Real-World Eligibility for Germline Multigene Panel Testing in Breast Cancer: An Evaluation of Current Testing
Roxana Pintican1,2,3, Nicoleta Antone Zenovia1,2,4, Vlad Alexandru Gata1,2,5
1Department of Radiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Diagnostics (Basel, Switzerland)
|July 28, 2026
Summary
Germline multigene testing in breast cancer care is crucial. Current guidelines like NCCN and ESMO have varying effectiveness in identifying pathogenic variants, suggesting broader testing access before surgery is beneficial.
Area of Science:
- Oncology
- Genetics
- Breast Cancer Research
Background:
- Germline multigene testing is becoming standard in breast cancer management.
- Uncertainty exists regarding the effectiveness of current eligibility frameworks in identifying pathogenic variant carriers in real-world patient populations.
Purpose of the Study:
- To evaluate the performance of existing eligibility criteria (NCCN, ESMO, ASBrS) in identifying pathogenic germline variants in breast cancer patients.
- To assess the implications for clinical practice and surgical decision-making.
Main Methods:
- Retrospective observational study of 556 breast cancer patients undergoing germline multigene testing.
- Retrospective assessment of testing eligibility using NCCN, ESMO, and ASBrS criteria.
- Analysis of family history and surgical data.
Main Results:
- Pathogenic variants were found in 24.6% of patients; variants of uncertain significance in 55.8%.
- NCCN criteria identified 98.5% of pathogenic variant carriers but lacked specificity.
- ESMO criteria were more selective (68.6% of carriers) and significantly associated with pathogenic variant status (OR=3.08).
- 42.3% of carriers had no family history of malignancy; only 16.8% underwent prophylactic surgery.
Conclusions:
- NCCN criteria are highly sensitive but not specific for identifying pathogenic variants.
- ESMO criteria offer better selectivity.
- Findings support expanding germline testing access prior to surgical intervention for breast cancer patients.
