Longitudinal analysis of circulating tumor cell numbers improves tracking metastatic breast cancer progression

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Hormone-responsive breast cancer is common, but distant metastases significantly reduce survival.
• Monitoring metastatic breast cancer (mBC) progression is crucial for patient management.
• Circulating tumor cells (CTCs) show diagnostic potential but lack established prognostic value.

Purpose of the Study:

• To evaluate the prognostic value of circulating tumor cell (CTC) numbers and their dynamics in advanced breast cancer.
• To assess molecular changes in CTCs compared to primary tumors, focusing on genes related to endocrine therapy resistance.
• To determine if CTC genetic analysis can track resistance and guide treatment decisions.

Main Methods:

• Longitudinal study of 135 metastatic breast cancer patients with three serial blood collections.
• Circulating tumor cells (CTCs) detected and isolated using the EpCAM-independent CytoTrack system.
• Next-generation sequencing (NGS) analysis of isolated CTCs for mutational profiling.

Main Results:

• CTC status is significant for progression-free and overall survival.
• Longitudinal monitoring of CTC dynamics provides advantages over single counts for predicting clinical progression.
• High genetic and phenotypic heterogeneity in CTCs suggests divergent metastatic lesions and potential early dissemination.

Conclusions:

• Continuous monitoring of CTCs and their dynamics is crucial for managing advanced breast cancer.
• Observed CTC heterogeneity highlights the complexity of metastatic disease.
• This study did not confirm a tendency for activating mutations in CTCs driving anti-estrogen resistance.