Congress Report

By the ESTRO breast focus group

The field of breast cancer radiotherapy continues to evolve rapidly, driven by advances in clinical understanding and technological innovation. The ESTRO 2025 congress provided an essential platform from which the latest developments and clinical evidence in breast cancer radiotherapy were presented. Sessions were focused on evolving treatment paradigms, patient selection strategies, safety considerations, and technical innovations. Below are key takeaways that are relevant to breast cancer radiotherapy clinical practice, drawn from various presentations at the meeting.

What is the breast journey?

The breast cancer ‘journey’ was a specific programme created by members of the ESTRO breast focus group to enable those interested in breast cancer to follow the key sessions so as not to miss any of the highlights of the congress. The programme was available on the ESTRO website. The congress sessions were also reported by social media ambassadors. For the first time, a special period was set aside during the meet-and-greet session that enabled everyone to present projects and network with colleagues from all over Europe. We will see you next year for an improved journey based on feedback from this first edition.

Late-breaking papers

This session included long-term results of the FAST-Forward study by Prof Murray Brunt and of the Danish Breast Cancer Co-operative Group (DBCG) Skagen Trial 1 by Prof Birgitte Offersen (1,2).

In the FAST-Forward trial, researchers evaluated whether a shortened, one-week adjuvant radiotherapy schedule (five fractions (Fr)) was as safe and effective as the standard three-week regimen (40Gy in 15Fr) for patients with early breast cancer. Over 4,100 patients were randomised to receive either 27Gy/5Fr, 26Gy/5Fr, or the standard 40Gy/15Fr. After five years, both one-week regimens were shown to be non-inferior in terms of local recurrence (LR), with the 26Gy/5Fr schedule having similar normal tissue effects to the standard treatment, making it the preferred option (1).

The trial’s 10-year follow-up data, now complete and presented at ESTRO 2025 in Vienna, includes long-term outcomes on recurrence, survival, side effects, and patient-reported quality of life. With 116 ipsilateral breast recurrences recorded at a median follow-up of 10 years, the analysis confirmed the durability of safety and efficacy for the one-week radiotherapy schedule and reinforced its role as a new standard of care (1).

The DBCG Skagen Trial 1 was set up to assess whether moderately hypofractionated loco-regional radiotherapy (40Gy in 15Fr) was as safe as the standard regimen (50Gy/25Fr) in patients with node-positive breast cancer, with a primary focus on arm lymphoedema at three years (2). A total of 2,963 patients were randomised equally between the two groups, with the majority undergoing either sentinel node biopsy (33%) or axillary lymph node dissection (67%). At a median follow-up of 4.1 years, the three-year lymphoedema rates were similar: 9.0% in the 50Gy group vs. 8.3% in the 40Gy group, a non-significant difference. Cumulative incidence estimates and subgroup analyses (by surgical type and fractionation) showed no statistically significant differences in rates of lymphoedema or shoulder motion. Importantly, hypofractionated radiotherapy did not increase the risk of loco-regional or distant recurrence, but the five-year risk of death from breast cancer was slightly higher in the 40Gy group (7.2% vs. 5.1%, p=0.02).

As discussant Prof Meattini stated, hypofractionated loco-regional radiotherapy appears safe in terms of lymphoedema and recurrence risk, but the observed higher rates of breast-cancer-specific mortality after five years in the 40Gy group raise questions for further investigation.

Oral Presentations

Updates on Ultra-hypofractionated axillary radiotherapy

The FAST-Forward triallists, who had shown that a one-week radiotherapy schedule (26Gy/5Fr) to the breast or chest wall was as safe and effective as the standard three-week schedule (40 Gy/15Fr) for early breast cancer, presented new findings from the prospective, randomised FAST-Forward nodal sub-study (3). In this sub-study, the safety of the delivery of five-fraction (one-week) schedules for adjuvant radiotherapy to the axilla (any or all levels I-IV) in patients with invasive breast cancer (pT1-3 pN1-3a M0) who required axillary radiotherapy was evaluated.

The primary five-year analysis was focused on normal tissue effects, particularly patient-reported arm/hand swelling, which was the primary endpoint. Results in 467 patients showed similar rates: 10% in the 40Gy group vs. 11% in the 26Gy group (p=0.49), meeting non-inferiority criteria. Clinician-reported lymphoedema rates were also comparable (10% vs. 14%; p=0.27), with no reported cases of brachial plexopathy. Arm and shoulder symptoms were similarly distributed across both groups. These findings show that delivery of 26Gy in five fractions to the axilla is safe.

Local recurrence risk and tumour-bed boost

Improved understanding and minimisation of LR remains a central goal in breast cancer treatment. One presentation featured a post-hoc analysis of the DBCG internal mammary node (IMN2) study (4), which had assessed LR after breast-conserving surgery with or without a tumour-bed boost. While the overall 10-year LR rate was low (3.6%), patients aged 50 or older with ER-/HER2- tumours who did not receive a tumour-bed boost had significantly higher LR rates than did those with ER+/HER2- disease (8.3% vs. 2.8% at 10 years). As a result, as of March 2025, the DBCG guidelines now recommend a 16Gy/8Fr boost for all ER-/HER2- patients, regardless of age. However, this benefit must be weighed against the increased risk of late toxicity.

ESTRO 2025 highlighted the emerging role of emulated trials that leveraged large-scale cohort data to answer unresolved questions regarding boost indications, long-term toxicity, and subgroup benefits (5,6). These innovative, data-driven approaches may soon offer robust evidence in areas in which randomised trials are impractical.

