Skip to main content
SSO 2024 Annual Meeting Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Presentation Icons
Recorded for On-Demand Viewing
Recorded for On-Demand Viewing
Back

Breast

E4: Circulating tumor cell mechanical conditioning (MeCo) score- a predictor of metastatic risk in early-stage breast cancer

Introduction: The mechanical conditioning (MeCo) score is a gene expression signature acquired by cancer cells in primary breast tumors and is reflective of responsiveness to matrix stiffness. Chromatin remodeling in response to stiffness allows cancer cells to remain aggressive without mechanical stimulation by the primary tumor (PT). Patients with high MeCo scores are at higher risk of developing metastatic breast cancer compared to those with low scores (Watson et al 2021, PMID: 34192535). Circulating tumor cells (CTCs) are associated with a higher rate of metastatic dissemination and adverse survival outcomes, making CTC detection in breast cancer patients a notable prognostic biomarker for metastasis. The goal of our study was to determine whether CTCs retain high MeCo scores and if these scores are maintained during late-stage breast cancer in metastatic sites.

Methods: CTCs were isolated from two patient cohorts: stage II-III breast cancer patients (Lang et al 2018, PMID: 29868978) and metastatic breast cancer patients (Ring et al 2022, PMID: 35000083). Gene expression profiling using RNA Seq was performed in CTCs, matching PT and metastases (MET). A quantile normalization approach was used to compare cohorts. MeCo scores were computed for all samples. Wilcoxon matched-pairs signed rank test was performed for comparison of MeCo scores from matching samples within each cohort; Mann-Whitney unpaired test was used to compare MeCo scores of CTCs across cohorts.

Results: In 12 early-stage breast cancer patients, MeCo scores of CTCs were significantly higher than their matched PTs (p=0.026). In 26 metastatic patients, MeCo scores of METs were significantly higher than matching CTCs (p=0.0004). MeCo scores of CTCs were similar between early- and late-stage breast cancer. Ninety-eight percent of genes in the MeCo score were present in the evaluable CTC, MET and PT samples.

Conclusions: The MeCo score is higher in CTCs compared to PTs and is higher in METs compared to CTCs in early- and late-stage breast cancer, respectively. These findings show that mechanical conditioning is retained during metastatic progression and rises through the metastatic cascade. The results support that breast cancer cells with high MeCo scores are more competent with–and potentially selected for by–metastatic progression. The findings provide a novel feature of CTCs, the MeCo score, which is associated with higher capacity for metastasis. CTC MeCo score could provide a prognostic tool to predict metastatic risk in early-stage breast cancer patients.

Learning Objectives:

  • Describe the role of circulating tumor cells in breast cancer patients.
  • Define mechanical conditioning (MeCo) score.
  • Describe the progression of MeCo score in the metastatic cascade of patients with breast cancer.