Landmark trial evaluates chemotherapy benefit in high-risk early-stage breast cancer

by ECOG-ACRIN Cancer Research Group

edited by Sadie Harley, reviewed by Andrew Zinin

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The addition of CDK4/6 inhibitors to endocrine therapy has changed the standard of care for patients with high-risk, early-stage estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer by reducing the risk of recurrence. However, one patient subgroup continues to present a clinical dilemma. In current practice, patients with low genomic risk but high anatomic risk receive adjuvant chemotherapy because of large tumors or significant lymph node involvement, even though their tumors may have lower-risk biology.

The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) has launched the RxFINE-Low (EA1242) trial to determine whether chemotherapy provides additional benefit for this subgroup.

"RxFINE-Low seeks to answer a critical question in breast cancer care, which is: Can patients with high anatomic risk but low genomic risk do similarly well without chemotherapy?" said study chair Nancy Chan, MD, a medical oncologist at New York University's Perlmutter Cancer Center at NYU Langone.

Adjuvant chemotherapy is generally not recommended for postmenopausal patients with earlier-stage ER+/HER2- breast cancer who have low Oncotype DX scores and cancer in up to three lymph nodes, based on findings from the landmark TAILORx and RxPONDER trials.

However, whether chemotherapy can also be omitted in patients with larger tumors or more extensive lymph node involvement has never been evaluated in a large prospective randomized trial. As a result, chemotherapy remains the standard approach for these patients.

The NATALEE and monarchE trials established the benefit of adding a CDK4/6 inhibitor to endocrine therapy in high-risk, early-stage ER+/HER2- breast cancer. However, most participants had already received chemotherapy before enrolling in those studies. As a result, the trials could not evaluate the additional benefit of chemotherapy.

RxFINE-Low is the first prospective randomized Phase III trial specifically designed to answer this question in patients with high anatomic risk but low genomic risk. The study will enroll nearly 2,000 postmenopausal women and men with high anatomic risk breast cancer, defined as a tumor larger than 5 cm (2 inches) or cancer in more than three lymph nodes, and low genomic risk, indicated by an Oncotype DX Breast Recurrence Score between 0 and 25.

Participants will be randomly assigned in a 1:1 ratio to receive either the current approach of adjuvant chemotherapy followed by endocrine therapy plus a CDK4/6 inhibitor (ribociclib) or endocrine therapy plus ribociclib alone. The primary endpoint is invasive breast cancer-free survival.

"RxFINE-Low will assess whether tumor biology, rather than anatomic tumor burden alone, can guide treatment decisions, and whether chemotherapy can be omitted in some patients," Chan noted.

Participants will be followed for up to 10 years to evaluate recurrence, survival, treatment-related side effects and other study endpoints. Researchers will also collect tumor tissue and blood samples to support future translational research.

"As treatment options evolve, we need equally rigorous evidence to determine which patients may omit chemotherapy," Chan said. "RxFINE-Low is designed to provide us with prospective evidence in this space."

If chemotherapy can be omitted, the findings could spare many patients short- and long-term toxicities. The trial results could also provide prospective evidence to help inform future coverage decisions. Because genomic testing has not been prospectively validated in patients with high anatomic risk breast cancer, many insurers do not routinely cover Oncotype DX testing for these patients.

Key medical concepts

Chemotherapy, AdjuvantOncotype DX Breast Recurrence Scoreribociclib

Clinical categories

Oncology Provided by ECOG-ACRIN Cancer Research Group Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

Citation: Landmark trial evaluates chemotherapy benefit in high-risk early-stage breast cancer (2026, September 24) retrieved 25 September 2026 from https://medicalxpress.com/news/2026-09-landmark-trial-chemotherapy-benefit-high.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.