How much radiotherapy is enough? Which patients can safely receive less treatment? And how can new technologies and systemic therapies change the way radiotherapy is delivered?
These questions continue to shape radiotherapy of breast cancer in 2026, as new studies examine treatment approaches that have long been part of routine clinical practice.
Several recent publications address important areas of uncertainty. ESTRO recommendations explore the potential role of radiotherapy before breast surgery, while new data examine whether regional nodal irradiation is necessary for every patient with residual nodal disease after neoadjuvant chemotherapy.
Other studies focus on treatment safety. Six-year follow-up data raise questions about the long-term cardiac effects of breast irradiation, and a joint ESMO–ESTRO consensus addresses the increasingly common challenge of combining radiotherapy with targeted systemic treatments.
There is also new evidence to inform breast conservation decisions in young women carrying BRCA1/2 mutations, alongside real-world data on the use of knowledge-based VMAT to improve treatment planning and limit radiation exposure to healthy tissues.
Not all of these findings are ready to change clinical practice. Some support existing approaches, while others identify areas where further research is needed.
In this edition, we look at six recent publications and what they tell us about the current direction of breast cancer radiotherapy.
ESTRO and ASTRO Address the Future of Preoperative Radiotherapy in Breast Cancer
The traditional sequence of breast cancer treatment, with radiotherapy delivered after surgery, may change as new evidence explores the potential benefits of preoperative irradiation.
In recommendations published in Radiotherapy and Oncology and endorsed by ASTRO, the European Society for Radiotherapy and Oncology (ESTRO) examines the current evidence and future role of preoperative radiotherapy in breast cancer.
The expert panel reviewed 27 phase I and II studies, investigating preoperative radiotherapy across different clinical settings, including early-stage low-risk disease, high-risk and locally advanced breast cancer, and patients requiring mastectomy and breast reconstruction.
In early-stage breast cancer, preoperative partial breast irradiation may improve target delineation, reduce treatment volumes, and potentially support future strategies involving surgery omission. Studies involving more than 300 patients reported generally favorable feasibility and cosmetic outcomes, although long-term oncologic evidence remains limited.
For high-risk breast cancer, preoperative radiotherapy combined with systemic therapy demonstrated pathological complete response rates ranging from 4.3% to 60.7%, with rates reaching 71% in triple-negative breast cancer in one study. In selected patients with initially unresectable disease, conversion to resectability ranged from 75% to 88.1% across three studies.
Another emerging application involves delivering radiotherapy before mastectomy to facilitate immediate breast reconstruction and potentially reduce complications associated with irradiating reconstructed tissue.
However, ESTRO emphasizes that preoperative radiotherapy remains investigational in most breast cancer settings. Current evidence is limited by small study populations, heterogeneous treatment schedules, and insufficient randomized comparisons.
The recommendations call for prospective trials to establish optimal dose and fractionation, treatment sequencing, integration with systemic therapies, and long-term oncologic and cosmetic outcomes.
Preoperative radiotherapy could eventually become an important component of personalized breast cancer treatment, but further evidence is needed before routine implementation.
Six-Year Study Reveals Persistent Cardiac Changes After Breast Cancer Radiotherapy
Long-term cardiac toxicity remains an important concern in breast cancer radiotherapy, particularly for patients receiving treatment to the left breast.
A prospective study published in Clinical and Translational Radiation Oncology investigated changes in cardiac function and biomarkers over six years following adjuvant breast radiotherapy, providing new evidence on the persistence of subclinical cardiovascular effects.
The study included 73 women with early-stage breast cancer, comprising 55 patients with left-sided disease and 18 with right-sided disease. All received adjuvant radiotherapy without chemotherapy, allowing researchers to examine cardiac changes without the additional cardiotoxic effects of chemotherapy.
Cardiac function was evaluated using echocardiography, while high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-brain natriuretic peptide (proBNP) were measured before radiotherapy and at three and six years after treatment.
After six years, median hscTnT increased from 4 to 6 ng/L, while proBNP rose from 78 to 118 ng/L (both p<0.001). The increase in troponin was particularly evident in patients with left-sided breast cancer and correlated with higher radiation doses to cardiac structures.
