【进展】JAMA：新乳腺癌预测试验对治疗的指导

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May 13, 2011 — A new test might identify breast cancer patients who have a high probability of survival after taxane and anthracycline chemotherapy.
一项新的诊断试验可以将已接受紫杉烷与蒽环类抗生素化疗的高生存率的患者成功分辨出来。
According to findings from a study published in the May 11 issue of the Journal of the American Medical Association, a test for response to and survival after sequential chemotherapy for ERBB2-negative breast cancer predicted chemoresistance, chemosensitivity, and endocrine sensitivity.
根据《美国医药协会》5月11日刊载的一份研究，一项新的测试可以预测人表皮生长因子受体2阴性的患者在接受序贯化疗后的反应及生存率，判断其对化疗药是否敏感和激素敏感度。
After excluding patients with predicted endocrine sensitivity, the authors found that the chemopredictive test algorithm had a positive predictive value of 56% for pathologic response (complete pathologic response or residual cancer burden).
在排除激素敏感的病人后，本文作者发现此项检测对病理反应具有56%的阳性预测值（完全病理反应或残存瘤荷量）。
They also observed that in 28% of patients predicted to be sensitive to treatment, 3-year distant relapse-free survival (DRFS) was 92%, with a significant absolute risk reduction of 18%.
研究者同时发现有28%的患者被预测为对治疗敏感，他们的3年无远处复发生存率为92%，绝对危险度大幅下降18%。
Treatment sensitivity was predicted in 30% of patients in the estrogen receptor (ER)-positive phenotypic subgroup, and in 26% in the ER-negative subgroup. At 3 years, ER-positive patients achieved a DRFS of 97% and a significant absolute risk reduction of 11%.
在雌激素受体阳性表型的患者中，30%显示为对治疗敏感，而在雌激素受体阴性的患者，此指标为26%。在治疗的第3年，雌激素受体阳性患者获得97%的无远处复发生存率，绝对危险度大幅下降11%。
Patients with ER-negative cancer predicted to be sensitive to treatment had significantly improved 3-year DRFS (83%), an absolute risk reduction of 26%, and a positive predictive value for pathologic response of 83%.
在雌激素受体阴性的病人中，被预测为对治疗敏感的病人3年无远处复发生存率获得明显的提高（83%），绝对危险度下降26%，病理反应的阳性预测值为83%。
"Any test based on predicted sensitivity, resistance, or both to guide the selection of a standard adjuvant treatment regimen should predict a high probability of survival for patients predicted to be treatment sensitive . . . and a clinically meaningful survival difference between patients predicted to be treatment sensitive and insensitive. . . as well as improve on predictions using existing clinical pathological ***rmation," write the authors, who were led by Christos Hatzis, PhD, from Nuvera Biosciences Inc.
此项研究由来自Nuvera生物科技公司的Christos Hatzis博士领导。本文作者写道：“任何能预测治疗敏感性或耐药性以规范标准辅助治疗的试验都应该预测到对治疗敏感的患者具有更高的生存率。临床上，一项有意义检测应该能预测治疗敏感与耐药的患者的生存差异，并结合现有的临床病理学知识，提高这个预测的准确性。”
"The performance of our predictive test meets these criteria in an independent validation cohort," they add.
他们补充写道：“我们这个预测试验符合***有效的队列研究标准。”
Need for Predictive Tests
There is a clinical need for predictive tests for patients with newly diagnosed ERBB2-negative breast cancer who might benefit from chemotherapy, the authors note. Identifying patients who have a high probability of survival after receiving the current standard chemotherapy regimen and endocrine therapy, if warranted, would reaffirm that treatment decision.
临床上需要一项测试去预测被诊断为人表皮生长因子受体2阴性的乳腺癌患者接受化疗后的生存获益。区分此类接受标准化疗与激素治疗后具有高生存率的患者能进一步确定治疗方案。
Conversely, the authors write, the ability to identify patients with a significant risk for relapse, despite the use of chemotherapy, could be used to recommend participation in an appropriate clinical trial of potentially more effective treatment.
相反，如果能区分出接受化疗后仍然存在高复发风险的患者，则可以通过此项检测结果，推荐患者参加合适及更为有效的临床药物试验。
Identified Treatment Sensitivity and Survival
Dr. Hatzis and colleagues hypothesized that a predictive test to determine patient response to and survival after sequential taxane and anthracycline chemotherapy for ERBB2-negative breast cancer would account for each of the following biological characteristics: tumor phenotype, sensitivity to adjuvant endocrine therapy (if ER-positive), chemoresistance, and chemosensitivity.
