What is hereditary breast cancer?

Cancer development is a complex process. If certain genes are mutated and do not give cells proper instructions about when to grow and divide, then cancer could develop. Environmental factors, such as UV light, tobacco and diet can increase mutation rates. Some of these mutations will be repaired, but some mutations will not. These mutations will be present in some cells in the body and this will increase the risk of cancer development.

However in families with hereditary forms of cancer, a mutation is present in a very important gene and is present in all cells in the body. Inheriting a cancer-causing mutation in one of the cancer-associated genes does not mean that cancer will definitely occur. It means only that your risk is higher than for someone who does not carry such a mutation in their cells.

Hereditary breast cancer is most commonly caused by inherited mutations in BRCA1 and BRCA2 genes. Breast cancer is unfortunately quite common among American women, with about 1 in 8 (13%) women developing breast cancer at some point in their lifetime. More than 200,000 cases of breast cancer are diagnosed each year in the United States, affecting mostly women after age 50. Men can also develop breast cancer although such cases are rare; about 2,000 cases are diagnosed each year in the U.S.. Although most breast cancer occurs by chance however about 10% is inherited. BRCA mutations occur in about 1 in 400-500 in the general population. BRCA1/2 mutations are found more frequently in certain ethnic groups, including Ashkenazi (Eastern European) Jewish and French Canadian background. The Ashkenazi Jewish population has a high risk for having BRCA1/2 mutations with a frequency of 1 in 40.

Characteristics of Families with BRCA mutations

Families with BRCA1 & BRCA2 mutations generally have one or more of the following:

  • Several close relatives with breast cancer
  • Early onset breast cancer (under 50 years of age)
  • Bilateral (cancer in both breasts) or multiple primary breast cancer
  • Triple-negative (ER-/ PR-/ HER2/neu-) breast cancer diagnosed under 60 years of age
  • Family or personal history of both breast and ovarian cancer
  • Increased frequencies of other cancers such as prostate and pancreatic cancer
  • Male breast cancer at any age
  • Ashkenazi (Eastern European) Jewish ethnic background
It is important to be aware that hereditary breast or ovarian cancer can be inherited from either the maternal (mother's) or paternal (father's) side of the family.


Effect of BRCA1/2 Mutations on Cancer Risk

All women have some risk of developing breast or ovarian cancer at some point in their lives. Having a BRCA1 or a BRCA2 mutation increases this risk. Women carrying a BRCA1/2 mutation also have an increased risk of pancreatic cancer, while men who have a BRCA1/2 mutation have an increased risk of breast, prostate and pancreatic cancer (Table 1).



What is BrcaDx ClearTM?

BrcaDx ClearTM is a next-generation sequencing assay designed for BRCA1/2 mutation testing for individuals who have a personal and/or family history of a hereditary breast and ovarian cancers. Testing includes sequencing, deletion and duplication analysis of the BRCA1 and BRCA2 genes. We use next-generation sequencing (NGS) technology to identify variants in the coding regions of BRCA1 and BRCA2 genes. The identified variants are classified according to the guidelines for sequence variant interpretation of the American College of Medical Genetics and Genomics (ACMG). Variant classification categories include pathogenic, likely pathogenic, variant of unknown significance (VUS), likely benign, and benign with likely benign and benign variants excluded from the report.

  • Pathogenic variants - Genetic changes with known clinical significance that is associated with an increased risk of hereditary cancer.
  • Likely pathogenic variants – Genetic changes that have some preliminary clinical data indicating an association with hereditary cancer but not sufficient to make a definitive determination of pathogenicity.
  • Variants of uncertain significance (VUS) – Genetic changes with either conflicting or no supporting data to determine their pathogenicity.
  • Negative Result – No variant of clinical or uncertain significance was detected. Negative result does not eliminate the risk of developing cancer. Benign variants that have sufficient evidence to be considered of no clinical significance and likely benign variants that are not likely to increase the risk of cancer will not be shown on the report.

BrcaDx ClearTM genes

GENE LIST
BRCA1 BRCA2
Click on any gene to view its definition

BRCA1 - This gene provides instructions for making a protein that acts as a tumor suppressor. Tumor suppressor proteins help prevent cells from growing and dividing too rapidly or in an uncontrolled way.

The BRCA1 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA1 protein interacts with several other proteins to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and they also occur when chromosomes exchange genetic material in preparation for cell division. By helping to repair DNA, the BRCA1 protein plays a critical role in maintaining the stability of a cell's genetic information.

Research suggests that the BRCA1 protein also regulates the activity of other genes and plays an essential role in embryonic development. To carry out these functions, the BRCA1 protein interacts with many other proteins, including other tumor suppressors and proteins that regulate cell division.

BRCA2 - This gene provides instructions for making a protein that acts as a tumor suppressor. Tumor suppressor proteins help prevent cells from growing and dividing too rapidly or in an uncontrolled way.

The BRCA2 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and they also occur when chromosomes exchange genetic material in preparation for cell division. By helping to repair DNA, the BRCA2 protein plays a critical role in maintaining the stability of a cell's genetic information.

Researchers suspect that the BRCA2 protein has additional functions within cells. For example, the protein may help regulate cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. Researchers are investigating the protein's other potential activities.