Internal mammary and medial-supraclavicular irradiation reduces breast cancer mortality without improving overall survivalTrial shows specific radiation reduces breast cancer deaths over 20 years

The Lancet. Oncology Published July 22, 2026 Study authors: Kaidar-Person Orit, Weltens Caroline G, Fortpied Catherine, Scheijmans Luc J E E, Kirkove Carine Y, … PubMed ↗ NCT00002851 ↗ DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Note that IM-MS irradiation reduces breast cancer mortality but does not improve overall survival in this population.

The study investigated the impact of internal mammary and medial-supraclavicular (IM-MS) irradiation compared to standard treatment for women with early stage breast adenocarcinoma. The trial followed a large cohort over a long period to assess primary outcomes including overall survival and secondary outcomes such as mortality from specific causes and late radiation effects.

Results indicated that patients receiving IM-MS irradiation experienced lower rates of breast cancer mortality at the 20-year mark compared to the control group. However, this reduction did not result in a statistically significant difference in overall survival. The authors noted that the IM-MS group experienced higher cumulative mortality from causes unrelated to breast cancer, which balanced the observed benefit in cancer-specific mortality.

Safety data showed instances of late cardiac and lung fibrosis in both groups. The authors noted limitations regarding unplanned subset analyses during the study. Clinically, while IM-MS irradiation appears effective at reducing deaths specifically from breast cancer, it does not currently demonstrate a clear advantage for overall survival. Practitioners should weigh these specific mortality benefits against potential non-cancer related risks when considering treatment plans.

When a person is diagnosed with breast cancer, the goal of treatment is clear: stop the cancer from spreading and keep the patient alive as long as possible. For many patients, doctors must decide on the best way to deliver radiation to ensure the cancer does not return. A large study followed over 4,000 women for more than 20 years to see if a specific type of radiation treatment helped them live longer.

The researchers looked at women with various stages of breast cancer. They split the group into two: one group received a special radiation technique called IM-MS (which targets internal mammary and supraclavicular areas), and the other group did not receive this extra step. The study was massive, involving 46 different centers across 13 countries to ensure the results were as reliable as possible.

The findings were complex. When looking at deaths caused specifically by breast cancer, those who received the IM-MS radiation had a lower mortality rate after 20 years compared to those who did not. However, when looking at overall survival—meaning whether the patients were alive from any cause—there was no difference between the two groups. This happened because the group receiving the extra radiation also saw a higher rate of deaths from other causes that were not related to cancer.

Safety is always a major concern in radiation therapy. The study did note some differences in side effects. For example, more women in the IM-MS group experienced lung fibrosis (scarring of the lung tissue) compared to the control group. There was also a slightly higher rate of cardiac fibrosis (scarring of heart tissue) in the treatment group.

It is important not to jump to conclusions based on this single study. While it shows that the extra radiation might help stop cancer from spreading, it did not result in a longer overall life for the patients. This is because the benefits of stopping the cancer were balanced out by other health issues. For now, this means doctors will continue to weigh the specific risks of lung and heart scarring against the goal of preventing cancer recurrence when deciding on radiation plans.

What this means for you:

Specific radiation reduced deaths from breast cancer but did not improve overall survival over 20 years.

Study Details

Study typeRct

Sample sizen = 4,004

EvidenceLevel 2

Follow-up180.0 mo

PublishedJul 2026

PMID42372743

TrialNCT00002851

View Original Abstract ↓

BACKGROUND: Results from several studies, including our 15-year analysis, showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. Here, we present the scheduled 20-year analysis of the EORTC trial 22922/10925, evaluating the role of internal mammary and medial-supraclavicular (IM-MS) nodal irradiation in patients with stage I-III breast cancer. Patients without confirmed axillary nodal involvement (pathological N stage 0 [pN0]) were eligible for the trial when the primary tumours were centrally or medially located. METHODS: EORTC 22922/10925 was a randomised, open-label, phase 3 trial done across 46 radiation oncology departments from 13 countries. Eligible participants were women up to 75 years of age with unilateral, histologically confirmed, stage I-III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. Only patients without clinically and histopathologically confirmed nodal involvement (pN0) were included in this unplanned subgroup analysis. The primary outcome was overall survival analysed according to the intention-to-treat principle. Safety analyses were conducted in the subset of eligible patients treated per protocol. This trial is registered with ClinicalTrials.gov (on Nov 1, 1999; NCT00002851) and closed after its final analysis. FINDINGS: Between Aug 5, 1996, and Jan 13, 2004, 4004 patients were randomly assigned. 890 (44·5%) of 2002 patients in the IM-MS irradiation group and 888 (44·4%) of 2002 patients in the control group had pN0 disease. The median age of participants was 55 years (IQR 48-63). At a median follow-up of 22·2 years (IQR 20·1-24·5), 276 (31·1%) of 888 patients in the IM-MS irradiation group and 277 (31·1%) of 890 patients in the control group died because of any cause; 87 (31·5%) of 276 and 122 (44·0%) of 277 patients died due to breast cancer, respectively. At 20 years, the overall survival rate was 69·0% (95% CI 65·4-72·3) in the IM-MS irradiation group and 68·4% (64·8-71·6%) in the control group (hazard ratio [HR] 0·98 [95% CI 0·83-1·15], p=0·77). The breast cancer mortality rate was 10·0% (8·0-12·3) in the IM-MS irradiation group and 14·2% (11·9-16·8) in the control group (HR 0·70 [95% CI 0·53-0·92], p=0·010), but cumulative mortality of unknown cause or not breast cancer cause was 20·9% (95% CI 17·9-24·1) in the IM-MS irradiation group and 17·4% (14·7-20·3) in the control group (HR 1·24 [95% CI 1·00-1·53]; p=0·048). In patients with left-sided breast cancer, late cardiac fibrosis occurred in 15 (3·4%) of 445 patients in the IM-MS irradiation group and 12 (2·8%) of 436 patients in the control group. Lung fibrosis at any grade occurred in 55 (6·4%) of 855 patients in the IM-MS irradiation group and 18 (2·1%) of 877 patients in the control group. INTERPRETATION: Breast cancer mortality at 20 years was significantly lower in the IM-MS irradiation group, whereas non-breast cancer mortality was numerically higher in the IM-MS irradiation group after 15 years, resulting in no long-term benefit of IM-MS irradiation on overall survival. Our results emphasise the importance of very long-term follow-up and advanced irradiation techniques to reduce the dose to organs of interest. FUNDING: Ligue Nationale contre le Cancer, KWF Kankerbestrijding, and EORTC Cancer Research Fund.

Internal mammary and medial-supraclavicular irradiation reduces breast cancer mortality without improving overall survivalTrial shows specific radiation reduces breast cancer deaths over 20 years

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