Mapping breast cancer therapy with circulating tumor cells: The expert perspective

Circulating tumor cells (CTCs) have emerged as a key prognostic biomarker for breast cancer, with their role becoming more pronounced in metastatic cases. In metastatic breast cancer, having five or more CTCs per 7.5 mL of blood is linked to poorer survival and more aggressive disease, marking it as stage IVaggressive. Conversely, fewer than five CTCs per 7.5 mL of blood indicates a less aggressive, stage IVindolent disease. Additionally, molecular CTCs characterization provides a real-time snapshot of tumor biology, capturing its temporal and spatial variability and providing insights into tumor behavior. Beyond their role in predicting outcomes, CTCs can help guide treatment intensity as shown in clinical trials like the STIC trial, offering a new way to tailor therapy alongside other liquid biopsy biomarkers such as circulating tumor DNA. The aim of our review is to focus on both enumeration and phenotyping of CTCs and examine how CTC-guided strategies can improve treatment tailoring and patient outcomes. We also explore the potential for integrating CTCs with other biomarkers, such as circulating tumor DNA, and discuss how innovative biomarker-driven clinical trial designs could further advance personalized treatment strategies.