Circulating tumor cells in breast cancer

Abstract

Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of-evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC.

Keywords: Breast cancer; Circulating tumor cells; Metastatic process; Prognostic markers.

Figure 1

Thresholds with clinical validity may have limited clinical utility. A: Progression‐Free Survival (PFS) curves of metastatic BC patients with ≥5 CTC/7.5 ml at baseline, according the CTC count at weeks 3–5: the red curve displays the PFS of patients who retains a CTC count ≥5 CTC/7.5 ml after 3–5 weeks on treatment and the blue curve displays the PFS of patients in whom the CTC count decreases <5 CTC/7.5 ml after 3–5 weeks on treatment (curves inspired from the European pooled analysis (Bidard et al., 2014)). B: Statistically significant log‐rank test between the two PFS curves, confirming the clinical validity of the ≥5 CTC/7.5 ml threshold. C: Using ≥5 CTC/7.5 ml after 3–5 weeks on treatment as a predictive test of early (<6 months) tumor progression, only 60% of patients with a positive test (i.e. ≥5 CTC/7.5 ml) have a PFS shorter than 6 months, while 75% of patients with <5 CTC/7.5 ml after 3–5 weeks on treatment have a PFS >6 months. The positive and negative predictive values of the 5 CTC/7.5 ml threshold are therefore limited when used as a test to predict early tumor progression.