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Application of 21-gene Recurrence Score in Hormone Receptor Positive Breast Cancer Patients
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摘要: 近10年来，随着精准医疗的发展，乳腺癌的治疗进入了一个新时代，即在不影响生存结果的前提下，趋向于治疗降级、方案个体化，在给患者带来最大获益的同时尽可能减少医源性毒性暴露。21基因复发风险评分(21-gene recurrence score, RS)能够评估乳腺癌患者复发风险和化疗获益，已被美国临床肿瘤学会、美国国家综合癌症网络及中国抗癌协会推荐用于指导激素受体阳性、人类表皮生长因子受体2阴性的早期乳腺癌患者辅助治疗，但其临床应用尚存有争议。目前的研究主要聚焦于RS的临床优化，以更加准确地识别可从辅助治疗中受益的患者，使乳腺癌患者的治疗方案更加个体化。本文主要就RS在激素受体阳性乳腺癌患者辅助治疗中的应用、RS对临床决策的影响、RS面临的争议与应用前景等方面进行综述，以期指导临床进一步扩展RS的应用范围，使乳腺癌患者的辅助治疗更加精准。
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关键词:
- 乳腺癌 /
- 21基因复发风险评分 /
- 精准医疗 /
- 临床病理因素 /
- 辅助治疗
Abstract: In the past decade, with the introduction of precision medicine, the treatment of breast cancer has entered a new era. It now tends towards the de-escalation and individualization of treatment plans, aiming to minimize iatrogenic toxicity while maximizing benefits for patients without compromising survival outcomes. The 21-gene assay evaluates the expression levels of 21 genes associated with breast cancer recurrence and provides a 21-gene recurrence score (RS) to assess the risk of recurrence and potential benefit from chemotherapy in breast cancer patients. Currently, RS is recommended by multiple guidelines such as the American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), and Chinese Anti-Cancer Association(CACA) for guiding adjuvant therapy in hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer patients. However, there are still controversies surrounding its clinical application. Current research mainly focuses on optimizing RS to accurately identify patients who would benefit from adjuvant therapy, thus enabling more personalized treatment plans for breast cancer patients. This review provides an overview of the 21-gene assay, its application in HR+ breast cancer patients' adjuvant therapy, its impact on clinical decision-making, existing controversies regarding RS, and prospects for integrating RS with clinical pathological information. The aim is to guide further expansion of RS's application in clinical practice and achieve more precise adjuvant therapy for breast cancer patients.作者贡献：屈洋负责论文撰写、收集资料及论文构思；张燕娜负责收集资料及论文构思；周易冬、孙强负责论文构思及论文修订。利益冲突：所有作者均声明不存在利益冲突 -
表 1 RS指导HR+乳腺癌患者治疗的相关研究
分类 第一作者 发表时间
(年)试验名称/样本来源 患者例数
(例)患者类型 研究类型 RS分层标准 研究结论 RS在HR+/N0患者中的研究 Paik 2004[10] NSAPB-14 668 HR+、N0 回顾性研究 RS＜18、18≤RS＜31、RS≥31 RS可量化接受他莫昔芬治疗的HR+、N0乳腺癌患者远处复发的可能性 2006[22] NSAPB-20 651 HR+、N0 回顾性研究 RS＜18、18≤RS＜31、RS≥31 RS高危组从化疗中获益更多，低危组获益很小，中危组获益不明确 Sparano 2015[11] TAILORx 10 273 HR+/HER2-、N0 前瞻性研究 RS≤10、11≤RS＜25、RS≥26 RS≤10的HR+/HER2-、N0乳腺癌患者可安全豁免化疗 2018[6] 在RS中危组中，单独内分泌治疗与化疗联合内分泌治疗具有相似的疗效；仅RS为16~25且年龄≤50岁的年轻女性患者可从化疗中获益 2019[20] 临床风险分层提供了预后信息，当添加到RS中时，可更准确识别出能从化疗中受益的绝经前女性患者 RS在HR+/N+ 患者中的研究 Albain 2010[14] SWOG-8814 367 绝经后、HR+、N1~N2 回顾性研究 RS＜18、18≤RS＜31、RS≥31 腋窝淋巴结受累的RS低危组患者无法从蒽环类药物化疗中获益 Dowsett 2010[16] TransATAC 1372 绝经后、HR+、N0~N1 回顾性分研究 RS＜18、18≤RS＜31、RS≥31 在接受阿那曲唑和他莫昔芬治疗的HR+/N0~N1患者中，RS对于远处复发的预后价值相似 Gluz 2016[17] WGS PlanB 3198 HR+/HER2-、N0~N1 前瞻性研究 RS≤11、11＜RS≤25、RS＞25 对于RS低危组患者，即使通过传统临床病理因素被判定为高风险，豁免化疗后仍有5年无病生存期 Kalinsky 2021[18] RxPONDER 5018 HR+/HER2-、N1 前瞻性研究 RS≤25 RS≤25、HR+、N1绝经后女性患者可豁免化疗；而在绝经前女性患者中，辅助化疗可改善预后，且绝对获益随RS评分的增加而增加 RS：21基因复发风险评分；HR+：激素受体阳性；HER2-：人类表皮生长因子受体2阴性 
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