TY - JOUR
T1 - Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry
T2 - Implications for hereditary breast and/or ovarian cancer syndrome testing
AU - Sharma, Priyanka
AU - Klemp, Jennifer R.
AU - Kimler, Bruce F.
AU - Mahnken, Jonathan D.
AU - Geier, Larry J.
AU - Khan, Qamar J.
AU - Elia, Manana
AU - Connor, Carol S.
AU - McGinness, Marilee K.
AU - Mammen, Joshua M.W.
AU - Wagner, Jamie L.
AU - Ward, Claire
AU - Ranallo, Lori
AU - Knight, Catherine J.
AU - Stecklein, Shane R.
AU - Jensen, Roy A.
AU - Fabian, Carol J.
AU - Godwin, Andrew K.
N1 - Funding Information:
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.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - Genetic testing guidelines
KW - Germline BRCA mutation
KW - NCCN guidelines
KW - Triple-negative breast cancer
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U2 - 10.1007/s10549-014-2980-0
DO - 10.1007/s10549-014-2980-0
M3 - Article
C2 - 24807107
AN - SCOPUS:84901617612
SN - 0167-6806
VL - 145
SP - 707
EP - 714
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -