Integrating ctDNA Dynamics and Sequential Organoid Drug Screening Enhances Breast Cancer Treatment Efficacy

Area of Science:

• Oncology
• Genomics
• Personalized Medicine

Background:

• Dynamic changes in circulating tumor DNA (ctDNA) variant allele frequency can indicate real-time treatment effectiveness.
• Adjusting breast cancer therapies based on ctDNA dynamics may allow for precise regimen selection to combat evolving resistance.

Purpose of the Study:

• To develop and evaluate a therapeutic strategy that integrates ctDNA dynamics with sequential organoid drug screening for optimizing breast cancer treatment.
• To assess the correlation between ctDNA clearance and disease-free survival in breast cancer patients.

Main Methods:

• Developed a therapeutic approach combining ctDNA monitoring with sequential organoid drug screening.
• Performed targeted deep sequencing on plasma samples from 71 breast cancer patients.
• Analyzed 40 breast cancer organoid models for mutation profiling and drug sensitivity testing.

Main Results:

• ctDNA clearance was found to correlate with improved disease-free survival in breast cancer patients.
• Organoid culture supernatants proved effective for comprehensive mutation profiling.
• Organoid models demonstrated potential for drug sensitivity testing.

Conclusions:

• Combining ctDNA monitoring with organoid-based drug screening offers a promising approach to guide treatment strategy adjustments in breast cancer.
• This integrated method can help optimize patient outcomes by enabling personalized and dynamic therapeutic modifications to overcome resistance.