新辅助化疗后的病理完全缓解是一个独立的预测因素，与简化的乳腺癌内在亚型无关：来自EORTC 10994/BIG 1-00 III期试验的一项标志性和两步法分析
Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.
作者信息
Bonnefoi H, Litière S, Piccart M, MacGrogan G, Fumoleau P, Brain E, Petit T, Rouanet P, Jassem J, Moldovan C, Bodmer A, Zaman K, Cufer T, Campone M, Luporsi E, Malmström P, Werutsky G, Bogaerts J, Bergh J, Cameron D A
机构信息
Department of Medical Oncology, Institut Bergonié Comprehensive Cancer Centre, Université de Bordeaux, INSERM U916, Bordeaux, France
European Organisation for Research and Treatment of Cancer (EORTC), Brussels.
出版信息
Ann Oncol. 2014 Jun;25(6):1128-36. doi: 10.1093/annonc/mdu118. Epub 2014 Mar 11.
BACKGROUND
Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes.
PATIENTS AND METHODS
Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses.
RESULTS
Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1).
CONCLUSIONS
pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis.
CLINICALTRIALSGOV
EORTC 10994/BIG 1-00 Trial registration number NCT00017095.
背景
化疗后的病理完全缓解（pCR）与乳腺癌亚型及长期生存密切相关。在一项III期新辅助化疗试验中，我们试图确定pCR、TP53状态及治疗组（紫杉烷与非紫杉烷）对不同内在亚型患者的预后影响是否存在差异。
患者与方法
患者被随机分为接受六个周期的蒽环类化疗，或三个周期的多西他赛然后三个周期的表柔比星/多西他赛（T-ET）。pCR定义为原发肿瘤及淋巴结中无残余浸润性癌（或仅有极少散在肿瘤细胞）。我们采用了2011年圣加仑共识建议的简化内在亚型分类方法。使用标志性和两步法多变量分析研究pCR、TP53状态、治疗组和内在亚型对无事件生存（EFS）、无远处转移生存（DMFS）和总生存（OS）的相互作用。
结果
在随机分组的1856例患者中，有1212例（65%）可获得足够的pCR分析数据。1212例患者中有222例（18%）达到pCR：496例管腔A型中有37例（7.5%），147例管腔B/HER2阴性中有22例（15%），230例管腔B/HER2阳性中有51例（22%），118例HER2阳性/非管腔型中有43例（36%），221例三阴性（TN）中有69例（31%）。pCR对EFS的预后影响在各亚型间无差异，是EFS更好的独立预测因素[风险比（HR）=0.40，P<0.001，支持pCR]、DMFS（HR=0.32，P<0.001）和OS（HR=0.32，P<0.001）。化疗组仅对EFS是独立预测因素（HR=0.73，P=0.004，支持T-ET）。TP53、内在亚型与生存结局之间的相互作用仅在EFS方面接近统计学意义（P=0.1）。
结论
在两步多变量分析中，pCR是所有分子亚型良好临床结局的独立预测因素。
临床试验注册
欧洲癌症研究与治疗组织（EORTC）10994/国际乳腺癌研究组（BIG）1-00试验注册号NCT00017095 。
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