Liquid Biopsy Profiling with Multiple Tests in Patients with Metastatic Breast Cancer

Area of Science:

• Oncology
• Genomics
• Translational Research

Background:

• Liquid biopsy tests are crucial for cancer management.
• The Blood Profiling Atlas in Cancer (BloodPAC) consortium fosters collaborative research.
• Standardization of liquid biopsy platforms is needed for clinical implementation.

Purpose of the Study:

• To demonstrate a multisite liquid biopsy testing framework.
• To analyze cell-free DNA (cfDNA) mutations in metastatic breast cancer patients.
• To assess the concordance of different sequencing platforms in a real-world setting.

Main Methods:

• Longitudinal blood specimens from 38 metastatic breast cancer patients were used.
• Three laboratories utilized different targeted sequencing platforms to analyze cfDNA.
• Whole-genome copy number profiling of cfDNA and circulating tumor cells (CTCs) was performed.

Main Results:

• Mutational profiles revealed common breast cancer alterations, with actionable mutations found in 40% of hormone-receptor-positive patients.
• Perfect inter-assay concordance was observed for mutations in 12 shared genes above the limit of detection.
• cfDNA tumor fractions and CTC abundance showed significant inter-patient heterogeneity and complementary information.

Conclusions:

• The described multisite framework is a viable resource for future liquid biopsy biomarker trials.
• Multimodal liquid biopsy approaches combining cfDNA and CTCs can provide complementary insights.
• This framework supports the development of liquid biopsy tests to guide clinical care in breast cancer.