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Meta-Analysis
. 2025 Mar 1;117(3):486-495.
doi: 10.1093/jnci/djae262.

Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis

Per Karlsson  1   2 , Anthony Fyles  3 , S Laura Chang  4 , Bradley Arrick  4 , Frederick L Baehner  4 , Per Malmström  5   6 , Mårtin Fernö  5 , Erik Holmberg  1 , Martin Sjöström  5   7 , Fei-Fei Liu  3 , David A Cameron  8   9 , Linda J Williams  9 , John M S Bartlett  8 , Joanna Dunlop  10 , Jacqueline Caldwell  10 , Joseph F Loane  11 , Elizabeth Mallon  11 , Tammy Piper  8 , Ian Kunkler  8 , Felix Y Feng  7 , Corey W Speers  12 , Lori J Pierce  13 , John P Bennett  4 , Karen J Taylor  8
Affiliations
Meta-Analysis

Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis

Per Karlsson et al. J Natl Cancer Inst. .

Abstract

Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low-risk cancers where RT will not further reduce recurrence rates.

Methods: An individual participant data meta-analysis was performed in 623 patients of node-negative estrogen receptor-positive and HER2-negative early breast cancer enrolled in 3 RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence was used to test the interaction between POLAR score and RT.

Results: A total of 429 (69%) patients' tumors had a high POLAR score, and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of locoregional recurrence (20%, 95% confidence interval [CI] = 15% to 26%, vs 5%, [CI] 2% to 11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT = 0.37, 95% CI = 0.23 to 0.60; P < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR = 0.92, 95% CI = 0.42 to 2.02; P = .832). The test for interaction between RT and POLAR was statistically significant (P = .022).

Conclusions: POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from RT in selected patients. Patients aged 50 years and older with estrogen receptor-positive and HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.

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Figures

Figure 1.
Figure 1.
Cumulative incidence of locoregional recurrence within 10 years for each treatment arm by POLAR risk group in 194 POLAR low (A) and 429 POLAR high (B). 95% confidence intervals for hazard ratios and cumulative incidences are given in parentheses. CI = confidence interval; Cum. inc. = cumulative incidence; HR = hazard ratio; POLAR = Profile for the Omission of Local Adjuvant Radiation; RT = radiation therapy.
Figure 2.
Figure 2.
Hazard ratios for Profile for the Omission of Local Adjuvant Radiation (POLAR) x radiotherapy interaction. The meta-analysis hazard ratio was statistically significant (P = .022). CI = confidence interval; HR = hazard ratio; n/N = number of locoregional recurrences/number of participants.
Figure 3.
Figure 3.
Likelihood of locoregional recurrence at 10 years as a continuous function of the POLAR score percentile for the RT and no RT treatment groups (n = 623). Shaded areas indicate 95% confidence intervals. LRR = locoregional recurrence; POLAR = Profile for the Omission of Local Adjuvant Radiation; RT = radiation therapy
See this image and copyright information in PMC

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