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过去二十年来，人们越来越认识到肿瘤生物学对于乳腺癌结局的意义，以及术后辅助化疗对于乳腺癌不同分子亚型的不同获益作用，尤其近年来对于雌激素受体阳性乳腺癌患者的术后常规辅助化疗提出了质疑。2006年，荷兰癌症研究所通过人类基因组计划，首先发表并验证了预测雌激素受体阳性早期乳腺癌患者结局的70基因表达谱（MammaPrint），随后相继被全国和国际乳腺癌指南采纳。2012年，荷兰乳腺癌指南推荐对所有临床病理特征不佳（T2期I级、T1c期II级、所有III级）的淋巴结阳性患者和淋巴结阴性乳腺癌患者进行术后辅助化疗，并且首次推荐对恶性程度低或中等、无或少量淋巴结转移的雌激素受体阳性且HER2阴性乳腺癌患者进行70基因表达谱检测。2015年，圣加仑专家组首次对管腔A型（激素受体阳性且HER2阴性且Ki-67低或基因特征低风险）乳腺癌的常规化疗进行反思，从而质疑仅仅根据肿瘤大小和1～3个淋巴结转移进行化疗的标准。2016年，荷兰全国研究证实70基因表达谱检测与2011～2013年雌激素受体阳性且HER2阴性且无明显淋巴结转移乳腺癌化疗显著减少相关。 2019年6月17日，美国乳腺外科医师学会和肿瘤外科学会《肿瘤外科学报》在线发表荷兰综合癌症组织、乌得勒支医院、乌得勒支大学、圣安东尼斯医院、特文特大学的研究报告，对2013～2016年70基因表达谱用于雌激素受体阳性且HER2阴性早期乳腺癌术后辅助化疗简化时代的作用变化进行了回顾分析。 该人群研究通过荷兰癌症登记数据库，对2013年1月～2016年12月根据2012年荷兰乳腺癌指南接受70基因术后辅助化疗指导的6780例雌激素受体阳性HER2阴性原发单侧乳腺导管浸润癌术前未行新辅助化疗女性患者进行回顾分析。按指南和年龄划分，对术后辅助化疗时间变化趋势进行亚组分析。通过逻辑回归模型，评定70基因对化疗的影响。 结果，2013～2016年早期乳腺癌术后辅助化疗比例由49%减少至23%，70基因检测比例由24%增加至51%。 对于淋巴结阴性早期乳腺癌患者，70基因检测与术后辅助化疗比例减少无关（比值比：1.0，95%置信区间：0.86～1.17），未进行70基因检测的患者术后辅助化疗比例也减少。 对于淋巴结1a期早期乳腺癌患者，70基因检测与术后辅助化疗比例减少相关（比值比：0.21，95%置信区间：0.15～0.29）。 对于年龄<50岁、50～59岁的患者，70基因检测与术后辅助化疗比例减少一致（比值比：0.17、0.53，95%置信区间：0.13～0.23、0.43～0.65）。 因此，根据该人群研究结果，雌激素受体阳性乳腺癌术后辅助化疗比例显著减少，尤其对于淋巴结阳性和年轻患者，70基因检测与患者术后辅助化疗比例减少显著相关。 Ann Surg Oncol. 2019 Jun 17. [Epub ahead of print] The Changing Role of Gene-Expression Profiling in the Era of De-escalating Adjuvant Chemotherapy in Early-Stage Breast Cancer. J. E. C. van Steenhoven, A. Kuijer, K. Schreuder, S. G. Elias, P. J. van Diest, E. van der Wall, S. Siesling, T. van Dalen. Diakonessenhuis Utrecht, Utrecht, The Netherlands; University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; St. Antonius Hospital, Nieuwegein, The Netherlands; Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands; University of Twente, Enschede, The Netherlands. PURPOSE: We assessed the recent trends in the administration of adjuvant chemotherapy thereby evaluating the role of the 70-gene signature (70-GS) testing in decision-making in the systemic treatment of patients with lymph node negative (N0) and lymph node positive (N+) breast cancer. METHODS: Patients with a national guideline directed indication for 70-GS use treated between 2013 and 2016 were selected from the Netherlands Cancer Registry. Time trends in the administration of adjuvant chemotherapy were evaluated within guideline- and age-delineated subgroups. The influence of the 70-GS on chemotherapy use was assessed with logistic regression. RESULTS: During the study period, the overall administration of adjuvant chemotherapy decreased from 49 to 23% and 70-GS use increased from 24 to 51%. The 70-GS was not associated with a decreased likelihood for N0 patients to receive chemotherapy (odds ratio [OR] 1.0; 95% confidence interval [CI] 0.86-1.17), as the proportion of N0 patients who received chemotherapy in the absence of 70-GS use decreased during the study period. In patients with N1a disease, 70-GS testing was associated with a decreased likelihood to receive chemotherapy (OR 0.21; 95% CI 0.15-0.29). In patients < 50 years and 50-59 years of age, 70-GS use was associated with a consistent lower proportion of patients receiving chemotherapy throughout the study period (OR 0.17; 95% CI 0.13-0.23 and OR 0.53; 95% CI 0.43-0.65, respectively). CONCLUSIONS: In this population-based study, the administration of adjuvant chemotherapy in ER+ breast cancer strongly declined. For node-positive and younger patients, 70-GS use was associated with a decreased probability for patients to receive adjuvant chemotherapy. DOI: 10.1245/s10434-019-07511-8 |
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