70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer
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DOI：
10.1056/nejmoa1602253
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发表时间：
2016-08-25
影响因子：
158.5
通讯作者：
Piccart, M.
中科院分区：
文献类型：
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作者：
Cardoso, F.;van't Veer, L. J.;Piccart, M.
70个基因签名测试（MammaPrint）已被证明可以改善早期乳腺癌女性临床结果的预测。我们试图提供前瞻性证据的临床效用的70个基因的签名，以标准的临床病理标准，在选择患者的辅助chemotherapy. METHODS在这个随机的，3期研究，我们招募了6693名妇女与早期乳腺癌，并确定他们的基因组风险（使用70个基因的签名）和他们的临床风险（使用修改版本的佐剂！在线）。低临床和基因组风险的妇女没有接受化疗，而高临床和基因组风险的妇女确实接受了这种治疗。在风险结果不一致的患者中，使用基因组风险或临床风险来确定化疗的使用。主要目的是评估在具有高风险临床特征和低风险基因表达谱且未接受化疗的患者中，无远处转移的5年生存率的95%置信区间的下限是否为92%（即，共有1550名患者（23.2%）被认为具有高临床风险和低基因组风险。在未接受化疗的患者中，5年无远处转移的生存率为94.7%（95%置信区间，92.5 - 96.2）。这些患者与接受化疗的患者之间的生存率绝对差异为1.5个百分点，未接受化疗的患者的生存率较低。在雌激素受体阳性、人表皮生长因子受体2阴性、淋巴结阴性或淋巴结阳性的患者亚组中，无远处转移的生存率相似。根据70个基因签名不接受化疗导致5年无远处转移的生存率比化疗低1.5个百分点。考虑到这些发现，大约46%的乳腺癌患者可能不需要化疗。（由欧盟委员会第六框架计划和其他机构资助; ClinicalTrials.gov编号，NCT 00433589; EudraCT编号，2005-002625-31。）
BACKGROUNDThe 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy.METHODSIn this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher.RESULTSA total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease.CONCLUSIONSAmong women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.)