Circulating tumor cells et al.: towards a comprehensive liquid biopsy approach in breast cancer.

Liquid biopsy has emerged as a crucial tool in managing breast cancer (BC) patients, offering a minimally invasive approach to detect circulating tumor biomarkers. Until recently, the majority of the studies in BC focused on evaluating a single liquid biopsy analyte, primarily circulating tumor DNA and circulating tumor cells (CTCs). Despite the proven prognostic and predictive value of CTCs, their low abundance when detected using enrichment methods, especially in the early stages, poses a significant challenge. It is becoming evident that combining diverse circulating biomarkers, each representing different facets of tumor biology, has the potential to enhance the management of patients with BC. This article emphasizes the importance of considering these biomarkers as complementary/synergistic rather than competitive, recognizing their ability to contribute to a comprehensive disease profile. The review provides an overview of the clinical significance of simultaneously analyzing CTCs and other biomarkers, including cell-free circulating DNA, extracellular vesicles, non-canonical CTCs, cell-free RNAs, and non-malignant cells. Such a comprehensive liquid biopsy approach holds promise not only in BC but also in other cancer types, offering opportunities for early detection, prognostication, and therapy monitoring. However, addressing associated challenges, such as refining detection methods and establishing standardized protocols, is crucial for realizing the full potential of liquid biopsy in transforming our understanding and approach to BC. As the field evolves, collaborative efforts will be instrumental in unlocking the revolutionary impact of liquid biopsy in BC research and management.

Latest advances in clinical studies of circulating tumor cells in early and metastatic breast cancer.

Circulating tumor cells (CTCs) have emerged as a promising biomarker in breast cancer, offering insights into disease progression and treatment response. While CTCs have demonstrated prognostic relevance in early breast cancer, more validation is required to establish optimal cut-off points. In metastatic breast cancer, the detection of CTCs using the Food and Drug Administration-approved CellSearch® system is a strong independent prognostic factor. However, mesenchymal CTCs and the Parsortix® PC1 system show promise as alternative detection methods. This chapter offers a comprehensive review of clinical studies on CTCs in breast cancer, emphasizing their prognostic and predictive value in different stages of the disease and provides insights into potential future directions in CTC research.

Racial disparities in neutrophil counts among patients with metastatic breast cancer during treatment with CDK4/6 inhibitors.

PURPOSE: The three CDK4/6 inhibitors (CDK4/6i) approved for use in HR-positive/HER2-negative metastatic breast cancer (MBC), palbociclib, ribociclib, and abemaciclib, are generally well tolerated; however, neutropenia is a common toxicity. Within the general population, neutropenia has been shown to be more common in individuals of African descent. The landmark CDK4/6i trials in MBC lacked racial diversity in their patient populations. We aimed to assess the toxicity profiles of CDK4/6is in a racially diverse population. METHODS: We conducted a retrospective study at Montefiore Medical Center in patients with HR-positive/HER2-negative MBC prescribed CDK4/6i as first or subsequent line therapy between January 2015 and April 2020. Baseline characteristics and laboratory data at various treatment timepoints were collected. RESULTS: The final analysis included 182 patients, of whom 46% were Black. Baseline absolute neutrophil count (ANC) was lower in the Black vs. Non-Black cohort (p = 0.001) but the change in ANC from baseline (delta-ANC) was smaller in the Black cohort, and the ANC at different treatment timepoints was similar between groups. There was no difference in the rate of infection or number of dose delays/reductions between racial groups. We did not find any difference in PFS between Black and Non-Black groups, regardless of the presence of CDK4/6i-induced neutropenia. CONCLUSION: We analyzed toxicity profiles of 182 patients with HR-positive/HER2-negative MBC treated with CDK4/6i. Despite the lower baseline ANC seen in our Black cohort, treatment toxicities were similar between racial groups. Long-term outcomes with CDK4/6i therapy, measured by PFS, were similar between Black vs. Non-Black patients.