Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes
Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes
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DOI：
10.1200/jco.2008.18.1370
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发表时间：
2009-03-10
影响因子：
45.3
通讯作者：
Bernard, Philip S.
中科院分区：
文献类型：
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作者：
Parker, Joel S.;Mullins, Michael;Bernard, Philip S.
通过开发一种融合了基于基因表达的风险模型的乳腺癌预后标准和化学疗法益处的当前标准，该标准均包含基于基于基因表达的基于“内在”亚型腔内腔A，Luminal B，HER2-富集和基部类似于基础。使用来自189个原型样品的微阵列和定量逆转录酶聚合酶链反应数据开发了预测变量。评估了761例患者（无全身治疗）预后的测试组，并评估了133例患者的病理完全反应（PCR）对紫杉烷和蒽环类药物方案的预测（PCR）。归因于内在的亚型作为离散的实体（p = 2.26E） -12）在融合标准参数的多变量分析中保持显着（雌激素受体状态，组织学等级，肿瘤大小和节点状态）。使用固有的亚型和临床信息建立了用于节点阴性乳腺癌的预后模型。仅临床病理模型或单独的亚型模型，合并模型（亚型和肿瘤大小）的C-指数估计值是显着改善。内在亚型模型预测了新辅助化疗疗效，PCR的负预测值为97％。固有亚型的结论性诊断为乳腺癌患者的标准参数增加了明显的预后和预测信息。连续风险评分的预后特性对于节点阴性乳腺癌的管理具有价值。亚型和风险评分也可用于评估新辅助化学疗法功效的可能性。
PurposeTo improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression - based "intrinsic" subtypes luminal A, luminal B, HER2-enriched, and basal-like.MethodsA 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen.ResultsThe intrinsic subtypes as discrete entities showed prognostic significance ( P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%.ConclusionDiagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy.