Long-term trial challenges assumptions about lymph node radiation therapy in breast cancer

by European Organisation for Research and Treatment of Cancer

edited by Lisa Lock, reviewed by Robert Egan

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Final results from a landmark EORTC randomized trial with more than 20 years of follow-up show that irradiation of the internal mammary and medial supraclavicular lymph nodes reduces breast cancer mortality but does not improve overall survival. The findings highlight the importance of very long-term follow-up when evaluating cancer treatments, particularly in patients with an otherwise favorable prognosis.

The results stem from EORTC trial 22922/10925 and were presented at the ESTRO 2026 Congress in Stockholm during the plenary session: Joint Green Journal—The Lancet Oncology Top Clinical Trials. Reflecting the strength and clinical relevance of these findings, the planned 20-year analysis of the full trial population has been simultaneously published in CA: A Cancer Journal for Clinicians, while The Lancet Oncology has accepted to publish soon a complementary paper reporting an unplanned subset analysis in the patients with node-negative (pN0) breast cancer.

Between 1996 and 2004, the trial enrolled 4,004 patients with stage I–III breast cancer at 46 centers in 13 countries. Patients were randomized to receive postoperative radiation therapy with or without elective irradiation of the internal mammary and medial supraclavicular (IM-MS) lymph nodes. At final analysis, the median follow-up was 22.2 years — the longest planned, as well as median, follow-up of any randomized breast cancer radiation therapy trial.

Long-term outcomes across the overall trial population

At 20 years, overall survival was similar in patients treated with or without IM-MS irradiation. However, breast cancer–related mortality was significantly lower among patients who received IM-MS irradiation. This benefit was counterbalanced over time by an increase in deaths from causes other than breast cancer, which emerged after approximately 15 years, resulting in no survival advantage.

Long-term cardiac and pulmonary toxicity was reported more frequently after IM-MS irradiation, although severe side effects remained very uncommon. Of note, patients were treated using radiation therapy techniques available more than two decades ago.

Outcomes in node-negative breast cancer patients

The proffered paper presented at ESTRO also included the subset analyses on the 1,778 patients with node-negative (pN0) breast cancer and centrally or medially located tumors. Despite a lower absolute risk of breast cancer death in this group, the long-term pattern closely mirrored that of the overall trial population.

Reductions in breast cancer mortality were again offset by a later increase in non–breast cancer–related deaths, resulting in no improvement in overall survival. These findings suggest that long-term trade-offs must be considered even in patients with a favorable prognosis and call for careful evaluation of nodal irradiation in axillary-node-negative disease.

"This trial clearly shows why long-term follow-up over decades is essential in breast cancer," said Prof. Philip Poortmans, study coordinator. "Short or medium term benefits may not reflect the full balance between efficacy and late side effects, particularly in patients with an otherwise favorable prognosis," added Prof Orit Kaidar-Person, Associate Member of the EORTC Breast Cancer Group.

"Such large, decades-long trials with rigorous quality assurance, allowing clinically meaningful subgroup analyses, are only possible thanks to the sustained support and collaboration fostered by organizations like EORTC," agreed both study coordinators.

Why this trial matters

• It provides the longest planned, as well as median follow-up, of any randomized breast cancer radiation therapy trial.
• It shows that treatment benefits and risks continue to evolve well beyond 15–20 years.
• It demonstrates that node-negative patients experience similar long-term trade-offs as the overall trial population.
• It informs ongoing discussions on optimizing and potentially de-escalating treatments in favorable-risk breast cancer.

Conducted by the EORTC Radiation Oncology and Breast Cancer Groups, trial 22922/10925 remains a cornerstone study for understanding the long-term impact of locoregional treatments in breast cancer and for guiding future research aimed at improving both survival and quality of life.

Publication details

Orit Kaidar‐Person et al, Twenty-year results of the randomized European Organization for Research and Treatment of Cancer trial 22922/10925 evaluating internal mammary chain and medial supraclavicular lymph node irradiation in stage I–III breast cancer, CA: A Cancer Journal for Clinicians (2026). DOI: 10.3322/caac.70082

ESTRO 2026 presentation number: 5580 Internal Mammary and Medial Supraclavicular irradiation in stage I-III breast cancer: 20 years results of the randomized EORTC trial 22922/10925, including in pN0 patients (Presenter: Philip Poortmans & Orit Kaidar-Person)

Journal information: Lancet Oncology

Key medical concepts

Breast CarcinomasOverall Survival

Clinical categories

Oncology Provided by European Organisation for Research and Treatment of Cancer Who's behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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