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How BRCA Genes Work


Acquired Mutations: HER2- and Estrogen-positive Cancers
A medical illustration shows a cancerous tumor within the female breast.
A medical illustration shows a cancerous tumor within the female breast.
© Visuals Unlimited/Corbis

Sometimes the cells making up breast tissue can begin to grow unchecked, crowding out normal milk-producing cells. As these uninhibited bullies push and shove their way around, they form a mass of tissue known as a lump or tumor. If the lump stays contained and doesn't invade surrounding lobules or other parts of the body, it's classified as benign. If, however, it continues to invade the surrounding breast and spreads to the lymph nodes, it's classified as malignant or cancerous.

Scientists now know that cancer is caused by damage to DNA -- a mutation -- in genes that regulate cell growth and division. Many mutations arise when someone is exposed to certain environmental conditions, such as radiation. Breast cells are not immune to these acquired (as opposed to inherited) mutations. In fact, two types of breast cancer occur when DNA becomes damaged as a result of environmental carcinogens or viruses.

The first type affects how hormones, like estrogen, interact with breast cells. During a woman's monthly menstrual cycle, estrogen levels surge in the breast to prepare the tissue to make milk. Estrogen molecules bind to receptors in the breast cells, triggering the cells to proliferate. If a woman doesn't become pregnant, all of these extra milk-producing cells deteriorate and die. Sometimes, though, this proliferation process can go haywire if certain breast cells harbor damaged DNA. When these compromised cells receive the signal from estrogen, they multiply as they should, but they fail to stop and don't die at the end of a cycle.

Another acquired mutation affects the gene coding for a protein known as human epidermal growth factor receptor 2, abbreviated HER2. Normally, HER2 proteins on the surface of breast cells respond to growth factors -- chemicals that tell a breast cell how to grow properly. HER2 proteins receive these factors, then shuttle the instructions inside the cell. If the DNA of the HER2 gene becomes damaged, however, its activity can rev up to dangerous levels. It can produce too much HER2 protein and, as a result, cause unchecked growth of breast cells.

Neither estrogen-positive nor HER2-positive cancers can be passed on to other family members because the mutations affect only breast cells. That's not the case with inherited breast cancer. In this form of the disease, a mutation is carried in a parent's sperm or egg cells and passed, at fertilization, to his or her offspring. These mutations then appear in every cell of the body and predispose the person to developing cancer. Scientists have discovered several genes linked to inherited breast cancer, including the acronym nightmares p53, PTEN/MMAC1, CHEK2 and ATM. But the BRCA genes are the best known and perhaps the most intensely studied. In the next section, we'll take a closer look at the family tree of BRCA genes.