Division of Gynecologic Oncology, National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Department of Obstetrics and Gynecology, University Hospital Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
Breast Cancer Res Treat. 2019 Jan;173(1):155-165. doi: 10.1007/s10549-018-4972-y. Epub 2018 Oct 1.
Serial longitudinal enumeration of circulating tumor cells (CTCs) has shown its prognostic value on progression-free survival and overall survival (OS) in patients with stage IV breast cancer. This study prospectively evaluated the role of CTCs as a prognostic marker during further progression of metastatic breast cancer (MBC).
Among 476 MBC patients recruited between 2010 and 2015, the 103 patients with a known CTC status at baseline (CTC) and within 4 weeks of tumor progression (CTC) were included. Progressive disease (PD) was defined according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Using the CellSearch method, < 5 and ≥ 5 CTCs per 7.5 ml blood were determined as negative and positive, respectively. A shift in CTC status from baseline to progression ([Formula: see text] to [Formula: see text] and vice versa) was considered as alternating Kinetics.
Median follow-up was 29.9 [21.2, 40.0] months. CTC positivity (37%, n = 38) was associated with a significantly shorter OS than CTC negativity (8.0 [5.1, 10.9] vs 22.6 [15.3, 39.8] months; P < 0.001). Alternating Kinetics was observed in 24% of the patients. This significantly changed the OS prediction of [Formula: see text] patients ([Formula: see text] vs [Formula: see text], 11.4 [9.7, not available (NA)] vs. 7.6 [4.4, 11.5] months; P = 0.044) and [Formula: see text] patients ([Formula: see text] vs. [Formula: see text], 8.4 [4.0, NA] vs. 22.6 [18.9, NA] months, respectively; P < 0.001). Prediction of survival was significantly improved (P = 0.002) by adding CTC status to clinicopathological characteristics and CTC status.
CTC status upon further disease progression is a prognostic factor that could significantly improve well-established models. Thus, it represents a potential additional instrument supporting treatment decision.
循环肿瘤细胞（CTC）的连续纵向计数已显示其在 IV 期乳腺癌患者无进展生存期和总生存期（OS）方面的预后价值。本研究前瞻性评估了 CTC 作为转移性乳腺癌（MBC）进一步进展时的预后标志物的作用。
在 2010 年至 2015 年间招募的 476 例 MBC 患者中，纳入了基线（CTC）和肿瘤进展后 4 周内（CTC）已知 CTC 状态的 103 例患者。根据实体瘤反应评估标准（RECIST，版本 1.1）定义疾病进展（PD）。使用 CellSearch 方法，<5 个和≥5 个 CTC 个/7.5ml 血液分别确定为阴性和阳性。从基线到进展的 CTC 状态的转变（[Formula: see text]到[Formula: see text]，反之亦然）被认为是交替动力学。
中位随访时间为 29.9 [21.2，40.0]个月。与 CTC 阴性（8.0 [5.1，10.9] vs 22.6 [15.3，39.8]个月；P<0.001）相比，CTC 阳性（37%，n=38）与 OS 显著缩短相关。在 24%的患者中观察到交替动力学。这显著改变了[Formula: see text]患者的 OS 预测（[Formula: see text] vs [Formula: see text]，11.4 [9.7，无（NA）] vs. 7.6 [4.4，11.5]个月；P=0.044）和[Formula: see text]患者（[Formula: see text] vs. [Formula: see text]，8.4 [4.0，NA] vs. 22.6 [18.9，NA]个月，分别；P<0.001）。通过将 CTC 状态添加到临床病理特征和 CTC 状态中，生存预测得到显著改善（P=0.002）。
进一步疾病进展时的 CTC 状态是一个预后因素，可以显著改善成熟的模型。因此，它代表了支持治疗决策的潜在附加工具。
