Abstract P2-01-03: Improved prognostic information by serial monitoring of CTC enumeration and CTC-clusters from baseline to six months in patients with metastatic breast cancer scheduled for 1st line systemic therapy
Authors: Larsson A-M , Jansson S , Bendahl P-O , Baker S , Graffman C , Lundgren C , Loman N , Aaltonen KE , Rydén L 
Published: February 2018

Background: Detection and enumeration of circulating tumor cells (CTCs) allows real time monitoring of disease evolvement. In women with metastatic breast cancer (MBC), a CTC count of ≥5 CTCs is associated with decreased progression-free survival (PFS) and overall survival (OS). Serial sampling after therapy initiation has indicated that longitudinal CTC enumeration adds prognostic information, but data from long time sampling is sparse. The aim of this study was to evaluate if prospective longitudinal detection of CTC count and CTC clusters in women with newly diagnosed MBC can improve prognostication and monitoring of patients in the clinical setting.

Methods: Longitudinal blood samples were collected at baseline (BL) and after 1, 3 and 6 months in 156 women with MBC scheduled for 1st line systemic therapy. CTC enumeration and cluster detection were performed by the CellSearch® system in a prospective monitoring trial (NCT01322893). 115 patients had evaluable samples at all time-points. Primary endpoint was PFS and secondary endpoint was OS at BL in relation to CTC count and as landmark analyses during treatment. In addition, change in CTC count during therapy was compared to progressive disease (PD) versus non-PD. Structured clinical and radiological evaluation for PD was performed every 3rd month.

Results: Seventy-nine (52%) of 152 evaluable patients had ≥5 CTC and 14/79 patients had CTC-clusters (33 clustered CTC) at BL. Median follow-up time was 25 (7-69) months. Patients with ≥5 CTCs had inferior PFS and OS in uni-(data not shown) and multivariable analysis (HRPFS 1.91 (1.26-2.91), P=0.003) (HROS 3.57 (2.02-6.31), P&lt;0.001) at BL. Presence of clusters at BL was prognostic for OS (HROS 2.37 (1.25-4.51), P=0.008). Longitudinal landmark analysis of number of CTCs and presence of CTC clusters showed a time-dependent increase in HR during treatment for CTCs and CTC-clusters and predicted worse PFS and OS at all time-points. Stratifying patients based on CTC count and presence of clusters revealed four risk groups (0, 1-4, ≥5 CTC, ≥5 CTC + clusters) where patients with clusters had inferior PFS and OS at all time points. Change in CTC count from BL to 1 and 3 months, and from 3 to 6 months was significantly related to evaluation at 3 and 6 months (PD vs non-PD, P=0.013 (3 months), P=0.016 (6 months)) and change in CTC count from BL to 1, 3 and 6 months was also significantly predictive of both PFS and OS. Notably, survival was significantly inferior for patients with persistent CTC ≥5 during treatment.

Discussion: CTC is an independent prognostic factor for MBC patients scheduled for 1st line systemic therapy. By longitudinal monitoring during treatment, the prognostic information by presence of ≥5 CTC and clusters increases over time and supports long time monitoring of patients. Importantly, detection of CTC-clusters identifies a subgroup of patients with dismal prognosis at all time-points indicating that CTC-clusters renders important clinical information. Change in CTC count during systemic therapy is related to outcome of evaluation and prognosis at all time-points.

Citation Format: Larsson A-M, Jansson S, Bendahl P-O, Baker S, Graffman C, Lundgren C, Loman N, Aaltonen KE, Rydén L. Improved prognostic information by serial monitoring of CTC enumeration and CTC-clusters from baseline to six months in patients with metastatic breast cancer scheduled for 1st line systemic therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-01-03.