Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
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DOI：
10.1056/nejmoa1510764
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发表时间：
2015-11-19
期刊：
影响因子：
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通讯作者：
Sledge GW
中科院分区：
文献类型：
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作者：
Sparano JA;Gray RJ;Makower DF;Pritchard KI;Albain KS;Hayes DF;Geyer CE Jr;Dees EC;Perez EA;Olson JA Jr;Zujewski J;Lively T;Badve SS;Saphner TJ;Wagner LI;Whelan TJ;Ellis MJ;Paik S;Wood WC;Ravdin P;Keane MM;Gomez Moreno HL;Reddy PS;Goggins TF;Mayer IA;Brufsky AM;Toppmeyer DL;Kaklamani VG;Atkins JN;Berenberg JL;Sledge GW
先前使用包括档案肿瘤样本的前瞻性 - 回顾性设计的研究表明，基因表达分析提供了有临床价值的预后信息。然而，在接受统一治疗的人群中进行的前瞻性研究为生物标志物的临床有效性和实用性提供了最高水平的证据。
我们进行了一项前瞻性试验，涉及激素受体阳性、人表皮生长因子受体2型（HER2）阴性、腋窝淋巴结阴性的乳腺癌女性，肿瘤最大径为1.1至5.0厘米（或最大径为0.6至1.0厘米且肿瘤分级为中或高），这些患者根据临床病理特征符合考虑辅助化疗的既定指南。对石蜡包埋的肿瘤组织进行了21个基因的逆转录 - 聚合酶链反应分析，结果用于计算一个表明乳腺癌复发风险的评分；如果患者的复发评分为0至10，表明复发风险非常低（评分范围为0至100，分数越高表明复发风险越大），则被指定接受内分泌治疗而不进行化疗。
在招募的10253名符合条件的女性中，1626名（15.9%）复发评分为0至10的女性被指定仅接受内分泌治疗而不进行化疗。在5年时，在该患者人群中，无侵袭性疾病生存率为93.8%（95%置信区间[CI]，92.4%至94.9%），远处部位无乳腺癌复发率为99.3%（95% CI，98.7%至99.6%），远处或局部 - 区域部位无乳腺癌复发率为98.7%（95% CI，97.9%至99.2%），总生存率为98.0%（95% CI，97.1%至98.6%）。
在根据临床病理特征符合辅助化疗推荐既定指南的激素受体阳性、HER2阴性、腋窝淋巴结阴性的乳腺癌患者中，那些肿瘤具有良好基因表达谱的患者在仅接受内分泌治疗的情况下5年复发率非常低。（由美国国家癌症研究所及其他机构资助；ClinicalTrials.gov编号，NCT00310180）
Prior studies with the use of a prospective–retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. We performed a prospective trial involving women with hormone-receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative, axillary node–negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase–polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease–free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local–regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). Among patients with hormone-receptor–positive, HER2-negative, axillary node–negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.)