According to the National Human Genome Research Institute, or NHGRI, hereditary breast cancer accounts for as much as 27 percent of all female breast cancer. The hereditary forms of breast cancers occur when a gene change, or mutation, linked to increased breast cancer risk passes from parent to child. A number of different inherited gene mutations exist that increase the risk to develop breast cancer later in life.
High Penetrant Single Genes
Of the 27 percent of breast cancer linked to inherited genetic mutations, perhaps 5 to 10 percent relate to inheriting a mutation in a single high penetrant gene. This means inheriting a mutation in one gene which confers a very high chance of developing breast cancer during adulthood.
Examples include the BRCA1 and BRCA2 genes. Each of these genes when mutated holds an increased risk for causing breast cancer later in life. According to the National Cancer Institute, women in the general population have about a 12 percent chance of developing breast cancer in their lifetime, whereas women with a mutation in the BRCA1 gene or BRCA2 gene have at least a 60 percent risk.
Other rarer high penetrant single genes exist, together attributing 5 percent to all hereditary breast cancer. A mutation in any of these genes markedly increases the risk for developing breast cancer, with specific percentages difficult to assess due to the rarity of the conditions.
Low Penetrant Single Genes
According to the NHGRI, at least half of hereditary breast cancers link to low penetrant gene mutations. These associate to breast cancer risk, but at markedly lower percentages than with the high penetrant genes.
CHEK2 when mutated increases the risk for breast cancer to perhaps as much as 36 percent. Another example includes the ATM gene. When the ATM gene inherited from the mother and the one inherited from the father both have mutations, the rare multi-organ condition ataxia-telangiectasia results. When only one gene mutation passes, the disorder does not manifest. But an increased risk for breast cancer occurs, with associated lifetime risk of about 24 percent.
Other single low penetrant genes associated with breast cancer exist. With moderate increase in risk and occurring in only a small proportion of the general U.S. population, all of these have limited clinical applicability.
Low Penetrant Multiple Genes
The largest percentage of hereditary breast cancer relates to changes in many low penetrant genes, although each accounts for only a small percentage of overall breast cancer. These low penetrant changes hold modest risk for breast cancer, perhaps increasing lifetime risk from 12 percent to 18 percent.
The testing for low penetrant multiple genes compares thousands of genes between women with breast cancer and women without breast cancer to identify predictors. The differences found might or might not reflect actual association with breast cancer, as other factors could be involved. Thus, the clinical relevance remains unknown, and although commercially available, this type of testing has little use in clinical care.
