Date of Graduation
5-2015
Document Type
Thesis (MS)
Program Affiliation
Genetic Counseling
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Molly Daniels, MS
Committee Member
Banu Arun, MD
Committee Member
Carlos Barcenas, MD, MSc
Committee Member
Jennifer Litton, MD
Committee Member
Sarah Noblin, MS
Committee Member
Ashley Woodson, MS
Abstract
Hereditary Breast and Ovarian Cancer (HBOC) syndrome predisposes females with a BRCA1 or BRCA2 mutation to an up to 85% lifetime risk for breast cancer and an up to 40% lifetime risk for ovarian cancer. It is crucial for individuals with HBOC to be identified to allow for proper screening, management, and identification of at-risk family members in order to reduce mortality. The National Comprehensive Cancer Network (NCCN) has established clinical guidelines for when to recommend BRCA1/2 testing. A retrospective chart review of 1123 M.D. Anderson Cancer Center breast cancer patients was performed in order to evaluate the positive predictive values (PPVs) of 14 individual criterion for predicting a BRCA1/2 mutation. Two criteria had PPVs significantly below 10%. Only 2 of 115 patients recommended for testing based solely on the criterion of “diagnosed with breast cancer ≤45 years of age” tested positive for a pathogenic mutation at a PPV of 1.6% (0.2-6%, 95% CI), which is significantly below the clinical utility cut-off of 10% (p = 0.001). Additionally, 0 out 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 (0-9%, 95% CI). Overall, an individual who meets more than one criterion has a PPV of 12% while those who meet only one criterion has a PPV of 3.52%, which is significantly below 10% (p<.0001) for predicting BRCA1/2 positivity. This data can help provide more personalized risks and anticipatory guidance for patients in their decision to pursue genetic testing.
Keywords
NCCN, BRCA1, BRCA2, BRCA, genetic testing, hereditary breast and ovarian cancer