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

Stockholm, Sweden, 17 May 2026 — Final results from a landmark EORTC randomised 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 otherwise favourable 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 centres in 13 countries. Patients were randomised 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 randomised breast cancer radiation therapy trial.

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.

Find out more here.

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 tumours. 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 favourable prognosis and call for careful evaluation of nodal irradiation in axillary‑node‑negative disease.

“Short or medium term benefits may not reflect the full balance between efficacy and late side effects, particularly in patients with an otherwise favourable 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 organisations like EORTC,” agreed both study coordinators.

The investigators note that advances in modern radiation therapy planning and delivery, sharply reducing radiation exposure to organs such as the heart and lungs, very likely improves the balance between benefits and risks for patients treated today.

• It provides the longest planned, as well as median follow-up, of any randomised 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 optimising and potentially de-escalating treatments in favourable-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.

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

Funding: This study was supported by donations from the La Ligue nationale contre le cancer from France; the KWF Kanker Bestrijding from the Netherlands; and from the Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society from Belgium.

The fellowship of Lydia Champezou was financially supported by the EORTC Cancer Research Fund (ECRF).

The European Organisation for Research and Treatment of Cancer (EORTC) is a non-governmental, non-profit organisation, which unites clinical cancer research experts, throughout Europe, to define better treatments for cancer patients to prolong survival and improve quality of life. Spanning from translational to large, prospective, multi-centre, phase III clinical trials that evaluate new therapies and treatment strategies as well as patient quality of life, its activities are coordinated from EORTC Headquarters, a unique international clinical research infrastructure, based in Brussels, Belgium.

EORTC Communications
Caroline Moulins, Head of Communications
T: +32 2 774 13 68
E: caroline.moulins@eortc.org