Oncogenes and Breast Cancer

Proto-oncogenes are normal genes involved in making cells differentiate and divide. When these genes are mutated, they are then called oncogenes. Proto-oncogenes involved in breast cancer are mostly those that cause more cell division by making the cell cycle go faster and accelerate. They are involved in pushing cell division harder, stronger and faster.

One of the proto-oncogenes is related to the epidermal growth factor receptor. This receptor plays a vital role at certain times of the life cycle, such as puberty, when big changes are going on with body growth, wherein a protein known as epidermal growth factor functions to promote cell growth. This protein binds to an epidermal growth factor receptor and signals the cell to grow. When the proto-oncogene for the receptor is over expressed, it doesn't wait for the epidermal growth factor receptor to tell it to grow. Instead, cells begin to grow independently, just like getting stuck in the "ON" position.

Another type of epidermal growth factor receptor is a subtype, the epidermal growth factor receptor 2. This receptor is more commonly known as Her-2/neu oncogene. The type of genetic alteration that Her-2/neu has in breast cancer is known as amplification. Instead of having only one copy during cell division, the cell makes numerous copies of this gene, about ten to sixty times more. Either the gene over expression or the extra protein can be measured in a woman's cancer by examining the cancer tissue that has been resected. Since Her-2/neu oncogene encodes a growth factor receptor, it functions in signaling the cells to grow faster and faster, although it is not involved in cancer invasiveness. About 70 to 80 percent breast precancers have over expression of Her-2/neu oncogene. The cancer cells are still contained within the breast duct, but they have been programmed to grow much faster because of the over expression of such oncogene. Although Her-2/neu oncogene was first identified in breast cancer, research is also being done to see if it is also involved in other cancer types such as lung, pancreas and ovary cancer.

For breast cancer to have an invasive nature, it needs more than one genetic alteration. So long as there's only over expression of Her-2/neu oncogene, the cancer will remain confined within the breast duct. If it requires other forms of genetic alterations, one that causes cancer cells to move out of the ductal region or make new blood vessels (angiogenesis), then it can spread. If the cancer patient has these invasive cancer alterations and one of the accelerated cancer growths, then it is worse. People with both of these genetic alterations have a worse prognosis than with only one type of alteration alone. Cancer not only requires excessive cancer cell proliferation, it also has to invade, grow new blood vessels and spread from the breast area.

One of the fascinating things that have happened in recent years is that there is now an antibody to counteract the Her-2/neu receptor, which can be given intravenously to breast cancer patients. It has quite a unique mechanism of action. It attaches only to cells with too much Her-2/neu receptor, not the normal ones, so that while it antagonizes Her-2/neu cells, it leaves the other cells unaffected. Unlike chemotherapy, with which case most dividing cells are destroyed, it is a targeted therapy. So far, this treatment has been used only in metastatic breast cancer, but it has implications for disease that hasn't spread yet.