Loyola University Chicago Stritch School of Medicine, Division of Hematology/Oncology, Maywood, IL 60153, USA.
Breast. 2009 Oct;18 Suppl 3:S141-5. doi: 10.1016/S0960-9776(09)70290-5.
Multigene assays performed on the primary tumors from women with non-metastatic 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.
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.
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.
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.
对非转移性乳腺癌女性的原发性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出良好和不良的预后潜力。最近，进行了分析以确定这些检测是否可以预测哪些患者受益于内分泌治疗联合辅助化疗，反之，哪些患者因为缺乏实质性益处而可以避免化疗。本文献综述总结了这些数据，并对这些检测的局限性和临床实用性提供了一个观点。
调查了早期乳腺癌中多基因检测和特征的文献。仅分析了两种检测方法-21 基因复发评分（RS）检测（Oncotype DX）和 70 基因特征（MammaPrint）-在随机或非随机临床人群中，以确定该检测在激素受体阳性肿瘤患者的辅助化疗环境中的预测效用。这些数据按临床分析类型进行总结，提供了有关临床实用性和与标准临床病理因素的比较研究的信息。
从两项具有单独使用他莫昔芬的对照组的 III 期临床试验中的 2 项独立分析来看，21 基因 RS 检测定义了一组低评分的患者，他们似乎不会从化疗中获益，而另一组高评分的患者则从 CMF 或 CAF 化疗中获益较大。一项研究在淋巴结阴性疾病中进行，第二项研究在淋巴结阳性人群中进行。在这两项研究中，交互项均具有统计学意义，并且在调整其他标准因素后，该检测的效果仍然存在。在非随机临床环境中，70 基因特征也可以预测高危组的化疗获益，而低危组则没有明显获益，在调整标准因素后，这种效果仍然存在。对于这两种检测方法，检测预测与临床病理风险分类之间的不一致率约为 30％。临床实用性研究表明，在 25-30％的情况下，使用检测结果改变了治疗决策，最常见的是从化疗内分泌治疗改为内分泌治疗。
使用多基因检测确定的风险类别预测辅助化疗相对于内分泌治疗的获益在不同风险水平上有很大差异，这挑战了以前的辅助治疗模式，即获益程度与风险无关。这些数据证明了目前对这些检测的临床应用，而正在进行的前瞻性研究将进一步完善它们在实践中的作用。
