Abstract 3692: PRECISION (Profiling Early Breast Cancer for radiotherapy Omission): An ongoing phase II study of breast-conserving surgery without adjuvant radiotherapy for favorable-risk breast cancer
Authors: Braunstein Lior Zvi , Iannone Ashley , Taghian Alphonse G. , Wong Julia , Bellon Jennifer , Harris Jay R. 
Published: August 2018

Abstract
Background: Radiation therapy (RT) following breast conserving surgery (BCS) is well-known to improve outcomes for invasive breast cancer. However, RT can be resource-intensive, disruptive, and confers a small risk of long-term adverse effects. In addition, reports have suggested that not all patients stand to benefit equally from RT, with certain 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. However, distinguishing luminal A cancers from their less-favorable luminal B counterparts remains a challenge. This trial employs molecular profiling to identify favorable-risk, early-stage breast cancer patients who may safely omit RT following BCS.
Methods: To identify a low-risk, luminal A cohort, we are employing well-characterized clinicopathologic parameters in addition to molecular profiling. Eligible patients are 50-75 years of age and must have invasive breast cancer ≤2 cm (T1), that is estrogen or progesterone receptor positive, low- or intermediate-grade, without HER2 amplification, and with negative margins (no ink on tumor) following BCS. Following resection, tumor samples 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 of recurrence score) are 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 is LRR at 5 years; a rate of &lt;5% will be considered of interest. Projected accrual is 345 patients 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.
Results: PRECISION opened to accrual in April 2016 and, as of October 2017 has registered 57 patients to undergo molecular risk profiling. Of these, 2 (3.5%) withdrew consent prior to receiving their PAM50 results and 11 (19.3%) were ineligible based on their risk-of-recurrence score, leaving 43 patients eligible for the omission of RT. Of these, 4 (7.0%) ultimately chose to undergo RT, while 39 (68.4%) opted to omit RT on the investigational arm of the study.
Conclusions: The omission of RT is of interest to low-risk breast cancer patients. The safety and feasibility of this approach is currently being studied.
Citation Format: Lior Zvi Braunstein, Ashley Iannone, Alphonse G. Taghian, Julia Wong, Jennifer Bellon, Jay R. Harris. PRECISION (Profiling Early Breast Cancer for radiotherapy Omission): An ongoing phase II study of breast-conserving surgery without adjuvant radiotherapy for favorable-risk breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3692.