Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype
Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype
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DOI：
10.1200/jco.2015.63.1010
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发表时间：
2017-04-01
影响因子：
45.3
通讯作者：
Hortobagyi, Gabriel N.
中科院分区：
文献类型：
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作者：
Symmans, W. Fraser;Wei, Caimiao;Hortobagyi, Gabriel N.
目的探讨乳腺癌新辅助化疗后与残留癌负荷(RCB)相关的各表型亚型的长期预后，以及联合HER2靶向治疗后的长期预后。方法采用病理学方法，测量连续RCB指数(病理完全应答为RCB=0；残留病分为三种预定义的RCB指数[RCB-I、RCB-II和RCB-III])和YP分期的残留病。前瞻性观察患者的生存情况。三个患者队列接受紫杉醇(T)、氟尿嘧啶、阿霉素和环磷酰胺(T/FAC)治疗：原始开发队列(T/FAC-1)、验证队列(T/FAC-2)和独立验证队列(T/FAC-3)。另一个验证队列仅接受FAC化疗，第五个队列同时接受曲妥珠单抗(H)、紫杉醇、氟尿嘧啶、表阿霉素和环磷酰胺(FEC；H+T/FEC)序贯治疗。根据诊断时激素受体(HR)和HER2状态定义表型亚群，分为HR阳性/HER2阴性、HER2阳性(HR阴性/HER2阳性或HR阳性/HER2阳性)或三重受体阴性。结果5个队列(T/FAC-1[n=219]、T/FAC-2[n=262]、T/FAC-3[n=342]、FAC[132]和H+T/FEC[n=203])的中位无事件随访期分别为13.5年、9.1年、6.8年、16.4年和7.1年。连续的RCB指数在每个表型亚组中预测预后，与其他临床病理变量无关。RCB分类在总体上、在每个表型子集内和在YP分期类别内对预后风险进行分层。四种RCB(病理完全缓解、RCB-I、RCB-II和RCB-III)的10年无复发生存率在三受体阴性组分别为86%、81%、55%和23%；在T/FAC联合队列中HR阳性/HER2阴性组为83%、97%、74%和52%；在H+T/FEC队列中为95%、77%、47%和21%。我们的机构调查结果应该得到外部验证。(C)2017年美国临床肿瘤学会
PurposeTo determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)-targeted treatment.MethodsWe conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor-negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test.ResultsFive cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor-negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort.ConclusionRCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated. (C) 2017 by American Society of Clinical Oncology