HER2 is a protein found on the surface of cells, playing a role in their growth and division. In certain cancers, particularly breast cancer, understanding the status of this protein is a standard part of the diagnostic process. Testing for HER2 helps medical professionals determine the most effective treatment approach for an individual’s specific cancer. This initial testing provides valuable information that guides subsequent therapeutic decisions.
Understanding HER2 and Its Role
HER2, which stands for human epidermal growth factor receptor 2, is a protein located on the outer membrane of all human cells. Its normal function involves receiving signals that instruct cells to grow, divide, and repair themselves. These signals are crucial for the healthy development and maintenance of tissues throughout the body.
In some cancers, the gene responsible for producing HER2 can become overactive or amplified. This amplification leads to an excessive number of HER2 proteins on the surface of cancer cells. With too many HER2 proteins, the cells receive an abundance of growth signals, causing them to multiply uncontrollably and form tumors. This uncontrolled proliferation is a hallmark of aggressive cancer growth.
Determining the HER2 status of a tumor is a significant step in cancer diagnosis and treatment planning. It serves as both a prognostic marker, indicating how aggressive the cancer might be, and a predictive marker, suggesting how likely the cancer is to respond to specific therapies.
The Meaning of HER2 2+
HER2 status is typically assessed through a laboratory test called immunohistochemistry (IHC), performed on a tissue sample from the tumor. This test measures the amount of HER2 protein on cancer cells. Results are reported using a scoring system, ranging from 0 to 3+. A score of 0 or 1+ indicates a low amount of HER2 protein, classifying the tumor as HER2-negative.
A score of 3+ signifies a high level of HER2 protein, definitively classifying the tumor as HER2-positive. When an IHC test yields a HER2 2+ score, it is considered an “equivocal” or “borderline” result. This means that the amount of HER2 protein detected is neither clearly low nor clearly high enough to make a definitive determination.
Consequently, a HER2 2+ IHC result is not considered definitively positive or negative. It indicates that further, more precise testing is required to confirm the tumor’s true HER2 status. This additional testing is necessary because the equivocal nature of the 2+ score means the tumor could either have a moderate, non-amplified level of HER2, or it could have a level that, while not reaching 3+ by IHC, still indicates gene amplification.
Next Steps After a HER2 2+ Result
When an IHC test for HER2 produces a 2+ result, a confirmatory test becomes necessary to establish the definitive HER2 status of the tumor. Fluorescence In Situ Hybridization (FISH) is widely recognized as the gold standard for this purpose. This test examines the number of HER2 gene copies within the cancer cells’ DNA.
FISH works by using fluorescent probes that bind specifically to the HER2 gene sequences in the tumor cells. Under a microscope, researchers can then count the number of HER2 gene copies relative to the number of copies of a control gene.
The FISH test for a 2+ IHC result can lead to two distinct outcomes. The cancer may be determined to be HER2-positive, meaning the HER2 gene is amplified, even if the protein expression wasn’t definitively high by IHC. Conversely, the test might show the cancer is HER2-negative, indicating the gene is not amplified, despite the moderate protein expression.
Obtaining this definitive FISH result is of paramount importance for guiding appropriate treatment decisions. Without it, clinicians cannot accurately determine if a patient’s cancer will respond to specific targeted therapies.
Treatment Implications of HER2 Status
The final, confirmed HER2 status, determined by the FISH test after an initial 2+ IHC result, directly dictates the treatment strategy for the cancer. If the cancer is definitively confirmed as HER2-positive by FISH, it becomes eligible for specific HER2-targeted therapies. These therapies, such as trastuzumab and pertuzumab, are monoclonal antibodies designed to specifically bind to the HER2 protein on cancer cells.
By binding to HER2, these drugs block the growth signals that drive uncontrolled cell proliferation. They can also mark HER2-positive cancer cells for destruction by the immune system. These targeted therapies have significantly improved outcomes for patients with HER2-positive cancers, offering a highly effective and precise treatment approach. However, these therapies are only beneficial for cancers that exhibit HER2 gene amplification.
Conversely, if the cancer is confirmed as HER2-negative by FISH, it will not respond to HER2-targeted drugs. In such cases, the treatment approach will involve other standard therapies, such as chemotherapy, hormone therapy, or immunotherapy. This personalized approach, guided by the precise HER2 status, ensures that each patient receives the most appropriate and potentially life-saving treatment regimen.