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 cases of node-negative ER+/HER2-negative early breast cancer enrolled in three RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence (LRR) was used to test the interaction between POLAR score and RT. Results 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 LRR: 20% (15%-26%) vs 5% (2%-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 [0.23-0.60], p < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR: 0.92 [0.42-2.02], 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 radiotherapy in selected patients. Patients ≥ 50 years with ER+/HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.

中文翻译：

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乳腺癌检测对放疗遗漏的验证：个体参与者数据荟萃分析


背景 目前没有分子测试来识别放疗 （RT） 没有益处的个体乳腺癌。遗漏局部辅助放疗 （POLAR） 的概况是一种 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。方法 对 623 例淋巴结阴性 ER+/HER2 阴性早期乳腺癌病例进行个体参与者数据荟萃分析，这些病例纳入了 3 例 RT 随机试验，这些试验的原始肿瘤材料可用于分析。采用局部区域复发时间 （LRR） 的 Cox 比例风险模型来检验 POLAR 评分与 RT 之间的相互作用。结果 429 例 （69%） 患者的肿瘤 POLAR 评分高，194 例 （31%） 评分低。在没有 RT 的情况下，POLAR 评分高的患者有 LRR 的 10 年累积发生率：20% （15%-26%） vs 低评分患者的 5% （2%-11%）。POLAR 评分高的患者从 RT 中获益很大 （RT 与无 RT 的风险比 [HR]：0.37 [0.23-0.60]，p < .001）。相比之下，没有证据表明 RT 对 POLAR 评分低的患者有益 （HR： 0.92 [0.42-2.02]，p = .832）。RT 和 POLAR 之间相互作用的检验具有统计学意义 （p = .022）。结论 POLAR 不仅预后局部区域复发，而且可预测特定患者放疗获益。≥ 50 岁 ER+/HER2 阴性疾病且 POLAR 评分较低的患者可以考虑省略辅助放疗。需要在当代临床队列中进一步验证。