Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment

Abstract

IntroductionCirculating tumor cells (CTCs) represent an independent predictor of outcome in patients with metastatic breast cancer (MBC). We assessed the prognostic impact of CTCs according to different first-line systemic treatments, and explored their potential predictive value in MBC patients.MethodsWe retrospectively evaluated 235 newly diagnosed MBC patients, treated at the University of Texas MD Anderson Cancer Center. All patients had a baseline CTC assessment performed with CellSearch®. Progression-free survival and overall survival were compared with the log-rank test between groups, according to CTC count (< 5 vs. ≥ 5) and type of systemic therapy. We further explored the predictive value of baseline CTCs in patients receiving different treatments.ResultsAt a median follow-up of 18 months, the CTC count was confirmed to be a robust prognostic marker in the overall population (median progression-free survival 12.0 and 7.0 months for patients with CTC < 5 and ≥ 5, respectively; P < 0.001). Conversely, in patients with human epidermal growth factor receptor-2-overexpressed/amplified tumors receiving trastuzumab or lapatinib, the baseline CTC count was not prognostic (median progression-free survival 14.5 months for patients with CTC < 5 and 16.1 months for those with CTC ≥ 5; P = 0.947). Furthermore, in patients with human epidermal growth factor receptor-2 normal tumors, a baseline CTC count ≥ 5 identified subjects who derived benefit from more aggressive treatments, including combination chemotherapy and chemotherapy plus bevacizumab.ConclusionsThis analysis suggests that the prognostic information provided by CTC count may be useful in patient stratifications and therapeutic selection, particularly in the group with positive CTCs, in which various therapeutic choices may procure differential palliative benefit.

PIK3CA Mutational Status in Circulating Tumor Cells Can Change During Disease Recurrence or Progression in Patients with Breast Cancer

“…In metastatic breast cancer (MBC), CTCs represent an independent prognostic factor for progression-free survival (PFS) and OS, and the CTC enumeration assay (CellSearch, Veridex) was cleared by FDA for metastatic breast, prostate, and colorectal cancer and many groups have verified these findings (11)(12)(13). Increased numbers of CTC before the second cycle of therapy was an early predictive marker of poor PFS and OS, and could be used to monitor treatment benefit, whereas CTC decrease under treatment was stronger with targeted therapy (14).…”

Changes in Keratin Expression during Metastatic Progression of Breast Cancer: Impact on the Detection of Circulating Tumor Cells

“…Alternatively to bone marrow samples, which are difficult to obtain in a routine fashion, blood has been shown to be a valuable source for the identification of dissociated tumor cells (6)(7)(8). Detection of these circulating tumor cells (CTC) might be used to monitor and predict therapy response in cancer treatment because repeated samples can be taken easily (9)(10)(11).…”

Prognostic Significance of Circulating Tumor Cells and Serum CA15-3 Levels in Metastatic Breast Cancer, Single Center Experience, Preliminary Results

“…A correlation was found between the basaline CTC count and survival times. In multivariate analysis the basaline CTC count was confirmed as an independent predictor of PFS and OS (Giuliano et al, 2011). On the other hand, Takudome et al evaluated the basaline CTC count in heavily treated metastatic BC patients.…”