Sustained prognostic impact of circulating tumor cell status and kinetics upon further progression of metastatic breast cancer.

Abstract

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 (CTCBL) and within 4weeks of tumor progression (CTCPD) 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 7.5ml 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 KineticsBL-PD. Median follow-up was 29.9 [21.2, 40.0] months. CTCPD positivity (37%, n = 38) was associated with a significantly shorter OS than CTCPD negativity (8.0 [5.1, 10.9] vs 22.6 [15.3, 39.8] months; P < 0.001). Alternating KineticsBL-PD 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 CTCPD status to clinicopathological characteristics and CTCBL 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.