Medical Oncology Department, Institut Curie, PSL Research University, Paris, France.
Biostatistics Department, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, Marseille.
Ann Oncol. 2017 Jan 1;28(1):103-109. doi: 10.1093/annonc/mdw535.
We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab.
Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System.
From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value.
In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials.
我们对接受新辅助化疗联合贝伐珠单抗新辅助和辅助治疗的炎性乳腺癌（IBC）患者的两项前瞻性试验中的循环肿瘤细胞（CTC）和循环内皮细胞（CEC）的预测和预后价值进行了汇总分析。
非转移性 T4d 患者入组两项 II 期多中心试验，评估贝伐珠单抗联合曲妥珠单抗在 HER2 阳性肿瘤中的疗效（BEVERLY-2）或在 HER2 阴性肿瘤中联合 FEC 序贯新辅助化疗 4 周期和多西他赛 4 周期（BEVERLY-1）。使用 CellSearch 系统分别检测 7.5 和 4ml 血液中的 CTC 和 CEC。
2008 年 10 月至 2010 年 9 月，共纳入 152 例患者，其中 137 例患者可评估 CTC 和 CEC。基线时，55 例患者可检测到 CTC（39%）。化疗 4 周期后，CTC 急剧下降至 9%（P<0.01）。病理完全缓解（pCR）率为 40%。未发现 CTC 或 CEC 水平与 pCR 率之间存在相关性。中位随访时间为 43 个月。基线时 CTC 检测（≥1 CTC/7.5ml）与较短的 3 年无病生存（无 CTC 患者为 39%，而有 CTC 患者为 70%，P<0.01，HR 2.80）和较短的 3 年总生存（OS）相关（P<0.01）。多变量分析显示，较短的生存时间的独立预后参数是缺乏激素受体、无 pCR 和基线时 CTC 检测。基线时或治疗期间 CEC 水平无预后价值。
在这项非转移性 IBC 的两项前瞻性试验的汇总分析中，CTC 的检出率为 39%，对生存具有很强的独立预后价值。新辅助治疗后 pCR 联合基线时无 CTC 检测可分离出 IBC 患者的亚组，具有极好的 OS（94%的 3 年 OS），提示 CTC 计数可能成为 IBC 前瞻性试验分层的一部分。
