The 10-year results from the phase 3 CHN HYPOPMRT trial (NCT00793962) showed that hypofractionated postmastectomy radiotherapy (PMRT) delivered over 3 weeks maintained durable locoregional control compared with a conventional 5-week schedule among patients with high-risk breast cancer, according to results presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting.1
“The 3-year regimen met the original 5-year non-inferiority criterion, and maintained a low rate of locoregional recurrence through 10 years,” Guang-Yi Sun, of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, said during the presentation.1
At 10 years, the cumulative incidence of locoregional recurrence (LRR) was 12.0% with hypofractionated radiotherapy (HFRT) vs 10.3% with conventional fractionated radiotherapy (CFRT; HR, 1.19; 95% CI, 0.79-1.82). Investigators reported no significant differences between the arms in disease-free survival (DFS), overall survival (OS), or severe late toxicity.
According to the presentation, HFRT is well established in breast cancer, but most mature, randomized evidence comes from whole-breast irradiation following breast-conserving surgery. Because PMRT often encompasses both the chest wall and regional lymph nodes, evidence supporting a shorter schedule in this setting was limited when the trial began accruing in 2008. CHN HYPOPMRT was the first phase 3 trial to evaluate hypofractionated PMRT with regional nodal irradiation.
The trial’s initial 5-year analysis, published in Lancet Oncology in 2019, found the 3-week schedule to be noninferior to the 5-week schedule for LRR (8.3% vs 8.1%; HR, 1.10; 90% CI, 0.72-1.69; P for noninferiority <.0001). Grade 3 acute skin toxicity was also less frequent with HFRT (3% vs 8%; P <.001), while grade 3 pneumonitis rates were 3% and 2%, respectively.2
The single-center, open-label, randomized phase 3 trial enrolled women aged 18 to 75 years who had undergone modified radical mastectomy plus level I to II axillary lymph node dissection, had T3-4 or N2-3 disease, and had a Karnofsky performance score of at least 60. In total, 820 patients were randomly assigned 1:1 to CFRT at 50 Gy in 25 fractions over 5 weeks (n = 414) or HFRT at 43.5 Gy in 15 fractions over 3 weeks (n = 406); the modified intention-to-treat population included 409 and 401 patients, respectively. Treatment covered the chest wall and supraclavicular region, including the level III axilla, without irradiation of the internal mammary nodes (IMN) or level I to II axilla.
The primary end point was the 5-year cumulative incidence of LRR, with death treated as a competing event, and an absolute noninferiority margin of 5% (HR ≤1.883). Secondary end points included DFS, OS, and late radiation-related adverse events (AEs).
Patients had a median age of 49 years, 94% had stage III disease, and 33% had lymphovascular invasion. All patients received chemotherapy, and 77% of patients in the CFRT arm and 76% in the HFRT arm received hormonal therapy. Overall, 99% of patients received radiotherapy per protocol. At a median follow-up of 11.5 years, updated follow-up data were available for 734 of 810 patients (91%).
In the updated analysis, the 5-year HR for LRR was 1.13 (90% CI, 0.77-1.66). Most failures were regional. The 10-year local recurrence rates were 2.0% with CFRT vs 3.1% with HFRT (HR, 1.37; 95% CI, 0.57-3.25), and 10-year regional recurrence rates were 8.8% vs 9.9% (HR, 1.25; 95% CI, 0.81-1.93). Of 97 LRR events, 76 involved the regional nodes, with the supraclavicular region predominating.
The 10-year DFS rate was 69.9% (95% CI, 65.1%-74.2%) with HFRT vs 65.2% (5% CI, 60.3%-69.7%) with CFRT (HR, 0.87; 95% CI, 0.69-1.10; P = .24), and the 10-year OS rates were 77.5% (95% CI, 72.9%-81.4%) vs 72.9% (95% CI, 68.1%-77.1%), respectively (HR, 0.82; 95% CI, 0.63-1.08; P = .16). Investigators noted there was no evidence that the shorter regimen compromised long-term survival outcomes.
Severe late toxicity was uncommon, with no grade 4 or 5 events and no cases of brachial plexopathy. At 10 years, rates of grade 1, 2, and 3 lymphedemas were 21%, 5%, and 1% in the CFRT arm vs 20%, 4%, and less than 1% in the HFRT arm (P = .974), respectively. Late skin AEs, shoulder dysfunction, ischemic heart disease, and rib fracture were similar between arms. Grade 1 lung fibrosis was more common with HFRT (20% vs 12%; P = .008), although all cases were grade 1 and asymptomatic, and the protocol did not mandate routine CT surveillance. According to the investigators, increases in late AEs over the additional 5 years of follow-up were modest.
Sun placed the results alongside 2 other phase 3 trials, HypoG-01 (NCT03127995) and Skagen Trial 1 (NCT02384733), stating that 3 phase 3 trials now support a 3-week schedule when regional lymph nodes are treated. Unlike CHN HYPOPMRT, which used 2-dimensional radiotherapy without IMN irradiation, HypoG-01 (n = 1221) included IMN irradiation in 60% of patients and used intensity-modulated radiotherapy or 3-dimensional conformal radiotherapy, while Skagen Trial 1 (n = 2908) mostly included IMN irradiation. Both evaluated 40 Gy in 15 fractions vs 50 Gy in 25 fractions.
“Long-term results further establish hypofractionated PMRT with regional nodal irradiation as a standard of care for patients with high-risk breast cancer,” Sun concluded, adding that HFRT can improve patient convenience and health care efficiency without compromising long-term disease control or increasing late AEs.
References
Sun GY, Chen SY, Tang Y, et al. Hypofractionated vs. conventional fractionated postmastectomy radiotherapy in high-risk breast cancer (CHN HYPOPMRT): 10-year results. Presented at: 2026 American Society for Radiation Oncology Annual Meeting; September 26-30, 2026; Boston, MA.
Wang SL, Fang H, Song YW, et al. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2019;20(3):352-360. doi:10.1016/S1470-2045(18)30813-1.
