Locoregional recurrence remained low over 10 years in patients with high-risk breast cancer who received shorter courses of radiotherapy after mastectomy in a phase 3 trial.

Among postmastectomy patients requiring regional nodal irradiation, hypofractionated radiotherapy and conventional fractionated radiotherapy showed comparable cumulative incidence of locoregional recurrence at 5 years (9.6% vs 8.6%), the primary endpoint of the trial. There were no significant differences in survival outcomes or increases in severe late adverse effects.

“These findings can give clinicians greater confidence in using shorter-course postmastectomy radiotherapy for appropriately selected patients with high-risk breast cancer. Wider adoption could reduce treatment burden for patients while also improving the efficiency and accessibility of radiotherapy services,” lead author Guang-Yi Sun, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, told Medscape Medical News.

The abstract was presented on September 28th at the American Society for Radiation Oncology (ASTRO) 2026 Annual Meeting, and the full study was published simultaneously in The Lancet Oncology.

The new work builds off the investigators’ previous 5-year study, which showed that hypofractionated postmastectomy radiotherapy was noninferior to conventional fractionated postmastectomy radiotherapy.

Long-term data for the efficacy and safety of hypofractionated postmastectomy radiotherapy with regional nodal irradiation is limited. In this latest study, the authors assessed the durability of disease control and adverse effects of the treatment regimen at 10 years.

The sample consisted of 820 women aged 18-75 years with high-risk breast cancer who had undergone modified radical mastectomy and axillary dissection. Of these, 810 were included in a modified intention-to-treat analysis.

The patients presented with T3-T4 primary tumors or at least four positive lymph nodes. Patients were randomly assigned in a 1:1 ratio to receive either hypofractionated postmastectomy radiotherapy (43.5 Gy in 15 fractions over 3 weeks) or conventional fractionated postmastectomy radiotherapy (delivered at 50 Gy in 25 fractions over 5 weeks) to the chest wall and supraclavicular region.

Patient 10-year outcomes were assessed in a descriptive analysis. Secondary outcomes included disease-free survival, overall survival, and late adverse events.

At 10 years, the locoregional recurrence rates were 10.3% with conventional fractionated postmastectomy radiotherapy and 12.0% with hypofractionated postmastectomy radiotherapy (hazard ratio, 1.19; 95% CI, 0.79-1.82). Most locoregional events involved the regional nodes, particularly in the supraclavicular region.

There were no significant differences in disease-free survival (65.2% with conventional fractionated postmastectomy radiotherapy vs 69.9% with hypofractionated postmastectomy radiotherapy) or overall survival (72.9% vs 77.5%). There were no grade 4-5 events, severe adverse effects, brachial plexopathy, or treatment-related deaths.

Overall, the most common grade 3 adverse effects were ischemic heart disease, lymphoedema, and skin or shoulder problems. Grade 1-2 pulmonary fibrosis was more common with hypofractionated postmastectomy radiotherapy (P = .008).

“Together with our previously reported 5-year results, these long-term data further support hypofractionated radiotherapy as a standard option for postmastectomy treatment that includes regional nodal irradiation,” Sun said.

Limitations of the study were that the trial was conducted at a single center and most patients were treated with two-dimensional radiotherapy rather than newer techniques. In addition, data on the patient’s race and ethnicity were not reported.

The results are an important confirmation that clinicians can continue to offer these convenient courses of radiation for patients, Janice Lyons, MD, study discussant, told Medscape Medical News.

“The patients where we need to take a step back and not necessarily adopt these moderately hypofractionated schedules is in the case of inflammatory breast cancer, where we’re taking things to a higher dose of radiation,” Lyons, professor of radiation oncology at University Hospitals Seidman Cancer Center/Case Western Reserve University in Cleveland, said. For those patients, conventional fractionation remains the standard of care.

Another challenge is that although there are now multiple studies that support hypofractionated radiotherapy in breast cancer, the dose used among studies differs, she noted. “I think we as a community need to be thoughtful on which fractionation schedules we use based on the patient that we’re seeing and their risk profile.”

An important next step is to assess even shorter schedules in patients requiring postmastectomy radiotherapy and regional nodal irradiation, using contemporary treatment techniques, Sun said.

Sun and Lyons reported having no relevant disclosures. The study was funded by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, the National Natural Science Foundation of China, the National High Level Hospital Clinical Research Funding, the Cooperation Fund of Cancer Hospital, the Chinese Academy of Medical Sciences (CAMS), and the CAMS Innovation Fund for Medical Sciences.