BRCA and Beyond

Ambry is pleased to offer multiple BRCA testing options including comprehensive sequencing and deletion/duplication analyses of BRCA1 and BRCA2 and numerous multigene panels.

The BRCA1/2 VUS rate (combined) for our first 1000 reported cases was just under 5% and has consistently declined to a current level of 3.64%

Hereditary breast-ovarian cancer (HBOC) syndrome is an autosomal dominant cancer predisposition syndrome caused by germline BRCA1/2 mutations. Mutations in these two highly penetrant genes increase the chance for cancer of the breast, ovaries and fallopian tubes, pancreas and prostate.3,4 Studies suggest female BRCA1 mutation carriers have between a 57-87% risk to develop breast cancer and between a 39-40% risk to develop ovarian cancer by age 70.4-9 Similarly male BRCA1 mutation carriers have a cumulative breast cancer risk of 1.2% by age 70.10,11

Similar studies suggest female BRCA2 mutation carriers have between a 45-84% risk to develop breast cancer and between an 11-18% risk to develop ovarian cancer (including primary peritoneal and fallopian tube) by age 70.7-9,14 Male BRCA2 mutation carriers have up to a 15% prostate cancer risk and a cumulative breast cancer risk of 6.8% by ages 65 and 70 respectively.10-14 Furthermore, BRCA1/2 mutation carriers are at an increased risk for melanoma and cancer of the pancreas, gall bladder, bile duct and the stomach.15 Cancer risks are further modified by family history, reproductive choices, lifestyle and environmental factors and other genetic factors.

BRCA1/2 mutations are more common in individuals of Ashkenazi Jewish (AJ) descent, with a carrier frequency of 1/40 or 2.6%4,5 compared to a frequency of 0.2% or 1/500 in the non-AJ general population. Three founder mutations: BRCA1 gene c.68_69delAG (BIC: 185delAG) and c.5266dupC (BIC: 5382insC) and one in BRCA2 c.5946delT (BIC: 6174delT), account for up to 99% of identified AJ mutations.4,5 BRCA1 185delAG has a frequency of 1% and attributes to 16-20% of breast cancer cases diagnosed before 50 years-of-age; BRCA1 5382insC with a frequency of 0.13%; and BRCA2 6174delT with frequency of 1.52% in the AJ population and attributes to 15% of breast cancer cases diagnosed before 50 years-of-age.4,5

2-4 Week Turnaround Time on All "Next" Panels 
(Effective November 3rd 2014)


1. National Comprehensive Cancer Network. Clinical practice guidelines in oncology, genetic/familial high-risk assessment: breast and ovarian. Available at: 2010. Accessed 5.29.13.

2. American Society of Clinical Oncology Policy Statement Update: Genetic Testing for Cancer Susceptibility. J Clin Oncol. 2003 Jun 15; 21(12):2397-406.

3. Rohini, R., Chun, J., Powell, S. (2012). BRCA1 and BRAC2: different roles in a common pathway of genome protection. Nature,12:68-78.

4. Ferla, R., et al. (2007). Founder mutations in BRCA1 and BRCA2 genes. Annals of Oncology,18;(Supplement 6):vi93-vi98.

5. Janavivius, R. (2010). Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. EPMA Journal,1:397-412.

6. Tulinius, H., et al. (2002). The effect of a single BRCA2 mutation on cancer in Iceland. J Med Genet,39:457 -462

7. Ford, D., et al. (1998). Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Amer Jrn Hum Genet, 62(3):676-689. 

8. Antonious, A., et al. (2003). Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am Jrn Hum Genet, 72(5):1117-1130. 

9. Chen, S., et al. (2007). Meta-analysis of BRCA1 and BRCA2 penetrance. Jrn Clin Oncol, 25(11):1329-1333. 

10. Tai, Y., et al. (2007). Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. Jrn Natl Canc Inst, 99(23):1811-1814. 

11. Thompson, D., et al. (2002). Cancer incidence in BRCA1 mutation carriers. Jrn Natl Canc Inst, 94(18):1358-1365. 

12. Kote-Jerai, Z., et al. (2011). BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. Br Jrn Cancer, 105(8):1230-1234. 

13. Folkins, A., Longacre, T. (2013). Hereditary gynecological malignancies: advances in screening and treatment. Histopathology,62:2-30.

14. Mahoney-Shannon, K., and Chittenden, A. (2012). Genetic testing by cancer site: breast. The Can Jrn, 18(4):310-319.

15. Van Asperen, C., et al. (2005). Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. Jrn Med Genet, 42(9):711-719.