Breast cancer salvage strategies: Management of second tumours

In a propensity score-matched cohort from the GEC-ESTRO breast cancer working group database, salvage mastectomy and second-breast-conserving treatment demonstrated comparable efficacy, with no significant differences regarding overall survival rates (approximately 80% at five years), third ipsilateral breast cancer or disease-free survival, for HER2+ and triple-negative tumours (7).

These findings are consistent with a 10-year follow-up study, which showed no statistically significant difference between second-breast-conserving surgery with perioperative high-dose-rate brachytherapy and salvage mastectomy in terms of second recurrence (survival without second ipsilateral breast tumour recurrence: 82% vs. 80%, p=0.298), regional and distant metastasis, or disease-free survival. Notably, overall survival was even higher in the second-breast-conserving therapy group (70% vs. 47%, p=0.027), and 72% of patients in that group had excellent or good cosmetic results (8).

Breast cancer in younger patients

Several presentations highlighted the particular challenges of treating breast cancer in young patients. Post-treatment pregnancy was shown to be safe, including among BRCA-gene carriers and patients with ER+ disease, with a 10-year cumulative pregnancy rate of 22% and no negative impact on oncological outcomes. Early oncofertility counselling is essential for all women of reproductive age, regardless of disease stage or BRCA status, as fertility preservation strategies are effective (9). Breast-conserving surgery in BRCA1 carriers is associated with a higher risk of LR (hazard ratio (HR) = 4.54), although overall survival rates are similar. After unilateral surgery, the 20-year risk of contralateral breast cancer is 27.5%, and the development of a contralateral cancer doubles the risk of breast cancer mortality (HR=2.14). Risk-reduction mastectomy reduces the risk of death by 35% and improves disease-free survival rates by 42% (10). Finally, Prof Meattini confirmed that radiotherapy was safe in BRCA carriers, with no excess acute or late toxicity. However, patients showed an increased risk of contralateral breast cancer after radiotherapy (HR=1.44), a finding that supported the use of dose-sparing techniques and individualised planning (11).

Safety Considerations

Modern breast radiotherapy is safer than ever, but the minimisation of dose to organs at risk remains a priority (12). The DBCG presented new, pragmatic dose constraints for the heart, lungs, and contralateral breast, which had been derived from national trial data and were now implemented across Denmark (13). For example, for left-sided breast irradiation, the DBCG recommends a mean heart dose of below 1.5Gy (80th percentile) and 2.5Gy (95th percentile), and in cases in which lymph nodes are included, 3.5Gy (80th) and 5Gy (95th). This “stoplight” system (green/yellow/red) helps clinicians to identify quickly those plans that are at risk of exceeding safe thresholds, and this system therefore supports both quality assurance and patient safety.

A post-hoc analysis of the DBCG hypofractionation and partial breast irradiation (PBI) trials investigated the impact of repeat surgery and tumour-bed boost due to incomplete margins on breast induration (14). The results showed that the five-year cumulative incidence of grade 2-3 breast induration was 14.9% for patients without repeated surgery (RS) and 19.7% with RS (adjusted HR 1.32, p=0.046). The combination of RS and boost resulted in the highest risk of breast induration: 30.7% (adjusted HR 3.42, p<0.001). The risk was also higher with boost alone compared with RS alone (25.7% vs. 18.1%). These findings highlight the need for multidisciplinary discussion for patients with narrow surgical margins to balance local control and toxicity.

Evolution of accelerated partial breast irradiation selection criteria

There was significant focus on the refinement of patient selection for accelerated PBI (APBI). The GEC-ESTRO breast cancer working group drew on clinical evidence that had been collected through a systematic search spanning 2010 to 2024 to present updated recommendations (15). The group analysed 10 prospective randomised clinical trials with a minimum median follow-up of five years in the review. Good candidates for APBI are considered to be patients aged at least 40 years with unicentric, unifocal, pTis, T1-2 (≤30mm) pN0, or pN1mi breast cancer of all histology types. Importantly, these candidates should not have an extensive intraductal component or extensive lympho-vascular invasion, and must have negative surgical margins according to National Surgical Adjuvant Breast and Bowel Project criteria. Conversely, the high-risk group, for whom APBI is considered contraindicated, includes patients with BRCA 1-2 mutations or those aged ≤40 years. Other contraindications for APBI in this group include positive margins, multicentric tumours, large tumours (>30mm), triple-negative tumours, the presence of extensive intraductal components, macrometastatic positive lymph nodes (≥pN1a), or unknown axillary status (pNx).

Artificial intelligence in breast radiotherapy: A new era begins

Artificial intelligence (AI) is revolutionising breast radiotherapy, notably through auto-contouring and automated treatment planning. Deep-learning models now deliver highly accurate breast and organ-at-risk contouring, and performance for lymph nodes and tumour beds is improving (16). These tools save time and enhance standardisation, with national projects such as the DBCG’s model leading the way. Automated planning is becoming essential, as breast radiotherapy represents 25-30% of treatment volumes, and cancer cases are expected to rise by 40% by 2040. Centres such as the University of Florence (Italy) are transitioning from manual to automated volumetric modulated arc therapy planning (17). AI also supports quality assurance as it can be used to audit dose delivery trends and to predict quality assurance failures. Additionally, predictive models, such as those developed through the ARTILLERY project, are intended to identify patients at risk of late effects through the use of routine CT data (18). AI is thus set to play a key role across the breast radiotherapy workflow.

Simon Delaunay, MD

Department of Radiotherapy

Gustave Roussy, Villejuif, France

 

Yasemin Bolukbasi

Department of Radiation Oncology

Koc University

Istanbul, Turkey

 

Alizée Camps-Malea, MD
Department of Radiation Oncology

Gustave Roussy

Villejuif, France