Breast Cancer
What Is Breast Cancer?
Most breast cancers begin in the milk ducts, narrow passageways that radiate throughout the breast. A few cells, for reasons that are not completely understood, start accumulating genetic mistakes that cause them to grow abnormally. Eventually the cells develop into DCIS (ductal carcinoma in situ). The good thing about dcis cells is that they haven't spread beyond the milk duct. The bad thing is that they are malignant. "Some people call DCIS precancer, but it's not precancer," says Dr. Dennis Slamon, director of breast-cancer research at the UCLA School of Medicine. "It's preinvasive. It's cancer that hasn't invaded outside the breast ducts."
After a tumor starts to break out of its milk duct, it's often still quite small. About the smallest tumor a mammogram can pick up is 0.5 cm to 1 cm (0.2 in. to 0.4 in.) in diameter. By contrast, the average cancers that are felt either by women or their physicians are around 2.5 cm, or about an inch. Even though mammograms still miss about 10% of all tumors, it's their ability to spot smaller tumors, which are generally easier to treat, that keeps women coming back for their annual appointment.
Once the cancer puts down roots in the lymph nodes, the prognosis gets worse. The lymph nodes act as a kind of sewer system for many types of toxins and wastes. Tumors growing in the lymph nodes have a greater chance of breaking off and traveling to the bones, brain, lungs or other parts of the body, where they can seed new growths, called metastases.
Breast Cancer and HER-2
The HER-2 gene is a portion of genetic code that exists in everyone. Also known as HER-2/neu and c-erbB2, this gene plays a key role in the regulation of normal oncogene cell growth. The HER-2 gene helps cells grow, divide and repair themselves. In a normal cell, one gene exists on each chromosome and normally a person will have two copies of this gene for every cell. But during the development of cancer, this gene may become amplified, meaning that it creates excess copies of itself due to a mechanism that is not yet understood. If extra copies of the HER-2 gene appear in a cell, the genes cause too many HER-2 proteins (receptors) to appear on the cell surface. This is referred to as HER-2 protein overexpression.
It is estimated that approximately 1 in 4 breast cancers have too many copies of the HER-2 gene, resulting in the over-production of protein receptors found on the surface of tumor cells. These special proteins bind with other circulating growth factors to cause uncontrolled tumor growth. HER-2 positive breast cancers tend to grow fast. But these tumors also may respond very well to anti-HER-2 antibody therapy (HERCEPTIN®) and also to increased doses of chemotherapies. There are two tests for HER-2, IHC (ImmunoHistoChemistry) and FISH (Fluorescence in situ Hybridization). The IHC test looks at the protein on the surface of the cell by staining the cell with an antibody. The protein on the surface of the cell can be affected by tissue formalin fixation onto the slide. This can cause inaccurate interpretation of IHC results. In addition, IHC testing is subjective: the reader must judge the degree of color change in the cell against a non-standardized chart. The fluorescence in situ hybridization test (FISH) is more accurate and reliable. It is good for all kinds of tissue: fresh, frozen, and those formalin fixed, paraffin embedded tissue. It is also good for stored formalin fixed paraffin embedded tissue samples too. The FISH test measures HER-2 gene abnormality at the stable DNA level (see What Is FISH). The FISH test "paints" the HER-2 genes inside the cell, so they may be accurately counted.
All in all, IHC has been shown to miss 15-20% of positive specimens (compared to Clinical Trial Assay, CTA), compared with less than 5% with FISH testing. The most accurate HER-2 assessment is important for you and your doctor, in order to make the most accurate therapy decisions.
"Nearly a third of women with breast cancer have tumors that overexpress HER-2"
HER-2/neu gene amplification is associated with aggressive breast cancers and a shorter overall survival.
Since 1984, Oncologist Dennis Slamon has been "obsessed with a molecule called HER-2, " which he believed "held the key to nothing less than curing breast cancer."
"Women with low-level amplification of the HER-2/neu oncogene in benign breast biopsies are more than twice as likely as women without gene amplification to develop breast cancer"
Additional Information
