Multigene Panel Testing Detects Equal Rates of Pathogenic BRCA1/2 Mutations and has a Higher Diagnostic Yield Compared to Limited BRCA1/2 Analysis Alone in Patients at Risk for Hereditary Breast Cancer.

Autor: Kapoor NS; Department of Surgical Oncology, Breastlink, Orange, CA, USA, nimsikapoor@gmail.com., Curcio LD, Blakemore CA, Bremner AK, McFarland RE, West JG, Banks KC
Jazyk: angličtina
Zdroj: Annals of surgical oncology [Ann Surg Oncol] 2015 Oct; Vol. 22 (10), pp. 3282-8. Date of Electronic Publication: 2015 Jul 29.
DOI: 10.1245/s10434-015-4754-2
Abstrakt: Background: Recently introduced multigene panel testing including BRCA1 and BRCA2 genes for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study was to evaluate rates of pathogenic BRCA1/2 mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multigene testing.
Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2 testing only (limited group, n = 629) to those who underwent multigene testing with 5-43 cancer-related genes (panel group, n = 337).
Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0 vs. 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5 vs. 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9 % (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified.
Conclusions: Multigene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly as a result of non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from up-front, more efficient, multigene panel testing.
Databáze: MEDLINE
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