What is HER2?
HER2, or human epidermal growth factor receptor 2, is a protein that promotes cell growth. It is encoded by the ERBB2 gene. In some cancers, particularly breast and gastric cancers, the HER2 gene can become amplified, leading to an overexpression of the HER2 protein. This overexpression can cause cancer cells to grow and divide more rapidly than normal cells.
Why is HER2 Testing Important?
HER2 testing is crucial in the diagnosis and treatment planning for certain types of cancers. The presence of HER2 overexpression or gene amplification can influence the aggressiveness of the cancer and guide treatment options. Knowing a tumor’s HER2 status helps oncologists decide whether targeted therapies, such as trastuzumab (Herceptin), pertuzumab (Perjeta), and other HER2 inhibitors, may be effective.
How is HER2 Testing Performed?
There are primarily two methods for HER2 testing: Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH).
- IHC: This test measures the amount of HER2 protein on the surface of cells in a cancer tissue sample. The results are scored from 0 to 3+, with 0 and 1+ considered HER2-negative, 2+ as equivocal, and 3+ as HER2-positive.
- FISH: This test looks for HER2 gene amplification in the cancer cells. It uses fluorescent dyes to highlight the HER2 genes. A positive FISH test indicates HER2 gene amplification.
In cases where the IHC results are equivocal (2+), FISH testing is often used as a follow-up to confirm the HER2 status.
When Should HER2 Testing Be Done?
HER2 testing should be conducted at the time of initial cancer diagnosis, particularly for patients with invasive breast cancer or metastatic gastric cancer. It’s essential to determine the HER2 status early to tailor the most effective treatment plan. Repeat testing may be necessary if there is a significant change in the cancer’s behavior or if the initial biopsy was inadequate.
Who Should Be Tested for HER2?
Patients diagnosed with invasive breast cancer or metastatic gastric cancer should undergo HER2 testing. Additionally, those with recurrent or metastatic disease previously tested negative may be retested, as HER2 status can change over time.
What Are the Implications of HER2-Positive Results?
A HER2-positive result indicates that the cancer is likely to be more aggressive and may respond well to HER2-targeted therapies. These therapies can significantly improve outcomes by slowing disease progression and increasing survival rates. However, HER2-positive cancers may also have a higher risk of recurrence.
- Trastuzumab (Herceptin): A monoclonal antibody that binds to the HER2 protein and inhibits cancer cell growth.
- Pertuzumab (Perjeta): Often used in combination with trastuzumab and chemotherapy.
- Ado-trastuzumab emtansine (Kadcyla): A conjugate of trastuzumab and a chemotherapy drug.
- Lapatinib (Tykerb): A small molecule inhibitor that targets both HER2 and EGFR.
These treatments can be used alone or in combination, depending on the specific case and the oncologist’s judgment.
Challenges and Limitations of HER2 Testing
While HER2 testing is a powerful tool, it is not without its challenges. Variability in test interpretation, particularly with IHC, can lead to inconsistent results. It is also possible for HER2 status to change over the course of the disease, necessitating repeat testing. Ensuring accurate and consistent testing requires strict adherence to standardized protocols and guidelines.Future Directions
Ongoing research aims to enhance the accuracy of HER2 testing and develop new HER2-targeted therapies. Advances in genomic profiling and molecular diagnostics may provide more comprehensive insights into HER2 status and its role in cancer progression, ultimately leading to more personalized and effective treatment strategies.
