文献速递 | 21基因检测揭示化疗对淋巴结阳性乳腺癌的益处

外科黄文斌 2022-03-04

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文章题目: 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer

研究人员：K. Kalinsky.et al.

研究单位：The Winship Cancer Institute at Emory University

发表时间：Dec 2021

期刊名称：N Engl J Med

影响因子：91.245

【1】核心亮点：

Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease–free survival and distant relapse–free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy.

在有1到3淋巴结阳性且复发评分为25分或更低的绝经前妇女中，接受化学内分泌治疗的妇女比只接受内分泌治疗的妇女有更长的侵袭性无病生存期和远处无复发生存期，而具有类似特征的绝经后妇女并未从辅助化疗中获益。

【2】思路与方法：

In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival.

在一项前瞻性试验中，我们随机分配患有激素受体阳性、HER2 阴性乳腺癌、1 到 3腋窝淋巴结阳性且复发评分为 25 或更低（评分范围为 0 至 100，评分越高表明预后较差）仅接受内分泌治疗或化疗加内分泌（化学内分泌）治疗。主要目的是确定化疗对侵袭性无病生存的影响，以及该影响是否受复发评分的影响。次要终点包括远处无复发生存。

【3】摘要：

Background: The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary lymph-node-negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear.

Methods: In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival.

Results: A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease-free survival differed according to menopausal status (P = 0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P = 0.89). Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002), with a similar increase in distant relapse-free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009). The relative chemotherapy benefit did not increase as the recurrence score increased.

Conclusions: Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease-free survival and distant relapse-free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy.

背景：基于21基因乳腺癌检测的复发评分在预测激素受体阳性、人表皮生长因子受体2（HER2）阴性、腋窝淋巴结阴性乳腺癌的化疗益处方面具有临床应用价值。在淋巴结疾病阳性的女性中，复发评分在预测辅助化疗益处方面的作用尚不清楚。

方法：在一项前瞻性试验中，我们随机将激素受体阳性、HER2阴性乳腺癌、一到三腋窝淋巴结阳性的女性，复发评分为25分或更低（评分范围为0到100分，评分越高，预后越差）的患者只能接受内分泌治疗或化疗加内分泌（化学内分泌）治疗。主要目的是确定化疗对侵袭性无病生存率的影响，以及这种影响是否受复发评分的影响。次要终点包括远处无复发生存率。

结果：共有5083名女性（33.2%的绝经前女性和66.8%的绝经后女性）接受了随机分组，5018人参与了试验。在预先指定的第三次中期分析中，化疗对增加侵袭性无病生存率的益处因绝经状态不同而不同（绝经前和绝经后参与者的化疗益处比较P=0.008），并进行了单独的预先指定分析。在绝经后妇女中，仅内分泌组和化学内分泌组的5年无创生存率分别为91.9%和91.3%，无化疗益处（侵袭性疾病复发、新发原发癌[乳腺癌或其他类型]或死亡的风险比为1.02；95%可信区间[CI]，0.82至1.26；P=0.89）。在绝经前妇女中，仅内分泌治疗的5年无创生存率为89.0%，化学内分泌治疗的5年无创生存率为93.9%（危险比，0.60；95%可信区间，0.43至0.83；P=0.002），无远处复发生存率也有类似的增加（危险比，0.58；95%可信区间，0.39至0.87；P=0.009）。随着复发评分的增加，相对化疗的益处没有增加。

结论：在有1到3淋巴结阳性且复发评分为25分或更低的绝经前妇女中，接受化学内分泌治疗的妇女比仅接受内分泌治疗的妇女有更长的侵袭性无病生存期和远处无复发生存期，而具有类似特征的绝经后妇女并未从辅助化疗中获益。

【4】图表：

图1：筛选、随机化和治疗。

Fig 1. Screening, Randomization, and Treatment.

表1：受试者基线特征。

Table 1. Baseline Characteristics of the Participants.

图2：在所有参与者中复发评分为25分或更低的参与者中，根据绝经状态(治疗意向人群)无侵袭性疾病和远距离无复发生存期。

Fig 2. Invasive Disease–free and Distant Relapse–free Survival among Participants with a Recurrence Score of 25 or Lower among All Participants and According to Menopausal Status (Intention-to-Treat Population).

图3：接受化学内分泌治疗或仅接受内分泌治疗的复发评分为25或更低的女性无侵袭性疾病生存率。

Fig 3. Invasive Disease–free Survival among Women with a Recurrence Score of 25 or Lower Who Received Chemoendocrine Therapy or Endocrine Therapy Only.