The Role of HER2 in Breast Cancer
Human Epidermal growth factor Receptor 2 (HER2) is the functional name of a protein also known as receptor tyrosine-protein kinase erbB-2. This protein is found in the membranes of human cells where it plays a role in normal cell growth, but is over expressed in cancer patients, especially for breast and certain subtypes of lung cancer.
Breast cancers that over express HER2 are among the most malignant and have a poorer prognosis, so early detection of this biomarker is important for patient outcomes and quality of life management. Unlike certain ‘cancer antigens’ that play no part in the course of the disease, ERBB2 / HER2 isn’t just a biomarker, and high levels of HER2 play a significant role in the course of breast cancer.
Not all cancers express HER2 to an abnormal degree, but in some breast cancers the ERBB2 gene is over expressed, leading to an excessive production of HER2 protein receptors on the surface of breast cells. This contributes to uncontrolled cell growth, worsening the prognosis. Testing serum levels of HER2 allow physicians to classify breast cancer patients into four categories, based on the extend of HER2 expression.
Broadly speaking, the more HER2 expressed, the poorer the prognosis, an unsurprising finding since HER2 plays a direct role in the progression of breast cancer. Fortunately, specific treatments can also be targeted against the effects of the protein. By using HER2 testing kits, patients can be categorised early and given a more accurate prognosis, helping to improve both quality of life and eventual clinical outcomes.
HER2 receptors are part of a family of cell surface receptors that respond to growth factors, compounds that facilitate cell growth and are seen in wound healing and many other processes in the body. When HER2 receptors bind to specific growth factors, they activate signalling pathways that regulate cell growth, survival, and division. Over expression of HER2 can lead to aberrant activation of these pathways, promoting tumour growth where breast tissue expands in an uncontrolled fashion. Breast cancers that over express HER2 tend to be more aggressive and have a poorer prognosis compared to other types of breast cancer: they may grow and spread more quickly, making them more difficult to treat, so physicians will use the presence of elevated HER2 levels to guide treatment options and manage patient expectations.
This means HER2 can be used as a biomarker for the progression of breast cancer, despite not being present in all cases. Breast cancer is not a single disease, instead a constellation of subtypes with different clinical outcomes and differing prognoses, with biomarkers providing physicians with a method for identifying each subtype.
Biomarker testing plays a critical role in identifying patient outcomes early and can take multiple forms. Often a biomarker is a protein expressed at a higher concentration, or in an unusual or mutated form, uniquely in cancer patients or a subtype of them. Cancer antigens are often enzymes that are over expressed by tumour cells, or which leave telltale signatures in the blood of cancer patients and form a subtype of the broader category of biomarkers. Though many biomarkers are molecules such as enzymes, physical biomarkers also exist, detected via imaging or physical examination. Biomarkers do not necessarily play a role in the progression of disease, as HER2 does, but sometimes are simply side-effects of the underlying malignant process.
Because HER2 has a role in the progression of breast cancer, targeted therapies exist such as trastuzumab, a monoclonal antibody, alongside several other HER2-targeted drugs. These drugs specifically inhibit the activity of HER2 receptors, helping to slow down or stop the growth of HER2-positive breast cancers, with a positive impact on the prognoses of affected patients.
Since it directly targets the biological action of the enzyme, trastuzumab is only effective for tumours that over express HER2, as measured by membrane staining across a 4-stage score system, ranging from 0 to 3+. Scores 0 and 1+ are considered inappropriate for trastuzumab treatment as the tumour is not over-expressing HER2, whereas 2+ and 3+ are candidates for treatment. This scale allows physicians to target therapies to the most suitable patients, who have the best chance of a positive response to the drug.
Biomarkers help us categorise and understand different groups of breast cancer patient. The role of ERBB2/HER2 in breast cancer is significant, but it is not universal for all patients. This makes biomarker testing crucial for the development of personalised treatment approaches, since HER2-positive breast cancers consistently respond differently to treatment compared to other subtypes.HER2 testing a cheap and effective way to achieve multiple clinical objectives: identifying likely patient outcomes, categorising subgroups according to malignancy, and targeting treatments to the most responsive patients.
Biomarker test kits work fast and can be used more freely than traditional methods such as biopsy which require surgery. As a method of identifying and categorising cancers, HER2 testing can detect certain chemical signatures of tumours more simply than imaging and biopsy, and critically also avoids the x-ray exposure of conventional imaging techniques. Identifying the HER2-expression status of a breast cancer patient is an essential clinical task, with early and frequent testing essential for the best possible outcome.
