NRG-BR-008: A Phase III Randomized Trial of Radiotherapy Optimization For Low-Risk HER2-Positive Breast Cancer (HERO)

Authors

• M P. Mitchell
• L Z. Braunstein
• H Bandos
• W M. Sikov
• A J. Khan
• Peter Y. Chen, Corewell Health East
• P A. Ganz
• R Jagsi
• J R. White
• R S. Cecchini
• H Kang
• S L. Puhalla
• K L. Bolton
• E P. Connolly
• E Stringer-Reasor
• K R. Gergelis
• T B. Julian
• E P. Mamounas
• N Wolmoark

Document Type

Conference Proceeding

Publication Date

2-15-2026

Publication Title

Clinical Cancer Research

Abstract

Breast radiotherapy (RT) is the standard of care for patients with early-stage breast cancer (BC) who undergo breast-conserving surgery (BCS). However, the magnitude of benefit of RT is less clear in BCS patients with low-risk disease who receive effective systemic therapy. Among patients with early-stage HER2-positive (HER2+) BC, 10-year locoregional recurrence has been reported as low as 1.5% following BCS, adjuvant chemotherapy and HER2-targeted therapy, and RT. Given these exceedingly favorable outcomes, with the addition of HER2-directed therapy, we seek to evaluate the feasibility of omitting RT among patients with early-stage HER2+ BC following BCS and appropriate systemic therapy. This is a phase III randomized trial for patients ≥18 years with early-stage, node-negative, HER2+ (IHC/FISH) BC treated with BCS with negative margins and sentinel lymph node biopsy or axillary dissection. Patients undergoing primary surgery must have pathologic T1 (≤3 cm) N0 disease, whereas patients receiving neoadjuvant therapy must have clinical T1-2 (≤5 cm) N0 disease and exhibit a pathologic complete response (ypT0N0) at surgery. Patients with residual non-invasive disease (DCIS) in the surgical specimen (ypTis) are eligible if residual DCIS spans ≤1 cm and surgical margins are negative for DCIS. All patients must receive systemic therapy and HER2-targeted therapy, either in the adjuvant or neoadjuvant setting. Stratification is by age (< 60; ≥60), tumor size (≤1 cm; >1 cm), estrogen-receptor status (positive; negative), and systemic therapy sequencing (adjuvant v neoadjuvant). Patients will be randomized to standard breast RT in addition to continuation of HER2-targeted therapy to complete one year of treatment (Arm 1), or HER2-targeted therapy alone (Arm 2). Endocrine therapy will be recommended for patients with hormone-receptor positive tumors. The primary endpoint is the recurrence-free interval (RFI). Secondary endpoints include time to ipsilateral breast recurrence, locoregional recurrence, disease-free survival, and overall survival, in addition to the 7-year ipsilateral breast recurrence rate among those not receiving RT. A health-related quality of life sub-study will assess differences in patient-reported breast pain and worry. We estimate a 7-year RFI of 97.5% with RT and allow for a clinically acceptable decrement of 3.63% without RT (7-year RFI of 93.87%; HR 2.5) to establish omission of RT as non-inferior. NRG-BR008 aims to enroll 1,300 patients over 7.25 years, yielding 80% power to detect the non-inferiority of RT omission with a one-sided α=0.05. We expect to observe the required 38 RFI events within 4.5 years of additional follow-up. The NRG-BR008/HERO trial opened to accrual in March 2023. Accrual is 103/1,300 as of July 9, 2025.

Volume

32

Issue

4 Suppl

First Page

PS5-07-02

Last Page

PS5-07-02

Recommended Citation

Mitchell MP, Braunstein LZ, Bandos H, Sikov WM, Khan AJ, Chen PY, et al. NRG-BR008: a phase III randomized trial of radiotherapy optimization for low-risk HER2-positive breast cancer (HERO). Clin Cancer Res. 2026 Feb 15;32(4 Suppl):PS5-07-02. doi:10.1158/1557-3265.SABCS25-PS5-07-02

Comments

San Antonio Breast Cancer Symposium, December 9-12, 2025, San Antonio, TX

DOI

10.1158/1557-3265.SABCS25-PS5-07-02