Echocardiographic assessments also identified persistent changes in left ventricular function. Among patients with left-sided disease, left ventricular ejection fraction declined from 65% to 60% (p=0.002), global longitudinal strain changed from −18% to −17% (p=0.006), and stroke volume decreased from 74 to 67 mL (p=0.015).
Changes in diastolic function were also observed, including impaired ventricular relaxation and reduced left atrial ejection fraction. Higher mean heart radiation dose and aromatase inhibitor use were associated with greater impairment in selected cardiac parameters.
Importantly, these abnormalities were already detectable at three years and persisted at six years, suggesting that some treatment-associated cardiac changes may be long-lasting.
The study was limited by its relatively small population, particularly the right-sided subgroup, and the absence of a nonirradiated control group, making it difficult to fully distinguish radiotherapy effects from aging and other cardiovascular risk factors.
The findings reinforce the importance of minimizing cardiac radiation exposure and considering long-term cardiovascular assessment in breast cancer survivors, particularly after left-sided radiotherapy. Sensitive echocardiographic measurements, including global longitudinal strain, together with cardiac biomarkers may help identify early changes before clinically apparent cardiac disease develops.
ESMO and ESTRO Define Safety Recommendations for Combining Radiotherapy With Targeted Cancer Therapies
As targeted therapies become increasingly integrated into breast cancer treatment, their safe combination with radiotherapy has become an important clinical consideration.
A new joint ESMO–ESTRO consensus published in Radiotherapy and Oncology provides evidence-based recommendations on combining radiotherapy with four major classes of targeted agents: CDK4/6 inhibitors, anti-HER2 monoclonal antibodies, PARP inhibitors, and mTOR inhibitors.
Although the recommendations apply across tumor types, they are particularly relevant to breast cancer, where these agents are frequently used alongside local and regional treatments.
The consensus was developed through systematic literature reviews and a modified Delphi process involving 18 international experts. Researchers screened 1,341 publications, included 107 studies, and evaluated 74 clinical scenarios according to drug class, irradiated anatomical region, and radiotherapy dose.
Agreement was reached on all 74 safety statements.
For anti-HER2 monoclonal antibodies, particularly trastuzumab and pertuzumab, the expected additional toxicity when combined with radiotherapy was generally low. The panel considered minor or no treatment adaptation appropriate for most clinical scenarios, including breast and thoracic irradiation. Nevertheless, cardiac toxicity remains an important consideration, especially in patients receiving left-sided breast radiotherapy.
In contrast, combining radiotherapy with CDK4/6 inhibitors, including palbociclib, ribociclib, and abemaciclib, requires greater caution. Although retrospective studies suggest that many combinations are feasible, reports of severe gastrointestinal toxicity have raised concerns. The experts recommended considering major treatment adaptations in most scenarios and avoiding concurrent treatment in selected high-dose irradiation settings involving the thorax, head and neck, or abdomen and pelvis.
For PARP inhibitors, including olaparib, the consensus recommended considering major treatment adaptations across all evaluated scenarios. These agents can increase radiosensitivity by interfering with DNA repair, potentially increasing hematologic, pulmonary, esophageal, and other treatment-related toxicities. Drug interruption or dose reduction may therefore be necessary depending on the clinical situation.
Similarly, mTOR inhibitors, such as everolimus, may increase radiation-associated toxicity. The panel recommended caution in most scenarios, particularly with high-dose thoracic radiotherapy because of concerns about pneumonitis.
Importantly, the recommendations distinguish between low-dose palliative radiotherapy, high-dose conventionally fractionated radiotherapy, and stereotactic radiotherapy, recognizing that treatment risks vary according to irradiated tissue, radiation dose, and the systemic agent involved.
The authors emphasize that evidence remains limited for several drug-radiotherapy combinations, particularly regarding long-term toxicity. The consensus statements are intended to support individualized multidisciplinary decisions rather than replace clinical judgment or prospective research.
