Identifying germline pathogenic variants in breast cancer using tumor sequencing.

Area of Science:

• Oncology
• Genetics
• Molecular Diagnostics

Background:

• Germline pathogenic variants (gPV) significantly increase breast cancer risk.
• Accurate identification of gPV carriers is crucial for personalized treatment and risk management.
• Tumor sequencing offers a potential alternative or complementary method for detecting gPV.

Purpose of the Study:

• To evaluate the performance of an in-house tumor sequencing panel for identifying breast cancer patients with gPV.
• To assess the sensitivity, specificity, and reliability of the panel for clinical implementation.

Main Methods:

• Retrospective analysis of 90 breast cancer patients with prior germline genetic testing.
• Blinded tumor sequencing using an in-house panel (VHIO-300).
• Calculation of sensitivity, specificity, PPV, NPV, and Cohen's kappa coefficient.

Main Results:

• The panel identified 91% of gPVs, with 7% false positives.
• Sensitivity was 91%, specificity 93%.
• Cohen's kappa coefficient was 0.84, indicating reliable agreement with germline testing.

Conclusions:

• The in-house tumor sequencing panel demonstrates acceptable performance for identifying breast cancer patients with gPV.
• The panel's reliability supports its potential for clinical use in gPV detection.