Investigation of a prostate cancer radiation response signature in the breast cancer SweBCG91RT randomized trial
In brief
High PORTOS score halves recurrence risk from breast-conserving radiotherapy
In the SweBCG91RT trial, women with early-stage breast cancer in the top three-quarters of the 24-gene PORTOS signature experienced roughly a 50% lower 10-year recurrence rate when given whole-breast radiation (SHR 0.46). Lower-scoring patients derived little benefit, and higher scores were linked to more breast pain, suggesting the test may help tailor radiation decisions while highlighting a need to balance efficacy and toxicity.
- Journal
- Clinical cancer research : an official journal of the American Association for Cancer Research (Q1)
- Published
- 30 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Shuang G Zhao, Erik Holmberg, Dan Lundstedt, Fredrika Killander, Emma Niméus, Marina Sharifi, et al.
- PMID
- 42531378
- DOI
- 10.1158/1078-0432.CCR-26-1455
Why clinicians should know about it
Abstract
PURPOSE: PORTOS is a 24-gene radiation response signature developed and validated in multiple randomized trials in prostate cancer. Given its basis in general radiation and DNA damage response pathways, we sought to evaluate whether PORTOS could also predict RT benefit in breast cancer. METHODS: PORTOS scores were calculated from gene expression profiles of 765 tumor samples from SweBCG91RT, a randomized trial of adjuvant whole-breast RT versus observation following breast-conserving surgery in node-negative stage I-IIA breast cancer. The primary endpoint was 10-year cumulative incidence (CI) of any recurrence, which closely mirrored the prostate cancer endpoints PORTOS was validated on. Patient-reported breast pain and tumor-infiltrating leukocytes (TILs) were also analyzed. RESULTS: A significant interaction (P = 0.049) between PORTOS and RT was observed for 10-year CI of any recurrence. Patients in the top 75% of PORTOS scores derived substantial benefit from RT (subdistribution hazard ratio (SHR) = 0.46, P < 0.001), compared to those in the bottom 25% (SHR = 0.73, P = 0.24). Higher PORTOS scores were also associated with increased risk of RT-related breast pain, though the interaction P-value was not significant (interaction P = 0.07). PORTOS was weakly anti-correlated with tumor size, histologic grade, and TILs, and provided orthogonal information to previously validated signatures ARTIC and POLAR. CONCLUSION: PORTOS predicts benefit from RT for any recurrence in early-stage breast cancer, mirroring its performance in prostate cancer. It is the first radiation response biomarker to demonstrate predictive value for both efficacy and toxicity across randomized trials in multiple tumor types.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.