HER2, or Human Epidermal Growth Factor Receptor 2, is a protein found on the surface of all human cells, playing a role in normal cell growth and repair. In some cancers, cells can have too many copies of the HER2 gene, leading to an overproduction of the HER2 protein on their surface. This excess protein acts like an “on” switch, constantly signaling the cancer cells to grow, divide, and spread more rapidly than typical cells. Determining a cancer’s HER2 status involves assessing the amount of this protein or the number of HER2 gene copies present within the tumor cells. This classification provides oncologists with specific, actionable information, making it a foundational element in developing a patient’s individualized treatment plan.
Determining HER2 Status
Identifying a tumor’s HER2 status involves specialized laboratory tests performed on tissue samples, most commonly obtained through a biopsy or surgical removal. Immunohistochemistry (IHC) is one primary method that assesses the amount of HER2 protein on the surface of cancer cells. This test employs specific antibodies that bind to the HER2 protein, causing the cells to stain a particular color under a microscope. The intensity and completeness of this staining correlate with the amount of HER2 protein detected, allowing pathologists to score the results on a scale from 0 to 3+.
When an IHC test yields an ambiguous result (typically 2+), or when more definitive gene amplification assessment is needed, a Fluorescence In Situ Hybridization (FISH) test is often performed. FISH directly counts HER2 gene copies within cancer cell DNA using fluorescent probes. By determining the ratio of HER2 gene copies to a control gene, FISH provides a clear picture of gene amplification.
Understanding Test Results
The results from HER2 status tests categorize tumors into distinct groups, each carrying different implications for treatment selection and prognosis. A tumor is considered HER2-positive if it shows a high level of HER2 protein overexpression (typically an IHC score of 3+) or if it has an increased number of HER2 gene copies as determined by a positive FISH test. This indicates that the HER2 pathway is a significant driving force for the cancer’s uncontrolled growth and proliferation.
Conversely, a tumor is classified as HER2-negative if it exhibits little to no HER2 protein on its surface, corresponding to an IHC score of 0 or 1+. In these cases, the HER2 gene is not amplified, and the HER2 protein is not considered a primary driver of cancer growth. Standard chemotherapies or hormone therapies are often used for these tumors, as HER2-targeted drugs would not be effective.
An important category is HER2-low, for tumors with some detectable HER2 protein but not enough to be HER2-positive. This involves an IHC score of 1+ or an IHC score of 2+ with a negative FISH test. This distinction is relevant as it allows for specific, newer therapies targeting these lower HER2 levels.
Implications for Cancer Behavior and Prognosis
The HER2 status of a tumor significantly influences its biological characteristics and how it behaves within the body. HER2-positive cancers tend to be more aggressive, meaning they can grow and spread more rapidly throughout the body compared to tumors that lack this overexpression. This increased rate of proliferation and potential for metastasis historically contributed to a less favorable outlook for patients, as these tumors were harder to control with conventional treatments.
However, understanding HER2 as a driver of cancer growth has transformed this prognosis. While HER2-positive tumors remain biologically aggressive, specific targeted treatments have altered the disease trajectory. These therapies effectively counteract HER2 overexpression, leading to improved disease control and survival rates. What once indicated a challenging diagnosis now often points to effective treatment and improved long-term outcomes.
Targeted Treatment Approaches
Understanding a tumor’s HER2 status directly informs the selection of targeted therapies designed to counteract the overactive HER2 protein. These treatments interfere with HER2 signaling pathways, inhibiting cancer cells’ growth, division, and survival. This personalized approach has transformed the management of HER2-driven cancers.
One class of drugs includes monoclonal antibodies, such as trastuzumab and pertuzumab. These large protein molecules bind to HER2 receptors on the cancer cell surface. By binding, they block growth signals and mark cancer cells for destruction by the immune system. These antibodies can be administered alone or in combination.
Antibody-drug conjugates (ADCs) combine a HER2-targeting antibody with a chemotherapy drug, linked by a chemical bond. The antibody delivers the chemotherapy directly into HER2-expressing cancer cells, minimizing damage to healthy tissues. Trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (Enhertu) are examples, with trastuzumab deruxtecan effective even in HER2-low tumors.
Another class of targeted agents includes kinase inhibitors, small molecule drugs like lapatinib and neratinib. Unlike antibodies, these inhibitors penetrate the cell membrane to block HER2-activated signaling pathways inside the cell. By disrupting these internal signals, they prevent cancer cells from receiving continuous growth messages, expanding therapeutic options and sometimes overcoming resistance.