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指导乳腺癌辅助治疗的临床和基因组风险 Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer 摘 要 背景 乳腺癌患者的辅助化疗可通过临床病理因素和用于确定复发风险的21基因检测评分来指导。目前尚不清楚乳腺癌复发的临床风险水平可否为复发评分增加预后信息。 方法 我们开展了一项前瞻性试验，试验纳入了9427例激素受体阳性、人表皮生长因子受体2阴性、腋窝淋巴结阴性且接受了21基因检测的女性乳腺癌患者，此外我们根据肿瘤大小和组织学分级将乳腺癌复发的临床风险分为低风险或高风险。我们采用Cox比例风险模型计算远处复发的风险比，以此评估临床风险产生的影响。大多数50岁或50岁以下绝经前女性的初始内分泌治疗是他莫昔芬单药治疗。 结果 临床风险水平对于以下女性患者的远处复发具有预后意义：21基因复发评分中等（11~25，评分范围为0~100，评分较高表示预后较差或接受化疗的潜在获益较大），被随机分配接受内分泌治疗（对高和低临床风险进行比较的风险比，2.73；95%置信区间[CI]，1.93~3.87）或被随机分配接受化疗联合内分泌（化学内分泌）治疗的女性患者（风险比，2.41；95% CI，1.66~3.48），以及复发评分高（26~100）的女性患者，这些患者全部被分配接受化学内分泌治疗（风险比，3.17；95% CI，1.94~5.19）。在仅接受内分泌治疗的50岁或50岁以下女性患者中，复发评分低（评分为0~10）的患者在9年时的远处复发率估计值（±SE）低于5%（≤1.8±0.9%），与临床风险无关，而复发评分中等且临床风险低的患者在9年时的远处复发率为4.7±1.0%。在这一年龄组中，临床风险高，复发评分中等且仅接受内分泌治疗的女性患者（12.3±2.4%），以及复发评分高且接受化学内分泌治疗的女性患者（15.2±3.3%）在9年时的远处复发率估计值超过10%。 结论 临床风险分层提供了预后信息，将其添加到21基因复发评分之后，可用于识别可从更有效治疗中获益的绝经前女性。（由美国国立癌症研究所等资助；在ClinicalTrials.gov注册号为NCT00310180。） Joseph A. Sparano, Robert J. Gray, Peter M. Ravdin, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. DOI: 10.1056/NEJMoa1904819 Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer 指导乳腺癌辅助治疗的临床和基因组风险 Abstract Background The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. Methods We performed a prospective trial involving 9427 women with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. Results The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). Conclusion Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.) Joseph A. Sparano, Robert J. Gray, Peter M. Ravdin, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. DOI: 10.1056/NEJMoa1904819 参考文献 [1] Sparano JA, Gray RJ, Ravdin PM, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med 2019. DOI: 10.1056/NEJMoa1904819 [Epub ahead of print]. [2] Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:2817-2826. [3] Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 2015;373:2005-2014. [4] Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 2018;379:111-121. 版权信息 |
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来自： 生物_医药_科研 > 《2019ASCO》
