Prediction of adjuvant chemotherapy benefit in endocrine responsive, early breast cancer using multigene assays
Prediction of adjuvant chemotherapy benefit in endocrine responsive, early breast cancer using multigene assays
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DOI：
10.1016/s0960-9776(09)70290-5
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发表时间：
2009-10-01
期刊：
影响因子：
3.9
通讯作者：
van't Veer, Laura
中科院分区：
文献类型：
--
作者：
Albain, Kathy S.;Paik, Soonmyung;van't Veer, Laura
背景：对女性非转移性乳腺癌原发肿瘤进行多基因检测可提供有用的预后信息，并在不同的临床情况下区分好与坏的预后潜力。最近，研究人员进行了分析，以确定这些分析是否能预测哪些人从辅助化疗中获益于内分泌治疗，哪些人可能因为缺乏实质性的益处而避免化疗。这篇基于文献的综述总结了这些数据，并提供了这些分析的局限性和临床应用的观点。方法：查阅有关早期乳腺癌多基因检测和标记的文献。在随机或非随机临床人群中，只有两种检测方法——21基因复发评分（RS）检测（Oncotype DX）和70基因标记（MammaPrint）——进行了分析，以确定该检测方法在雌激素受体阳性患者的辅助化疗环境中的预测作用。这些数据按临床分析类型进行了总结，并与标准临床病理因素进行了临床应用和比较研究。结果：在他莫昔芬单独对照组的3期临床试验设置的2个独立分析中，21基因RS测定定义了一组评分低的患者，他们似乎没有从化疗中获益，第二组评分很高的患者从CMF或CAF化疗中获益。一项研究是在淋巴结阴性疾病中进行的，另一项是在淋巴结阳性人群中进行的。相互作用项在两项研究中都是显著的，并且在调整其他标准因素后，检测的效果仍然存在。利用非随机临床设置，70个基因标记也可以预测高风险组的化疗效果，而低风险组没有明显的益处，在调整标准因素后仍然存在这种效果。对于这两种检测，检测预测与临床病理风险类别之间的不一致性约为30%。临床效用研究表明，在25-30%的病例中，使用该检测会导致治疗决策的改变，最常见的是从化学内分泌治疗到单独的内分泌治疗。摘要：使用多基因检测确定的风险类别预测辅助化疗优于内分泌治疗的获益在不同的风险水平上差异很大，这挑战了以往的辅助治疗范式，即无论风险如何获益程度都是相同的。这些数据证明了这些分析目前的临床应用，而正在进行的前瞻性研究将完善其在实践环境中的作用。2009爱思唯尔有限公司版权所有。
Background: Multigene assays performed on the primary tumors from women with nonmetastatic breast cancer provide useful prognostic information and discriminate excellent versus poor outcome potential in diverse clinical scenarios. Recently, analyses were conducted to determine if these assays predict who benefits from adjuvant chemotherapy added to endocrine therapy and conversely, who might avoid chemotherapy because of lack of substantial benefit. This literature-based review summarizes these data and provides a perspective on the limitations and clinical utility of these assays.Methods: The literature regarding multigene assays and signatures in early breast cancer was surveyed. Only two assays - the 21-gene recurrence score (RS) assay (Oncotype DX) and the 70-gene signature (MammaPrint) - were analyzed in randomized or non-randomized clinical populations in order to determine the predictive utility of the test in the adjuvant chemotherapy setting in patients whose tumors were estrogen-receptor positive. These data are summarized by type of clinical analysis, with information on clinical utility and comparative studies with standard clinical-pathologic factors.Results: From 2 independent analyses in phase III clinical trial settings with tamoxifen-alone control arms, the 21-gene RS assay defines a group of patients with low scores who do not appear to benefit from chemotherapy, and a second group with very high scores who derive major benefit from CMF or CAF chemotherapy. One study was conducted in node-negative disease, and the second in a node-positive population. Interaction terms were significant in both studies, and the effect of the assay remained upon adjustment for other standard factors. Utilizing a non-randomized clinical setting, the 70-gene signature could also predict chemotherapy benefit in the high risk group, versus no apparent benefit in the low risk group, an effect that remained after adjustment for standard factors. For both assays, the discordance rate between the assay prediction and clinical-pathologic risk category was approximately 30%. Clinical utility studies showed use of the assay results in a change in treatment decision in 25-30% of cases, most commonly from chemoendocrine therapy to endocrine therapy alone.Summary: The prediction of adjuvant chemotherapy benefit over and above endocrine therapy using multigene assay-determined risk category differs greatly across risk level and challenges the previous adjuvant therapy paradigm that degree of benefit is the same regardless of risk. These data justify current clinical use of these assays, while ongoing prospective studies will refine their role in practice settings. (C) 2009 Elsevier Ltd. All rights reserved.