美国埃默里大学Winship癌症研究所Kevin Kalinsky团队研究了21-基因检测提示淋巴结阳性乳腺癌化疗的益处。相关论文于2021年12月1日发表在《新英格兰医学杂志》上。

基于21-基因乳腺癌检测的复发评分已被临床用于预测激素受体阳性、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。在淋巴结阳性的女性中，复发评分在预测辅助化疗益处方面的作用尚不明确。

在一项前瞻性试验中，研究组随机分配激素受体阳性、HER2阴性乳腺癌、1-3个腋窝淋巴结阳性、复发评分为25分或更低（评分范围为0到100分，评分更高表示预后较差）的女性仅接受内分泌治疗或化疗加内分泌治疗。主要结局为探讨化疗对无侵袭生存率的影响，以及化疗效果是否受复发评分的影响。次要终点包括无远端复发生存率。

共有5083名女性（33.2%绝经前和66.8%绝经后）接受随机分组，5018名参加了试验。在预定的第三期中期分析中，化疗对增加无侵袭性疾病生存期的益处因绝经期不同而不同（绝经前和绝经后参与者的化疗益处相比有统计学差异），并分别进行了预定的分析。

在绝经后妇女中，单纯内分泌组5年无侵袭性疾病生存率为91.9%，化疗加内分泌组为91.3%，化疗并无益处，侵袭性疾病复发、新发原发癌症或死亡的危险比为1.02。在绝经前妇女中，化疗加内分泌组的5年无侵袭性生存率为93.9%，显著高于单纯内分泌组的89.0%，危险比为0.60；远端无复发生存率也有相似的增加，危险比为0.58。随着复发率的增加，相对化疗的益处没有增加。

研究结果表明，在1～3个淋巴结阳性、复发评分为25分或以下的绝经前妇女中，接受化疗加内分泌治疗的女性比单纯内分泌治疗的女性有更长的无侵袭性疾病生存期和远端无复发生存期。而绝经后具有类似特征的妇女则未能从辅助化疗中获益。

附：英文原文

Title: 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer

Author: Kevin Kalinsky, M.D.,, William E. Barlow, Ph.D.,, Julie R. Gralow, M.D.,, Funda Meric-Bernstam, M.D.,, Kathy S. Albain, M.D.,, Daniel F. Hayes, M.D.,, Nancy U. Lin, M.D.,, Edith A. Perez, M.D.,, Lori J. Goldstein, M.D.,, Stephen K.L. Chia, M.D.,, Sukhbinder Dhesy-Thind, M.D.,, Priya Rastogi, M.D.,, Emilio Alba, M.D., Ph.D.,, Suzette Delaloge, M.D.,, Miguel Martin, M.D.,, Catherine M. Kelly, M.B.,, Manuel Ruiz-Borrego, M.D.,, Miguel Gil-Gil, M.D.,, Claudia H. Arce-Salinas, M.D.,, Etienne G.C. Brain, M.D., Ph.D.,, Eun-Sook Lee, M.D.,, Jean-Yves Pierga, M.D., Ph.D.,, Begoa Bermejo, M.D.,, Manuel Ramos-Vazquez, M.D., Ph.D.,, Kyung-Hae Jung, M.D., Ph.D.,, Jean-Marc Ferrero, M.D.,, Anne F. Schott, M.D.,, Steven Shak, M.D.,, Priyanka Sharma, M.D.,, Danika L. Lew, M.A.,, Jieling Miao, M.S.,, Debasish Tripathy, M.D.,, Lajos Pusztai, M.D., Ph.D.,, and Gabriel N. Hortobagyi, M.D.

Issue&Volume: 2021-12-01

Abstract:

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.

DOI: 10.1056/NEJMoa2108873

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2108873

The New England Journal of Medicine：《新英格兰医学杂志》，创刊于1812年。隶属于美国麻省医学协会，最新IF：70.67 官方网址：http://www.nejm.org/ 投稿链接：http://www.nejm.org/page/author-center/home