The main clinical message is that the safety of combining radiotherapy with targeted therapy depends on the specific drug, irradiation site, and treatment intensity. While anti-HER2 monoclonal antibodies can generally be combined with radiotherapy with limited adaptation, CDK4/6, PARP, and mTOR inhibitors require more careful consideration of timing, dose modification, and potential overlapping toxicities.
Breast-Conserving Surgery and Radiotherapy Show Comparable Survival to Mastectomy in Young BRCA1/2 Carriers
Can young women with BRCA1/2 mutations safely choose breast-conserving surgery followed by radiotherapy instead of mastectomy?
A large international cohort study published in Radiotherapy and Oncology provides new evidence supporting breast conservation as a treatment option for selected young women carrying pathogenic BRCA1/2 variants.
The study, conducted through the BRCA BCY Collaboration, analyzed 4,837 women diagnosed with invasive breast cancer at age 40 or younger between 2000 and 2020. Researchers compared outcomes following breast-conserving surgery plus radiotherapy (BCS + RT), mastectomy alone, and mastectomy followed by radiotherapy.
Among participants, 1,704 (35.2%) received BCS + RT, 1,488 (30.8%) underwent mastectomy alone, and 1,645 (34.0%) received mastectomy plus radiotherapy. The median age at diagnosis was 35 years, and median follow-up was 8.2 years.
Overall survival was comparable between patients receiving BCS + RT and those undergoing mastectomy alone, with an adjusted hazard ratio of 1.02 (95% CI 0.78–1.34). Breast cancer-free interval was also similar between the two groups (adjusted HR 1.01, 95% CI 0.86–1.17).
However, breast conservation was associated with a higher risk of subsequent ipsilateral or contralateral breast cancer events compared with mastectomy alone (adjusted HR 1.33, 95% CI 1.07–1.66).
This association was particularly evident among BRCA1 carriers, who experienced a higher risk of subsequent breast events after BCS + RT (adjusted HR 1.64, 95% CI 1.24–2.16). In contrast, no statistically significant increase was observed among BRCA2 carriers (adjusted HR 0.86, 95% CI 0.61–1.23).
Despite these differences in subsequent breast cancer events, breast conservation was not associated with inferior overall survival.
The findings reinforce that BRCA mutation status alone should not automatically exclude breast-conserving treatment when clinically appropriate. Decisions should consider mutation type, tumor characteristics, long-term risk of additional breast cancers, surveillance requirements, and patient preferences.
The authors also emphasize the importance of early genetic testing, which may influence surgical planning and consideration of risk-reducing procedures.
However, the retrospective design, differences in disease characteristics between treatment groups, variation in genetic testing timing, and changes in treatment practices over two decades limit causal interpretation.
The study supports breast-conserving surgery followed by radiotherapy as a reasonable option for selected young BRCA1/2 carriers, while highlighting the need for individualized counseling about long-term recurrence risks and risk-reducing strategies.
Can Regional Nodal Irradiation Be Omitted in Breast Cancer With Residual Nodal Disease After Chemotherapy?
The possibility of reducing radiotherapy without compromising cancer outcomes is becoming an increasingly important topic in breast cancer treatment, particularly for patients receiving neoadjuvant chemotherapy.
A new multicenter retrospective study, KROG 21-06, published in Clinical and Translational Radiation Oncology, investigated whether regional nodal irradiation (RNI) can be safely omitted in selected patients who retain limited nodal disease after neoadjuvant chemotherapy.
The study included 245 patients with initially cT1–2N1 breast cancer treated at 12 institutions in South Korea between 2005 and 2017. All patients received neoadjuvant chemotherapy, underwent surgery with axillary lymph node dissection, and had one to three residual positive lymph nodes (ypN1). All received postoperative breast or chest wall radiotherapy, with or without regional nodal irradiation.
Among participants, 207 patients (84.5%) received RNI, while 38 (15.5%) did not. Median follow-up was 88.9 months, or approximately 7.4 years.
At five years, locoregional recurrence-free survival was 89.5% among patients receiving RNI compared with 97.2% among those who did not. Distant metastasis-free survival was 84.2% versus 91.6%, disease-free survival was 81.7% versus 91.6%, and overall survival was 91.1% versus 100%, respectively.
