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Breast Cancer Research and Treatment

, Volume 145, Issue 3, pp 707–714 | Cite as

Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing

  • Priyanka SharmaEmail author
  • Jennifer R. Klemp
  • Bruce F. Kimler
  • Jonathan D. Mahnken
  • Larry J. Geier
  • Qamar J. Khan
  • Manana Elia
  • Carol S. Connor
  • Marilee K. McGinness
  • Joshua M. W. Mammen
  • Jamie L. Wagner
  • Claire Ward
  • Lori Ranallo
  • Catherine J. Knight
  • Shane R. Stecklein
  • Roy A. Jensen
  • Carol J. Fabian
  • Andrew K. Godwin
Clinical trial

Abstract

NCCN guidelines recommend genetic testing for all triple-negative breast cancer (TNBC) patients aged ≤60 years. However, due to the lack of prospective information in unselected patients, these guidelines are not uniformly adopted by clinicians and insurance carriers. The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population. Stage I–IV TNBC patients were enrolled on a prospective registry at academic and community practices. All patients underwent BRCA1/2 testing. Significant family history (SFH) was defined >1 relative with breast cancer at age ≤50 or ≥1 relative with ovarian cancer. Mutation prevalence in the entire cohort and subgroups was calculated. 207 TNBC patients were enrolled between 2011 and 2013. Racial/ethnic distribution: Caucasian (80 %), African–American (14 %), Ashkenazi (1 %). Deleterious BRCA1/2 mutations were identified in 15.4 % (32/207) of patients (BRCA1:11.1 %, BRCA2:4.3 %). SFH reported by 36 % of patients. Mutation prevalence in patients with and without SFH was 31.6 and 6.1 %, respectively. When assessed by age at TNBC diagnosis, the mutation prevalences were 27.6 % (≤50 years), 11.4 % (51–60 years), and 4.9 % (≥61 years). Using SFH or age ≤50 as criteria, 25 and 34 % of mutations, respectively, were missed. Mutation prevalence in patients meeting NCCN guidelines was 18.3 % (32/175) and 0 % (0/32) in patients who did not meet guidelines (p = .0059). In this unselected academic and community population with negligible Ashkenazi representation, we observed an overall BRCA mutation prevalence rate of 15.4 %. BRCA testing based on NCCN guidelines identified all carriers supporting its routine application in clinical practice for TNBC.

Keywords

Triple-negative breast cancer Germline BRCA mutation Genetic testing guidelines NCCN guidelines 

Abbreviations

NCCN

National Comprehensive Cancer Network

HBOC

Hereditary breast and/or ovarian cancer

TNBC

Triple-negative breast cancer

ER

Estrogen receptor

PR

Progesterone receptor

SFH

Significant family history

PARP

Poly(adenosine diposphate-ribose) polymerase

NICE

National Institute for Health and Care Excellence

ASCO/CAP

American Society of Clinical Oncologists and College of American Pathologists

Notes

Acknowledgments

This work was supported by The University of Kansas Department of Internal Medicine Research Career Award, KU Cancer Center’s CCSG [P30 CA168524] Biospecimen Repository; and Myriad Genetic Laboratories, Inc.

Conflict of interest

Priyanka Sharma currently conducts research sponsored by Myriad Genetic Laboratories, Inc. Jennifer Klemp and Larry Geier are members of the speakers’ bureau and receive honoraria from Myriad Genetic Laboratories, Inc. All remaining authors have declared no conflicts of interest.

Ethics Statement

All patients signed a written informed consent on a registry protocol approved by the University of Kansas Medical Center Human Subjects Committee, the designated Institutional Review Board, as required by 45 CFR 46 and 21 CFR 56.

Supplementary material

10549_2014_2980_MOESM1_ESM.tif (5.4 mb)
Supplementary material 1 (TIFF 5518 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Priyanka Sharma
    • 1
    Email author
  • Jennifer R. Klemp
    • 1
  • Bruce F. Kimler
    • 2
  • Jonathan D. Mahnken
    • 3
    • 4
  • Larry J. Geier
    • 1
  • Qamar J. Khan
    • 1
  • Manana Elia
    • 1
  • Carol S. Connor
    • 5
  • Marilee K. McGinness
    • 5
  • Joshua M. W. Mammen
    • 5
  • Jamie L. Wagner
    • 5
  • Claire Ward
    • 1
  • Lori Ranallo
    • 4
  • Catherine J. Knight
    • 4
  • Shane R. Stecklein
    • 6
  • Roy A. Jensen
    • 4
    • 6
  • Carol J. Fabian
    • 1
  • Andrew K. Godwin
    • 4
    • 6
  1. 1.Division of Hematology/Oncology, Department of Internal MedicineUniversity of Kansas Medical CenterWestwoodUSA
  2. 2.Department of Radiation OncologyUniversity of Kansas Medical CenterKansas CityUSA
  3. 3.Department of BiostatisticsUniversity of Kansas Medical CenterKansas CityUSA
  4. 4.The University of Kansas Cancer CenterKansas CityUSA
  5. 5.Department of SurgeryUniversity of Kansas Medical CenterKansas CityUSA
  6. 6.Department of Pathology & Laboratory MedicineUniversity of Kansas Medical CenterKansas CityUSA

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