SGBCC 2025: strategies of risk-adapted modern radiotherapy in early breast cancer

Modern radiotherapy in early breast cancer uses advanced technologies in imaging, treatment planning and treatment delivery for more accurate target coverage, while minimizing harm to healthy tissue. De-escalation in breast irradiation is mainly achieved by treatment time reduction using hypofractionation and treatment volume reduction using partial breast irradiation. The St. Gallen International Breast Cancer Conference (SGBCC) 2025 highlighted several strategies of risk-adapted modern radiotherapy in early breast cancer, which are discussed here referring to the most important landmark trials.

Hypofractionation is one of the most successful developments in breast radiotherapy over the last two decades. Historically, conventional fractionated breast radiotherapy consisted of 50 Gy in 25 fractions (treatments) over 5 weeks, with an additional local boost up to 6–7 weeks. Radiobiologic characteristics of breast cancer cells led to the development of hypofractionated radiotherapy by increasing the dose per fraction > 2 Gy, while reducing the total dose and treatment time, based on the assumption of equivalent biological effectiveness compared to conventional treatment. Numerous prospective clinical trials have evaluated effectiveness of moderate hypofractionation (15–16 fractions in 3 weeks) in the setting of whole breast irradiation (WBI) and postmastectomy radiotherapy (PMRT). Especially data from the START Trialists’ Group [1] and Ontario trial [2] showed no evidence of a differential effect of fractionation schedule for tumour control by age, type of primary surgery, axillary node status, tumour grade, use of adjuvant chemotherapy or boost radiotherapy. While, based on all these data, moderate hypofractionation in WBI has already been established as standard therapy, there are still concerns about acute and long-term toxicity (lymph oedema, shoulder stiffness, plexus liaison) in moderate hypofractionated nodal radiotherapy. Based on data from the UNICANCER HypoG-01 phase III trial [3] and the SKAGEN‑1 trial [4], no statistical differences can be demonstrated in late normal tissue effects, including lymphoedema. Concerning moderate hypofractionation after breast reconstruction, results from the randomized controlled FABREC trial were published by Wong et al. [5] comparing quality of life (QoL) and local outcomes after immediate implant-based reconstruction between the different fractionation schemes. After a median follow-up of 31.8 months there were no significant differences in physical wellbeing and overall toxicity between the two regimes. Preliminary results from the randomized controlled RT CHARM trial [6], recently presented at ASTRO 2024, also demonstrated no differences regarding the rate of reconstruction-associated complications after 2 years. Based on these data, there is clear evidence that in 2025 moderate hypofractionation is the standard treatment in WBI, partial breast irradiation (PBI), and PMRT with or without reconstruction and lymph node irradiation. With the indication for local boost therapy, data from the START trials and Canadian trial provide sufficient data for a safe sequential application, prolonging treatment for at least another 4 days. With a simultaneously integrated boost, by escalating the dose in the former tumour bed while delivering a standard dose to the remaining breast tissue, treatment burden can be reduced to 15 fractions. The IMPORT-HIGH trial [7] and NRG RTOG 1005 trial [8] resulted in very low 5‑year in breast tumour recurrence rates (2 and 2.2%) with no differences in toxicity or cosmetic outcome for simultaneous versus sequential boost.

Beside moderate hypofractionation in 3 weeks there is a clear trend toward further reduction of fraction number and overall treatment time to further reduce treatment burden of breast radiotherapy as much as possible. The FAST Forward trial [9] is a practice-changing study, testing two ultrahypofractionated 1‑week schedules (26 and 27 Gy in 5 fractions) against a moderate fractionated 3‑week regimen of 40 Gy in 15 fractions. The 10-year outcomes were recently presented at ESTRO 2025 (abstract only, no full publication). Data confirmed low incidence of in breast tumour recurrence across all schedules (40 Gy: 3.6%; 27 Gy: 3%; 26 Gy: 2%). Overall survival and breast cancer-specific survival were comparable in all three treatment arms. Conferring late normal tissue effects, they found higher rates of firmness, shrinkage, and induration with 27 Gy total dose, but comparable results with 40 and 26 Gy total dose. Patient-reported outcomes (breast symptoms, appearance, swelling) were very similar with 26 and 40 Gy but slightly worse with 27 Gy. Full publication of the data is awaited, but a 1-week radiotherapy regimen with 26 Gy total dose in 5 fractions is increasingly being established as the new standard for whole breast irradiation, chest wall irradiation and partial breast irradiation. Results for ultrahypofractionated nodal irradiation are promising but too short-term [10, 11] to declare it as standard therapy.