Hatzis博士假设该项预测性试验能检测出患者在接受序贯紫杉烷与蒽环类化疗人表皮生长因子受体2阴性的乳腺癌患者治疗的敏感性与生存率，一些生物学特征包括肿瘤表型、辅助激素治疗敏感性（雌激素受体阳性患者）、化疗耐药性及化疗敏感性都可以得到很好的阐释。
The prospective multicenter study was conducted from June 2000 to March 2010 to develop a predictor of response to and survival after chemotherapy for patients with invasive breast cancer.
一份从2000年6月到2010年3月的前瞻性多中心研究试图找出患有进展性乳腺癌患者的化疗反应及化疗后生存率的预测因子。
In the discovery cohort, 227 biopsy samples were obtained, and all chemotherapy was administered as neoadjuvant treatment. In the validation group, 165 of 198 patients received all chemotherapy as neoadjuvant treatment.
发现队列（？）中，有227分活检样本被检测，所有化疗被作为新辅助化疗而处方。在确认组（？），198名中的165名患者接受了新辅助化疗。
The authors developed different predictive signatures for resistance and response to preoperative chemotherapy, which were derived from gene expression microarrays from newly diagnosed breast cancer patients (n = 310). Treatment sensitivity was predicted using the combination of signatures for sensitivity to endocrine therapy, chemoresistance, and chemosensitivity, with independent validation (198 patients) and comparison to other reported genomic predictors of chemotherapy response.
本文作者通过对新近被诊断为乳腺癌的患者（样本量为310人）的标本进行基因表达谱检测，找出了术前化疗耐药及反应不同的预测标签。治疗敏感性通过结合激素治疗敏感、化疗耐药及化疗敏感的基因表达标签、***确认组（？）（198名患者）及其他已报道的化疗反应基因组预测因子分析而得出。
Overall, they noted that there was a significant association between predicted sensitivity to treatment and improved DRFS (P = .002). The diagnostic likelihood ratio for disease occurrence, compared with the absence of 3-year distant relapse or death, if patients were predicted to be treatment sensitive, was 0.33 (95% confidence interval, 0.07 to 0.72).
总体上，本试验预测的治疗敏感性与无远处复发生存率的提高存在显著的相关性（P = .002）。对于被预测为治疗敏感的患者，与3年无远处复发或死亡相比，疾病发生诊断似然比为0.33（95%置信区间为0.07到0.72）.
The authors point out that the 3-year DRFS in patients who were predicted to be sensitive to treatment at the time of their diagnosis was similar to the 3-year DRFS of 93% in the 21% of patients who achieved complete pathologic response after a regimen of neoadjuvant chemotherapy.
本文作者指出，接受新辅助化疗后获得完全病理反应的21%的患者的3年无远处复发生存率为93%，在得到临床诊断时被预测为治疗敏感的患者的3年无远处复发生存率与之相似。
The 3-year DRFS for patients predicted to be insensitive to treatment was identical to the 3-year DRFS of 75% observed in those with residual disease.
被诊断为对治疗不敏感的患者，其3年无远处复发生存率与带瘤生存的患者的3年无远处复发生存率相似，为75%。
There was no association between predicted treatment sensitivity/DRFS and the type of taxane therapy administered. Genomic predictions were independently and significantly associated with risk for distant relapse or death (sensitive vs insensitive; hazard ratio, 0.19; P = .002) after the data were adjusted for standard clinical and pathologic parameters.
治疗敏感性或无远处复发生存率预测值与紫杉烷药物种类之间不存在相关性。相关数据在经过临床及病理参数标准校正后，基因组预测与远处复发或死亡风险存在***而显著的相关性（敏感与不敏感的危险比为0.19，P = .002）。
When the genomic prediction was added to a multivariate Cox model, the predictive utility of the model significantly increased. In this model, higher clinical tumor stage and ER-negative status were associated with a statistically significantly greater risk for distant relapse or death.
当基因组预测放到多变量Cox模型中时，模型的预测能力显著提升。在此模型中，更高的临床肿瘤分级及雌激素受体阴性与远处复发或死亡存在具有显著统计学差异的相关性。
The authors note that a predictive test with the performance observed in this study could potentially assist clinical decision-making and identify patients with stage II to III ER-positive and ERBB2-negative breast cancer who have excellent 3-year and 5-year DRFS (97%) after standard adjuvant treatment. But they conclude that it is "imperative to continue to evaluate the predictive accuracy of this test in additional validation studies."
本文作者注意到，此项研究中预测试验可以帮助医生作出临床抉择，分辨出被诊断为II 期到III 期雌激素受体阳性、人表皮生长因子受体2阴性、在接受标准辅助治疗后能获得良好（97%）3年及5年无远处复发生存率的乳腺癌患者。 然而，他们总结道：“此项试验的预测准确性尚需要确定性研究来进一步评估。”