Abstract 3208: Impact of targeted therapy on circulating tumor cells in metastatic breast cancer treated by first-line chemotherapy: IC 2006-04 study

Abstract

Abstract Circulating tumor cells (CTC) have been reported to be a prognostic marker in metastatic breast cancer. This study was designed to test whether changes in CTC counts during treatment are associated with outcome of first-line chemotherapy with/without targeted therapy. Methods: CTC were counted (CellSearch®) at baseline, before cycle 2 (C2) and C3/4 in 267 metastatic breast cancer patients. Usual prognostic variables, serum tumor markers, tumor response according to RECIST criteria and events were prospectively registered and compared with CTC status and outcome over time. Results: Median follow-up was 16 months, 45 patients (17%) had HER2 positive tumor and received trastuzumab, 55 (21%) had triple negative tumor, 125 received bevacizumab associated with CT. Baseline CTC positivity (65%; ≥1CTC/7.5ml threshold, 45% ≥5CTC/7.5ml threshold) was correlated with tumour markers, bone/liver involvement and number of metastatic sites, as well as performance status but was not statistically different according to breast cancer subtypes (hormone-positive, HER2-positive or triple-negative). At multivariate analysis, CTC ≥5CTC/7.5ml was an independent prognostic factor for progression-free survival (PFS), RR=1.9 (CI95% 1.26-2.88), p=0.002, with triple negative status, poor performance status and elevated CEA. For overall survival, CTC ≥5CTC/7.5ml was an independent prognostic factor with triple negative status and poor performance status (RR=2.41, p=0.02). Changes with a threshold ≥5CTC/7.5ml, between baseline and Cycle 2 were highly correlated with both PFS (p=5e-07) and OS (p=3e-07). Persistent CTC positivity at C2 was associated with lower tumor response (p=4e-03). Among CTC-positive patients at baseline treated by chemotherapy only, chemotherapy/bevacizumab and chemotherapy/anti-HER2, CTC counts decreased respectively below the ≥5CTC/7.5ml positivity threshold before cycle 2 in 53%, 64% and 83% of patients, and before cycle 3 or 4, in 62%, 77% and 100% of patients (p=0.04). Prognostic value of CTC count at baseline and C2 remained in all subgroups. Conclusions: CTC count appeared to decrease more markedly in the patients who received also bevacizumab or trastuzumab. However, CTC remain a reliable independent prognostic marker in metastatic breast cancer treated by first-line chemotherapy with/without targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3208. doi:10.1158/1538-7445.AM2011-3208