Caiqian Cropper1, Ashley Woodson2, Banu Arun1,3, Carlos Barcenas3, Jennifer Litton1,3, Sarah Noblin1,4, Diane Liu5, Minjeong Park5, Molly Daniels1,2. 1. The University of Texas Graduate School of Biomedical Sciences at Houston 2. Departments of Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center 3. Departments of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center 4. Department of Obstetrics, Gynecology, and Reproductive Sciences, UT Health McGovern Medical School 5. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Abstract
Background: Mutations in the BRCA1 and BRCA2 genes predispose individuals to a significantly elevated risk for breast and ovarian cancers. Identification of these individuals allows for proper screening, management, and testing of at-risk relatives. NCCN has established clinical criteria for recommending BRCA1/2 testing. Patients and Methods: A retrospective chart review of 1,123 patients with breast cancer was performed to evaluate the positive predictive values (PPVs) of 14 individual criteria for predicting BRCA1/2 mutations. Results: Two criteria had PPVs significantly below 10%. Only 2 of 115 patients who were recommended for testing based solely on the criterion of "diagnosed with breast cancer at ≤45 years of age" had pathogenic mutations at a PPV of 1.6% (95% CI, 0.2%-6.0%). Additionally, 0 of 37 individuals who underwent testing based on the criterion, "diagnosed with breast cancer at any age with ≥2 close blood relatives with breast cancer at any age" tested positive (95% CI, 0%-9%). Overall, meeting >1 criterion has a PPV of 12%, whereas meeting only 1 criterion has a PPV of 3.2% (95% CI, 1.6%-5.7%), significantly below 10% (P<.0001) for predicting BRCA1/2 positivity. Conclusions: Patients with breast cancer meeting >1 criterion constitute a population significantly enriched for BRCA1/2 mutations, whereas those meeting only 1 criterion test positive at a rate similar to unselected patients with breast cancer. These data will inform ongoing discussions regarding how to best implement BRCA1/2 genetic testing.
Background: Mutations in the BRCA1 and BRCA2 genes predispose individuals to a significantly elevated risk for breast and ovarian cancers. Identification of these individuals allows for proper screening, management, and testing of at-risk relatives. NCCN has established clinical criteria for recommending BRCA1/2 testing. Patients and Methods: A retrospective chart review of 1,123 patients with breast cancer was performed to evaluate the positive predictive values (PPVs) of 14 individual criteria for predicting BRCA1/2 mutations. Results: Two criteria had PPVs significantly below 10%. Only 2 of 115 patients who were recommended for testing based solely on the criterion of "diagnosed with breast cancer at ≤45 years of age" had pathogenic mutations at a PPV of 1.6% (95% CI, 0.2%-6.0%). Additionally, 0 of 37 individuals who underwent testing based on the criterion, "diagnosed with breast cancer at any age with ≥2 close blood relatives with breast cancer at any age" tested positive (95% CI, 0%-9%). Overall, meeting >1 criterion has a PPV of 12%, whereas meeting only 1 criterion has a PPV of 3.2% (95% CI, 1.6%-5.7%), significantly below 10% (P<.0001) for predicting BRCA1/2 positivity. Conclusions: Patients with breast cancer meeting >1 criterion constitute a population significantly enriched for BRCA1/2 mutations, whereas those meeting only 1 criterion test positive at a rate similar to unselected patients with breast cancer. These data will inform ongoing discussions regarding how to best implement BRCA1/2 genetic testing.
Authors: Anna C Beck; Haimiao Yuan; Junlin Liao; Pamela Imperiale; Krysten Shipley; Lillian M Erdahl; Sonia L Sugg; Ronald J Weigel; Ingrid M Lizarraga Journal: Am J Surg Date: 2019-06-19 Impact factor: 2.565