None of these differences reached statistical significance, and multivariable analysis did not identify RNI as independently associated with improved survival outcomes.
Instead, high histologic grade was associated with worse locoregional recurrence-free survival, while lymphatic invasion was independently associated with poorer distant metastasis-free survival.
The findings are particularly relevant because existing randomized evidence, including the NSABP B-51 trial, has supported RNI omission in patients who achieve complete nodal response (ypN0) after neoadjuvant chemotherapy. However, uncertainty remains for patients with residual nodal involvement.
KROG 21-06 extends the discussion to patients with limited residual nodal disease, suggesting that some individuals with ypN1 status following complete axillary dissection may not derive additional benefit from regional nodal irradiation.
Nevertheless, the results require cautious interpretation. The study was retrospective, only 38 patients omitted RNI, and treatment selection was not randomized. Patients receiving RNI more frequently had adverse pathological features, potentially influencing outcomes. Furthermore, all patients in the non-RNI group underwent breast-conserving surgery, limiting the applicability of the findings to patients treated with mastectomy.
The authors emphasize that larger prospective studies are needed before routine RNI omission can be established for this population.
The study adds to growing evidence supporting response-adapted radiotherapy after neoadjuvant chemotherapy, while highlighting the importance of considering residual nodal burden, tumor biology, pathological risk factors, and the extent of axillary surgery when individualizing treatment.
Knowledge-Based VMAT Achieves Low Heart and Lung Doses in Breast Cancer Radiotherapy
Modern radiotherapy techniques are increasingly focused on improving target coverage while minimizing radiation exposure to healthy organs, particularly the heart and lungs in patients receiving breast cancer treatment.
A new study published in Radiotherapy and Oncology evaluated the clinical performance of knowledge-based volumetric modulated arc therapy (VMAT), reporting favorable dosimetric outcomes and low acute toxicity in a large real-world breast cancer cohort.
Researchers at Royal North Shore Hospital in Sydney, Australia, retrospectively analyzed 484 patients treated between June 2020 and June 2023 using a standardized VMAT approach supported by knowledge-based planning (KBP).
The study included patients receiving breast or chest wall irradiation, with or without regional nodal irradiation, across conventional, hypofractionated, and ultrahypofractionated treatment schedules.
For patients receiving breast or chest wall irradiation alone, the median mean heart dose was 1.95 Gy with conventional fractionation, 1.03 Gy with hypofractionation, and 0.66 Gy with ultrahypofractionation.
Median mean ipsilateral lung doses were similarly low at 7.7 Gy, 5.22 Gy, and 3.56 Gy, respectively.
Importantly, favorable organ-at-risk dosimetry was also observed in patients requiring regional nodal irradiation, a setting where treatment planning is often more challenging because of the need to balance adequate target coverage with protection of nearby organs.
Target coverage was consistently high, with 99% of patients achieving delivery of at least 95% of the prescribed dose to 95% of the primary clinical target volume.
The study also reported favorable acute toxicity outcomes. No patients experienced clinician-reported grade 3 or higher toxicity. Grade 2 dermatitis occurred in 9% of patients, while 81% experienced grade 1 dermatitis.
No cases of radiotherapy-associated pneumonitis were reported, and 83% of patients experienced no clinically significant fatigue.
Knowledge-based planning was a central component of the treatment approach. By using previously developed high-quality treatment plans to generate personalized optimization objectives, KBP may improve planning consistency and reduce variation between planners.
The findings are particularly relevant as VMAT adoption in breast cancer radiotherapy has historically been limited by concerns regarding low-dose radiation exposure to healthy tissues, treatment complexity, and potential long-term toxicity.
However, the authors acknowledge that the retrospective, single-center design, absence of a conventional radiotherapy comparison group, and limited long-term follow-up prevent conclusions about superiority, late toxicity, or secondary cancer risk.
The study demonstrates that standardized knowledge-based VMAT can achieve excellent target coverage, low cardiac and pulmonary radiation doses, and favorable acute toxicity outcomes across a broad range of breast cancer treatment settings. These results support further evaluation and implementation of optimized VMAT workflows in breast radiotherapy.
