By POLAR.

Top Line: The decision to omit adjuvant radiation (or not) for low risk breast cancer has historically been informed by age, tumor size, grade, receptor status, and the assumption that 5+ years of endocrine therapy will be completed.

The Study: POLAR is a 16-gene signature prognostic of locoregional recurrence risk in patients with node negative, hormone receptor positive, HER2 negative breast cancer. In this study, it was developed using tissue from patients treated in the SweBCG91-RT trial. In the original SweBCG91-RT trial, 1178 patients with stage I-IIA, node negative breast cancer were randomized to +/- radiation after breast conservation surgery. A minority of patients received any form of adjuvant systemic therapy (offered to stage II patients). At 15 years, adjuvant radiation halved the risk of ipsilateral breast tumor recurrence (11.5% v 23.9%) and even improved the rate of recurrence free survival (60.4% v 51.7%). The authors of the original report could not identify a “low risk” subset of patients who did not benefit from adjuvant radiation. Indeed, other studies supporting the option to omit radiation for low risk patients still show a small but significant local control benefit to adjuvant radiation. Of the SweBCG91-RT participants, tissue from 597 patients (41% training cohort, 59% validation cohort) with HR+/HER2- breast cancer who did not receive adjuvant systemic therapy or endocrine therapy was used to develop the novel low risk genomic signature coined POLAR. POLAR was prognostic of locoregional recurrence risk among patients not treated with radiation independent of age, tumor size, and luminal A v luminal B status. In the validation cohort, 30.5% had a low risk score. Among low risk patients, there was no difference in LRR risk at 10 years with or without RT (5% v 6%). As a reminder, those patients didn’t receive adjuvant endocrine therapy either. Among high risk patients, adjuvant RT reduced LRR risk from 19% to 8%. You may recall the same group also developed the ARTIC classifier of higher risk disease that may benefit from radiation intensification. POLAR weakly correlates with ARTIC meaning the two provide different information and could be used together to define a spectrum of radiation benefit.

TBL: The POLAR genomic classifier identifies a low risk subset of breast cancer patients with node negative, HR+/HER2- disease with a low risk of recurrence after breast conservation surgery alone. | Sjostrom, J Clin Oncol 2022