The rationale for partial breast irradiation (PBI), radiation focused on the former tumour bed including a safety margin, compared to conventional whole breast irradiation (WBI) is based on the finding that most recurrences arise near the primary tumour location. Multiple prospective randomised trials in more than 15,000 patients, using different techniques as interstitial brachytherapy [12, 13], external beam radiotherapy [14, 15] and intraoperative radiotherapy (IORT) [16, 17], have demonstrated oncologic equivalence between PBI and WBI with mostly no significant difference on local control. What we have learned from these trials is that PBI has significantly higher breast tumour recurrences (IBR) when delivered by IORT (TARGIT trial 0.95% vs 2.11%, ELIOT trial 2.4% vs. 12.6%), or older techniques using external beam RT without CT-based planning. But there was no significant effect on disease-free (DFS) or overall survival (OS). Concerning acute, long-term side effects and cosmesis PBI is associated with less acute toxicity, but with no significant difference in late toxicity and cosmesis except in the RAPID trial. The trial from Whelan et al., using external beam radiotherapy for PBI but with 2 fractions per day, demonstrated significant more moderate late toxicity and adverse cosmesis. The key to safe application of PBI is correct patient selection. Selection criteria are already published in several international guidelines. Suitable patient for tailored PBI is a low-risk patient, > 50 years of age, with small tumours (< 3 cm), unifocal und unicentric, negative lymph node status and clear resection margins (> 2 mm) [18]. For better identification of the former tumour bed, clip marking is mandatory for accurate computed tomography (CT)-based planning.

With the raising use of mammography, the incidence of ductal carcinoma in situ (DCIS) has increased significantly. While mastectomy was the standard surgical procedure for treatment of DCIS for decades, many patients now receive breast-conserving surgery. The need for adjuvant radiotherapy after breast-conserving treatment for DCIS is widely debated because of absolute benefit and possible side effects. Several randomized trials demonstrate that radiotherapy after breast conserving surgery (BCS) reduces the risk of local recurrence by approximately 50% at 10 years and the improvement on local control concerns all types of DCIS, but with no significant effect on overall survival [19, 20]. The current challenge for treatment decision is to identify patients with the potential of their DCIS to recur as invasive cancer, which is associated with a higher risk of breast cancer mortality [19]. Different novel biomarker assays like the Oncotype DX DCIS (Genomic Health, Inc/ ©Exact Science Corporation, 5505 Endeavor Lane, Madison WI, USA) or the DCISionRT® (PreludeDx, Heathcare company, Laguna Hills, CA, USA) test are under development to assess the 10-year risk of DCIS returning or progressing to local invasive breast cancer for better decision-making whether adjuvant radiotherapy is needed. But prospective validation of these novel biomarker assays in DCIS is needed.

Tailored treatment approaches in low-risk breast cancer with favourable prognosis (luminal A breast cancer) remain a topic of ongoing debate, especially regarding the role of adjuvant radiotherapy. The current standard of treatment for low-risk patients after breast-conserving surgery is endocrine therapy and radiotherapy. However, an ongoing debate on de-escalation of radiotherapy is based on the outcomes of several older studies (ABCSG‑8, GALGB, PRIME II) [21‐23] and newer studies including multigene signatures (IDEA, LUMINA, PRECISION, PRIMETIME) [24, 25] on omitting radiotherapy in luminal A patients. In all these trials, radiotherapy has a significant effect on in breast recurrence but no significant effect on overall survival under strict condition of continuous endocrine therapy. Omitting different adjuvant therapies (endocrine therapy and radiotherapy) in tumours with excellent prognostic features is analysed in the BASO II trial showing local recurrence at 2.2% per annum for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments [26]. But not only adjuvant radiotherapy is a good option in de-escalation. An interim analysis (2-year follow-up) of the EUROPA trial [27], looking at low-risk patients after breast surgery with either adjuvant endocrine therapy or radiotherapy, shows a significantly better global health score and significantly fewer treatment-related adverse events in the radiotherapy group. A longer follow-up must be awaited. However, because radiotherapy always has a significant effect on local recurrence rates in DCIS and invasive breast cancer, omitting radiotherapy in low-risk patients should always be part of shared decision making with patients.