Karlsson Per, Fyles Anthony, Chang S Laura, Arrick Bradley, Baehner Frederick L, Malmström Per, Fernö Mårtin, Holmberg Erik, Sjöström Martin, Liu Fei-Fei, Cameron David A, Williams Linda J, Bartlett John M S, Dunlop Joanna, Caldwell Jacqueline, Loane Joseph F, Mallon Elizabeth, Piper Tammy, Kunkler Ian, Feng Felix Y, Speers Corey W, Pierce Lori J, Bennett John P, Taylor Karen J
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
Sahlgrenska Comprehensive Cancer Center, Sahlgrenska University Hospital, Gothenburg, Sweden.
J Natl Cancer Inst. 2025 Mar 1;117(3):486-495. doi: 10.1093/jnci/djae262.
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.
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.
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).
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.
目前尚无分子检测方法可识别放疗（RT）无获益的个体乳腺癌。局部辅助放疗省略概况（POLAR）是一种16基因分子特征，用于识别RT不会进一步降低复发率的低风险癌症。
对623例雌激素受体阳性、HER2阴性的早期乳腺癌且淋巴结阴性的患者进行个体参与者数据荟萃分析，这些患者参加了3项RT随机试验，其原发肿瘤材料可用于分析。使用Cox比例风险模型分析局部区域复发时间，以检验POLAR评分与RT之间的相互作用。
共有429例（69%）患者的肿瘤POLAR评分高，194例（31%）评分低。POLAR评分高的患者在未接受RT的情况下，10年局部区域复发累积发生率为20%（95%置信区间[CI]=15%至26%），而评分低的患者为5%（CI 2%至11%）。POLAR评分高的患者从RT中获益显著（RT与未RT的风险比[HR]=0.37，95%CI=0.23至0.60；P<0.001）。相比之下，没有证据表明POLAR评分低的患者从RT中获益（HR=0.92，95%CI=0.42至2.02；P=0.832）。RT与POLAR之间的相互作用检验具有统计学意义（P=0.022）。
POLAR不仅可预测局部区域复发，还能预测特定患者从RT中是否获益。年龄≥50岁、雌激素受体阳性、HER2阴性且POLAR评分低的患者可考虑省略辅助RT。需要在当代临床队列中进一步验证。
