1 in 8 women are affected by breast cancer in their lifetime


1 in 71 women are affected by ovarian cancer in their lifetime


80% of families with a pattern of breast and ovarian cancer have been attributed to BRCA1/2 mutations


Among women, breast cancer is the second leading cause of cancer death. One in eight women will be affected by breast cancer in their lifetime1.

Pathway Genomics’ BRCATrueTM is a next-generation sequencing test that searches for mutations in BRCA1 and BRCA2 genes. Having mutations in either the BRCA1 or the BRCA2 gene significantly increases a patient’s risk for breast, ovarian and other types of cancer2.

BRCATrueTM Advantage

  • Easy to interpret and clinically actionable results
  • Rapid 2-week turnaround time
  • Advanced variant classification


Below are the next-generation sequencing tests that Pathway Genomics offers for risk of hereditary breast cancer:
  1. BRCATrue™
  2. BRCATrue™ Ashkenazi Jewish (3-Site)
  3. BreastTrue™ High Risk Panel
  4. Single Site Testing

Reflex Options

  1. BRCATrue™ with reflex to BreastTrue™ High Risk Panel
  2. BRCATrue™ Ashkenazi Jewish (3-Site) with reflex to BRCATrue™


The Science and Technology Behind BRCATrueTM

Genomic DNA (gDNA) is extracted from the patient’s specimen and evaluated for quality and quantity using standard methodology and procedures. The gDNA is then processed to enrich the targeted gene regions (exons and exon flanking regions) in a PCR-based reaction. Massively parallel sequencing is carried out on the enriched target DNA to detect mutations in these regions. Additional Sanger DNA sequencing (capillary electrophoresis) is carried out in cases where targeted gene regions are insufficiently covered for variant detection. Sanger DNA sequencing is also carried out to confirm specific findings when mutations are detected. Large gene rearrangements (large deletions or duplications) within the BRCA1 and BRCA2 genes are detected using quantitative PCR (qPCR). Positive results are confirmed by array comparative genomic hybridization (aCGH).

Reported Genes


Acceptable Sample Types


The saliva sample collection kit includes one saliva collection device. Fill each tube up to the notch in the collection device.


The blood sample collection kit includes one 4ml lavender blood tube.

For more information about the sample collection kits listed above, please contact our client services department at (877) 505-7374 or To order sample collection kits, complete our online order form.

CPT Codes

81211: BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants in BRCA1

81213: Uncommon duplication/deletion variants


Classification System

Pathway Genomics classifies variants using a 5-tier system based on the American College of Medical Genetics (ACMG) guidelines. Likely Benign and Benign variants are not reported.

Mutations with known clinical significance and demonstrated to increase the risk of cancer

Likely Pathogenic
Genetic changes that have some preliminary clinical data suggesting an association with cancer but not sufficient to make a definitive determination of pathogenicity and associated cancer risk

Uncertain Pathogenicity (VUS) | Genetic changes with either conflicting data or no supporting data, thus a determination of pathogenicity cannot be made

Likely Benign
Genetic changes with strong but limited evidence to be classified as benign and are not likely to increase the risk for cancer

Genetic changes that are previously reported and have sufficient evidence to be classified as benign with no clinical relevance


Hereditary Breast and Ovarian Cancer

DNA changes (mutations) in the BRCA1 and BRCA2 genes can lead to significantly increased lifetime risks for breast and ovarian cancer. Mutations in BRCA1 and BRCA2 lead to a condition known as hereditary breast and ovarian cancer syndrome, or HBOC, which accounts for 5 to 7 percent of breast cancer cases3 and 8 to 13 percent of epithelial ovarian cancer cases4. However, BRCA1 and BRCA2 mutations account for up to 80 percent of breast and ovarian cancer in families with multiple cases of either disease5-7.



The BRCA1 (breast cancer 1, early onset) gene encodes a multifunctional protein that interacts with tumor suppressors, DNA repair proteins, cell cycle regulators, RNA polymerase II holoenzyme, transcription factors, corepressors, chromatin remodeling enzymes, and RNA processing factors. BRCA1, therefore, has a critical role in maintaining genomic stability and is involved in many cellular processes important in tumor biology, including DNA repair, cell cycle progression, and transcriptional regulation 3,10-15. Loss or inactivation of one copy of BRCA1 is thought to result in accumulation of mutations and structural changes in the genome, thereby increasing risk of cancer16.


