173P - Unveiling a novel EpCAM-CD24+ circulating cells with unidentified origin associated with breast cancer distant metastasis

Background

Breast cancer (BC) presents challenges in predicting disease progression despite advancements in treatment and monitoring. Circulating tumor cells (CTCs) were initially seen as promising for prognosis via liquid biopsy, but complexities in their investigation have emerged over the past 15 years. Variability in isolation methods and the absence of universal CTC markers hinder standardization and comparison of research findings. In the present study we focused on CD24 which shows potential as a prognostic marker of BC. This study aims to elucidate the prognostic significance of CD24+ circulating cells in peripheral blood of BC patients.

Methods

The study included 57 patients with invasive breast carcinoma of no special type (IC NST) T1-4N0-3M0-1. Circulating cell phenotypes assessment was carried out by flow cytometry (Novocyte 3000, ACEA Biosciences, USA) using monoclonal antibody cocktail.

Results

In our investigation we utilized epithelial markers EpCAM and cytokeratin 7/8 to assess CTCs, including both metastatic and non-metastatic BC patients. Surprisingly, these markers were insufficient in identifying CTC populations indicative of distant metastasis in BC. However, we made the intriguing discovery of CD45-CD24+ circulating cells lacking epithelial markers EpCAM and CK7/8 associated with distant metastasis. Increased level of CD45-EpCAM-CK7/8-CD24+N-cadherin- circulating cells were observed among patients with established metastases and those who developed metastatic lesions during subsequent monitoring. Furthermore, exceeding a threshold of 218.3 cells per milliliter of peripheral blood before treatment predicted a 12-fold increase in metastatic risk and a 3-fold reduction in DMFS over a 90-month period. The unveiled cell population could originate with equal probability from epithelial cells that have undergone EMT or from immature cells from bone marrow. However, it should be noted that these CCs do not align with any recognized stages of monocyte or neutrophil maturation.

Conclusions

The count of CD45-EpCAM-CK7/8-CD24+N-cadherin- CCs was associated with distant metastasis, as their numbers were elevated in peripheral blood of patients with metastases during the follow-up period.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The study was supported by the Russian Science Foundation (grant #23-15-00135).

Disclosure

All authors have declared no conflicts of interest.