To determine if there is a heritable predisposition for breast or ovarian cancer in adults with any of the following:
• Breast cancer diagnosed at age 50 or younger
• Ovarian cancer
• Multiple primary breast cancers either in the same breast or opposite breasts
• Male breast cancer
• Triple-negative (estrogen receptor negative, progesterone receptor negative, and HER2/neu [human epidermal growth factor receptor 2] negative) breast cancer
• Pancreatic cancer with breast or ovarian cancer in the same individual or on the same side of the family
• Ashkenazi Jewish ancestry
• Two or more relatives with breast cancer, one under age 50
• Three or more relatives with breast cancer at any age
When a relative has been previously tested, see Familial Mutation, Targeted Sequencing (2001961).
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 2 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Female carriers of BRCA1 mutations have a breast cancer risk of 57 percent and ovarian cancer risk of 40 percent by age 70. Female carriers of BRCA2 mutations have a breast cancer risk of 49 percent and ovarian cancer risk of 18 percent by age 70. BRCA1 mutation carriers may also be at increased risk for fallopian, peritoneal, cervical, uterine, and pancreatic cancer. BRCA2 mutation carriers may be at increased risk for pancreatic, stomach, gallbladder, bile duct, and melanoma cancers. Men with BRCA1 mutations are at increased risk for breast cancer and possibly pancreatic, prostate, and testicular cancers while male carriers of BRCA2 mutations are at increased risk for breast, pancreatic and prostate cancers.
Prevalence: 1 in 500 individuals have a BRCA1 or BRCA2 mutation; 5-10 percent of breast cancer and 10-15 percent of ovarian cancer are caused by germline BRCA1 or BRCA2 mutations.
Inheritance: Autosomal dominant.
Cause: Pathogenic germline mutations in several genes cause hereditary breast and ovarian cancer (HBOC) syndrome. Mutations in tumor suppressor genes, BRCA1 and BRCA2, are causative for the majority of HBOC.
Genes Tested: BRCA1 and BRCA2.
Clinical Sensitivity: 20-60 percent of HBOC.
Methodology: Bidirectional sequencing and multiplex ligation-dependent probe amplification (MLPA) of the entire coding regions and intron-exon boundaries of the BRCA1 and BRCA2 genes.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Rare diagnostic errors can occur due to primer or probe site mutations. Regulatory region mutations and deep intronic mutations will not be detected. Genes causing HBOC syndrome, other than BRCA1 and BRCA2, are not tested. Deletion/duplication breakpoints will not be determined.
|Component Test Code*||Component Chart Name||LOINC|
|2011950||BRCA Seq, Del/Dup Specimen||31208-2|
|2011951||BRCA Seq, Del/Dup Interp||59041-4|