Ambry Genetics Testing

BREASTNEXT

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BreastNext^TM is a next generation (next-gen) sequencing panel that simultaneously analyzes 18 genes that contribute to increased risk for breast cancer including BRCA1 and BRCA2.

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Please note, all samples received starting October 18, 2013 for BreastNext and OvaNext will automatically include NF1 and RAD51D gene sequencing and deletion/duplication analyses at no additional cost. Additionally, Ambry will contact clinicians to discuss any clinically-significant NF1and RAD51D incidental findings on all in-house samples.

Ambry utilizes next generation sequencing to offer a comprehensive testing panel for hereditary breast and/or ovarian cancer, including BRCA1 and BRCA2. Genes on this panel include ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MRE11A, MUTYH, NBN, NF1, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11 and TP53. Gross deletion/duplication analysis is performed for all 18 genes. Specific-site analysis is available for individual gene mutations known to be in the family.

• Cancer Test Requisition & Pre-Verification Form
• Cancer Multi-Gene Consent Form
• BreastNext Patient Guide
• White Paper: Clinical Adoption of Hereditary Breast Cancer Panel
• Overview of Ambry's Technology
• BreastNext White Paper

Disease Name 

Cancer, Breast

Hereditary Breast Cancer

Disease Information 

Breast cancer is a disease in which cells in the breast become abnormal and multiply to form a malignant tumor.  Breast cancer is the most common cancer in women in developed countries, affecting about 1 in 8 (~12.29%) women in her lifetime.¹ The NCI estimates that there will be approximately 227,000 new cases of female breast cancer and 2,200 new cases of male breast cancer diagnosed in the U.S. in 2012.²

Breast cancer is a complex, multifactorial disease in which there is a strong interplay between genetic and environmental factors.  Approximately 5-10% of breast cancer is thought to be due to a specific hereditary cause and an additional 20-30% is estimated to be 'familial,' meaning there is more breast cancer in a family than you could expect by chance.  Hereditary breast cancers tend to occur earlier in life than non-inherited sporadic cases and are more likely to involve both breasts.  Other risk factors for breast cancers include age, gender, reproductive and menstrual history, alcohol, radiation, high body mass index, and benign breast disease, such as atypical ductal hyperplasia (ADH) and lobular carcinoma in situ (LCIS).²

While hereditary breast cancer can be explained by mutations in BRCA1 and BRCA2 ~25–50% of the time, additional genes associated with hereditary breast cancer are emerging.^3-5 Studies demonstrate that mutations in the genes on the BreastNext panel can confer an estimated 25–70% lifetime risk for breast cancer.  Some of these genes have also been associated with increased risks for other cancers, such as pancreatic cancer with PALB2, ovarian cancer with RAD50, and sarcomas with TP53.

BreastNext Panel Genes

 

ATM is a gene classically associated with an autosomal recessive condition called ataxia-telangiectasia (AT). AT is an autosomal recessive disorder characterized by progressive cerebellar ataxia with onset between ages one and four, telangiectases of the conjunctivae, oculomotor apraxia, immune defects, and a predisposition to malignancy, particularly leukemia and lymphoma. Heterozygous carrier females also have an estimated 2-4 fold increased risk for breast cancer.⁷ Recent studies have also reportedATM germline mutations in individuals with familial pancreatic cancer. In one of these studies, ATM mutations were identified in 4.6% (4/87) of families with more than 3 affected members.³² The exact lifetime pancreatic cancer risk for ATM mutation carriers has not yet been established.

 

BRCA1 and BRCA2 are tumor suppressor genes. Mutations in these two highly penetrant genes increase the chance for cancer of the breast, ovaries and fallopian tubes, pancreas and prostate. 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. Similarly male BRCA1 mutation carriers have a cumulative breast cancer risk of 1.2% by age 70.

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. Male BRCA2 mutation carriers have up a 15% prostate cancer risk and a cumulative breast cancer risk of 6.8% by ages 65 and 70 respectively.

Furthermore, BRCA1/2 mutation carriers are at an increased risk for melanoma and cancer of the pancreas, gall bladder, bile duct and the stomach. Cancer risks are further modified by family history, reproductive choices, lifestyle and environmental factors and other genetic factors.

BARD1, BRIP1, MRE11A, NBN, RAD50, and RAD51C are genes involved in the Fanconi anemia (FA)–BRCA pathway, which is critical for DNA repair by homologous recombination and interact in vivo with BRCA1 and/or BRCA2.^3,8-10 Mutations in these genes are estimated to confer up to a 4 fold increase in breast cancer risk, and mutations in each have been reported in at least 1 identified case of ovarian cancer to date.¹¹

CHEK2 is a gene that receives signals from damaged DNA, transmitted to CHEK2 via ATM.  Known substrates of CHEK2 include BRCA1, BRCA2 and TP53, which have all been implicated in cellular processes responsible for the maintenance of genomic stability. Multiple studies indicate that mutations in the CHEK2 gene confer an increased risk of developing many types of cancer including breast, prostate, colon, thyroid, and kidney. Mutations are more likely to be found among women with bilateral versus those with unilateral breast cancers. A female carrier of a CHEK2 mutation has approximately a 2 fold increase in lifetime breast cancer risk and has a 1% risk per year of developing a second breast primary cancer. Ovarian cancer risk has also been suggested.^11-15