Validation of the POLAR breast cancer assay for radiotherapy omission: individual participant data meta-analysis

There are currently no molecular tests to identify individual breast cancer 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. Individual participant data meta-analysis of three randomized trials of RT in node-negative ER+/HER2- early breast cancer was carried out to validate POLAR. Among 623 patients with sufficient tumor material for analysis 429 (69%) had a high POLAR score and 194 (31%) had a low POLAR score. In the absence of RT, patients with a high POLAR score had a 10-year cumulative incidence of locoregional recurrence (LRR) of 20% (95% CI 15-26) compared with 5% (2-11) for those with a low POLAR score. Patients with a high POLAR score had a large benefit from RT (versus no RT: HR 0.37; p<0.001) whereas patients with a low POLAR score had no evidence of benefit form RT (0.92; p=0.832). The test for interaction between RT and POLAR was statistically significant (p=0.022). The authors conclude that POLAR is prognostic for LRR and predictive of benefit from RT in selected patients.