The BRCA2 (breast cancer 2, early onset) gene encodes a protein with important roles in the DNA damage response and DNA repair pathways3. BRCA2 is a tumor suppressor protein that mediates recruitment of the RAD51 recombinase protein to DNA double-strand breaks3. The primary function of the BRCA2 protein is to facilitate homologous recombination, an important DNA repair mechanism in maintenance of genomic integrity 3,16 . Loss or inactivation of one copy of BRCA2 is thought to result in accumulation of mutations and structural changes in the genome, thereby increasing risk of cancer16.


BRCATrueTM High Risk Patient Criteria

The test is best suited for individuals with either a history of early onset breast or ovarian cancer or a strong family history of breast and/or ovarian cancer. Individuals with the following medical or family history factors should consider testing for mutations in BRCA1/2:

  • Early onset breast cancer (under 50 years of age)
  • Bilateral or multiple breast cancers
  • Diagnosed with both breast and ovarian cancer
  • Family history of breast and/or ovarian cancer
  • Two or more BRCA1 or BRCA2-related cancers in a single family member
  • Male breast cancer within family
  • Ashkenazi Jewish ethnic background

Clinical Utility of BRCA Testing

  • Guide decisions on prevention strategies (e.g. chemoprevention, prophylactic surgery)
  • Increase surveillance for breast cancer
  • Inform treatment decisions
  • Identify family members at increased risk

    Familial Studies Program

    In the process of sequencing the patient’s DNA, we may identify a likely pathogenic genetic variant, or a genetic variant with uncertain pathogenicity (VUS). To help understand the significance of these types of variants, and how the patient and family members may be affected, Pathway Genomics offers a Familial Studies Program. Testing additional family members for the same variant observed in your patient, and determining the correlation between cancer history and occurrence of the variant, may provide further insight into the clinical relevance of the variant.



  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA: a cancer journal for clinicians. Jan-Feb 2014;64(1):9-29.
  2. National Cancer Institute (NCI). Genetics of Breast and Ovarian Cancer (PDQ®). 2014; Accessed April 29, 2014.
  3. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection Nature reviews. Cancer. Jan 2012;12(1):68-78.
  4. Liu G, Yang D, Sun Y, et al. Differing clinical impact of BRCA1 and BRCA2 mutations in serous ovarian cancer. Pharmacogenomics. Oct 2012;13(13):1523-1535.
  5. Easton DF, Bishop DT, Ford D, Crockford GP. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. American journal of human genetics. Apr 1993;52(4):678-701.
  6. Smith EC. An overview of hereditary breast and ovarian cancer syndrome. Journal of midwifery & women’s health. Nov-Dec 2012;57(6):577-584.
  7. Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. American journal of human genetics. Mar 1998;62(3):676-689.
  8. Malone KE, Daling JR, Doody DR, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years. Cancer research. Aug 15 2006;66(16):8297-8308.
  9. John EM, Miron A, Gong G, et al. Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA : the journal of the American Medical Association. Dec 26 2007;298(24):2869-2876.
  10. Deng CX, Brodie SG. Roles of BRCA1 and its interacting proteins. BioEssays : news and reviews in molecular, cellular and developmental biology. Aug 2000;22(8):728-737.
  11. Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nature reviews. Cancer. Sep 2004;4(9):665-676.
  12. Dapic V, Monteiro AN. Functional implications of BRCA1 for early detection, prevention, and treatment of breast cancer. Critical reviews in eukaryotic gene expression. 2006;16(3):233-252.
  13. Yun MH, Hiom K. Understanding the functions of BRCA1 in the DNA-damage response. Biochemical Society transactions. Jun 2009;37(Pt 3):597-604.
  14. Huen MS, Sy SM, Chen J. BRCA1 and its toolbox for the maintenance of genome integrity. Nature reviews. Molecular cell biology. Feb 2010;11(2):138-148.
  15. Millot GA, Carvalho MA, Caputo SM, et al. A guide for functional analysis of BRCA1 variants of uncertain significance. Human mutation. Nov 2012;33(11):1526-1537.
  16. Petrucelli N, Daly MB, Feldman GL. BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews(R). Seattle (WA)1993.