Breast cancer develops when cells of the breast become mutated and fail to respond to normal growth regulation from the body. The cells begin to divide uncontrollably, leading to the formation of a tumor. A number of genes control normal cell proliferation, either by promoting or inhibiting proliferation, which become mutated in the cancer cells to facilitate constant cell proliferation. A number of genetic mutations have found to be especially important in the development of breast cancer and increase an individual's chance of developing breast cancer.
BRCA
Mutations to the BRCA genes, called BRCA1 and BRCA2, are associated with breast cancer. BRCA1 and BRCA2 are called tumor suppressor genes-they prevent the development of cancer. Both genes must be mutated for the development of cancer. An individual will usually inherit a mutation in one of the genes from one of her parents and acquire mutation to the other gene throughout her life to develop cancer.
According to the Ohio State University Medical Center, inheriting a mutated form of BRCA1 or BRCA2 puts an individual at a 50 to 85 percent change of developing breast cancer, and also increases the risk of developing other cancers like melanoma, ovarian cancer, or stomach cancer.
HER2
Another gene commonly involved in breast cancer is the HER2 gene, which creates the HER2 protein. HER2 is a protein found on the surface of normal cells, which signals for the cell to grow and divide. Under normal conditions, the activity of HER2 is partially regulated by the presence of specific factors released by the body that tell the cell to grow.
In breast cancer, HER2 becomes overproduced, so it is always telling the cell to divide, regardless of signals from the body. This is likely due to genetic mutations in parts of the DNA that regulate how much HER2 is generated within the cells. The breast cancer therapeutic Herceptin is targeted to treat breast cancers which over-produce HER2 .
FGFR2
Mutations to the FGFR2 gene are also involved in the development of breast cancer. Similarly to HER2, FGFR2 is found on the surface of cells and responds to growth signals from the body to tell the cell to divide. In breast cancer, too much FGFR2 is produced or FGFR2 is mutated, leading to constant signals telling the cell to divide, leading to the formation of a tumor.
In a 2008 study published in the American Journal of Human Genetics, Dr. A. Antoniou studied small changes in the FGFR2 gene in breast cancer patients, and found that small modifications of the gene caused over-production of the FGFR2 protein, leading to cancer. The study also found that mutations to FGFR2 had an enhanced effect on cancer development in patients carrying other mutations, such as mutations to BRCA1 or BRCA2. Therapeutics targeting FGFR2 are effective in helping to treat breast cancer.
References
- Ohio State University Medical Center: Hereditary Breast Ovarian Cancer Syndrome (BRCA1 / BRCA2)
- University of Pennsylvania: Her-2/neu and Its Significance: Science in Action: Part I
- PubMed: Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers.
