational omission of RT. The primary endpoint was the 5-year locoregional recurrence rate (LRR). Anticipating a total of 345 RT-omitting patients to enroll over 3.5 years, the study was designed with 90% power to exclude a 5-year LRR of 5% using a one-sample exponential test with one-sided type I error of 0.025. Results: From 2016 to 2020, 671 patients were registered from 13 centers, inclusive of affiliated regional network sites. Of these, 382 patients had a ROR Score ≤40 and opted to forego RT, comprising the main intention-to-treat (ITT) study population. Median age was 65 years (range 50 to 75), and median tumor size was 0.9 cm (range 0.1 to 2.0 cm). At a median follow-up of 26.9 months, 12 events were observed: 4 patients had ipsilateral in-breast recurrences, 7 had contralateral breast cancers, and 1 developed an unrelated melanoma. There were no regional-nodal or distant recurrences. The 2-year cumulative rate of LRR was 0.3% (95% CI: 0 – 1.0%). Of the 4 ipsilateral breast recurrences, 2 were in the same quadrant as the original primary tumor. Conclusion: In this preliminary report of the PRECISION trial, patients 50-75 years of age undergoing BCS and endocrine therapy for pT1N0 HR+ HER2-negative breast cancer with ROR score ≤40 had exceedingly low rates of LRR in the absence of adjuvant RT at a median follow-up of 26.9 months. Additional follow-up is required to determine whether these favorable results are durable.
Citation Format: Lior Z. Braunstein, Julia Wong, Deborah A. Dillon, Yu-Hui Chen, Paul Catalano, Oren Cahlon, Mahmoud B. El-Tamer, Rachel Jimenez, Atif Khan, Carmen Perez, Rinaa Punglia, Ron Shiloh, Laura Warren, David Wazer, Jean Wright, Elizabeth Buckley, Tari King, Simon Powell, Eric Winer, Jennifer Bellon. Preliminary report of the PRECISION Trial (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 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-02.