18P - Molecular characterization of circulating tumor cells in metastatic breast cancer using shallow whole genome sequencing

Background

Metastatic breast cancer is the leading cause of cancer-related mortality in women, largely due to challenges in early detection of metastasis and limitations of current treatment options. Circulating Tumor Cells (CTC) are critical to metastatic dissemination, making their detection and characterization through liquid biopsy a promising advancement in oncology. While counting CTC can offer insights into prognosis, molecular characterization has the potential to refine therapeutic strategies and enable early detection of treatment resistance. This study focuses on the molecular analysis of CTC using a shallow Whole Genome Sequencing (sWGS) approach to enhance the understanding of CTC in metastatic breast cancer.

Methods

114 CTC were isolated from 10 patients with metastatic luminal breast cancer using DEPArray technology. After sorting, single cells underwent Whole Genome Amplification (WGA) followed by shallow sWGS to identify common copy number alteration (CNA) patterns. Sequencing was performed on the Illumina MiSeq platform. CNA were called using a home-made pipeline. The prognostic value of CNA signatures was evaluated using data from The Cancer Genome Atlas (TCGA) dataset (n=466), with Kaplan-Meier curves generated using the log-rank test.

Results

Six molecular CNA signatures were identified in patients. Notably, four of these signatures were strongly associated with worse prognosis: deletions of chromosome 1, amplifications of chromosome 1, hemizygous deletions of X chromosome, deletions of chromosome 4 and 13. The prognostic significance was confirmed in primary breast carcinomas from the TCGA consortium. The identification of molecular signatures on CTC provides valuable insights into the genetic landscape of breast cancer. The association of specific aberrations with poorer outcomes underscores the potential of these markers for guiding risk assessment and therapeutic strategies. The validation in primary breast carcinomas further supports the clinical relevance of integrating molecular signatures into personalized treatment and patient management.

Conclusions

Our study demonstrated the utility of molecular signatures in CTC from breast cancer patients in aiding better prognosis.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Institute of Surgical Pathology, ASU FC Udine.

Funding

Fondazione AIRC, project title: “Dissecting the heterogeneity of circulating tumor cells in metastatic breast cancer to predict clinical outcome” (PI Daniela Cesselli).

Disclosure

All authors have declared no conflicts of interest.