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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

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgments

We would like to thank Cancer Research Collaboration for support for this project. In addition, we thank Shuwei Li, PhD, Holly LaDuca, MS, CGC, and the staff at Breastlink Medical Group Inc. for technical assistance.

Disclosure

NSK and LDC have been consultants for Ambry Genetics. AKB has been a consultant for Myriad Genetics. KCB was and REM is employed by Ambry Genetics. The other authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Surgical Oncology, Breastlink, Orange, CA, USA

    Nimmi S. Kapoor MD, Carlee A. Blakemore BS & John G. West MD, FACS

  2. Department of Surgical Oncology, Breastlink, Laguna Hills, CA, USA

    Nimmi S. Kapoor MD & Lisa D. Curcio MD, FACS

  3. Department of Surgical Oncology, Breastlink, Temecula, CA, USA

    Amy K. Bremner MD

  4. Ambry Genetics, Aliso Viejo, CA, USA

    Rachel E. McFarland BS & Kimberly C. Banks MS, CGC, MBA

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  1. Nimmi S. Kapoor MD
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  2. Lisa D. Curcio MD, FACS
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  3. Carlee A. Blakemore BS
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Correspondence to Nimmi S. Kapoor MD.

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Kapoor, N.S., Curcio, L.D., Blakemore, C.A. et al. 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. Ann Surg Oncol 22, 3282–3288 (2015). https://doi.org/10.1245/s10434-015-4754-2

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