Association of Circulating Tumor Cells, Megakaryocytes and a High Immune-Inflammatory Environment in Metastatic Breast Cancer

SIMPLE SUMMARY: In the present work on metastatic breast cancer patients, we studied liquid biopsy samples to analyze different biomarkers, such as circulating tumor cells, leukocytes, and platelets. We observed a correlation between a higher number of circulating tumor cells and a greater probability of detecting clusters and megakaryocytes among the patients. This observation was independent of the breast cancer subtype. We also confirmed the presence of megakaryocytes in the peripheral blood of cancer patients, which is an unusual finding. In addition, a higher pan-inflammatory value, calculated by dividing the product of neutrophils, monocytes, and platelets by the number of lymphocytes, was associated with lower overall survival, providing insight into the depth of the metastatic process. ABSTRACT: Liquid biopsy is becoming an important source of new biomarkers during the treatment of metastatic cancer patients. Using size-based microfluid technology, we isolated circulating tumor cells (CTCs) from metastatic breast cancer patients to evaluate their presence and cluster formation, as well as the presence of megakaryocytes and immune-inflammatory blood cells, and to correlate their presence with clinicopathological data and overall survival (OS). In total, 59 patients (median age 60.4 years) were included in the study: 62.7% luminal A/B-like, 20.3% HER2-positive, and 17% triple-negative. Our results showed that at least one CTC was present in 79.7% and ≥5 CTCs in 35.2% of the patients. CTC clusters were present in patients with ≥5 CTCs only (in 19.2% of them), and megakaryocytes were present in 52% of all patients. The presence of CTC clusters and megakaryocytes was positively associated with the CTC count. Patients with low pan-inflammatory value (PIV), low systemic immune-inflammatory index (SII), and low relative change from baseline (ΔPIV%, ΔSII%) were associated with significantly higher OS than their counterparts. ΔPIV%, the presence of infection in the last month, and a long duration of metastatic disease were identified as independent prognostic factors for OS. The interplay of CTCs, CTC clusters, megakaryocytes, and PIV needs to be further explored.