Human epidermal growth factor receptor 2, or HER2, is a protein on the surface of cells that helps regulate their growth. In some cancers, particularly breast cancer, a faulty gene can lead to an overabundance of this protein, a condition known as overexpression. This can cause cells to multiply uncontrollably and contribute to tumor formation. The quantity of HER2 protein on cancer cells influences the cancer’s behavior and the therapeutic strategies employed.
Understanding HER2 Test Results
To determine the amount of HER2 protein on cancer cells, a pathologist performs an immunohistochemistry (IHC) test. This process uses a special stain on a tumor tissue sample that contains antibodies that attach to HER2 proteins. The resulting color change reveals the protein quantity, which is graded on a scale from 0 to 3+.
A score of 0 indicates no HER2 proteins were detected, while a 3+ score signifies a large amount of HER2 protein, a condition called HER2-positive. A score of 2+ is considered borderline, meaning the result is uncertain and requires a follow-up test for clarification. A HER2 1+ result means a small number of HER2 proteins were found on the cells.
Historically, cancers with IHC 0 and 1+ scores were classified as HER2-negative. Because the cancer was not considered to be driven by the HER2 protein, targeted therapies were not offered to these patients. This traditional grouping shaped treatment decisions for many years.
The HER2-Low Classification
Recent advancements in oncology have introduced a new category known as “HER2-low.” This classification has changed how clinicians view cancers previously labeled as HER2-negative, as it recognizes that even a small amount of HER2 protein can be a target for specific therapies. This has been a shift in the landscape of breast cancer treatment.
Cancers are identified as HER2-low if they have an IHC test score of 1+. This category also includes tumors that score 2+ on the IHC test but are found to be negative on a subsequent, more definitive test called fluorescence in situ hybridization (FISH). The FISH test counts the number of HER2 genes inside the cancer cells, providing a clearer picture when the IHC result is ambiguous.
HER2-low is distinct from HER2-positive, which describes cancers with a high density of HER2 proteins (IHC 3+) that strongly drives their growth. In contrast, HER2-low cancers have a much smaller, but still detectable, amount of this protein. This distinction creates a separate diagnostic group with its own tailored treatment strategies.
Treatment Options for HER2-Low Cancer
The establishment of the HER2-low category has paved the way for a specialized class of drugs known as antibody-drug conjugates (ADCs). These therapies are engineered to work like a guided missile, specifically seeking out cancer cells that have HER2 proteins on their surface, even in low amounts. This targeted approach is an evolution from traditional chemotherapy.
The primary ADC used for HER2-low cancer is trastuzumab deruxtecan. This drug consists of a monoclonal antibody (trastuzumab) and a chemotherapy agent (deruxtecan). The antibody component is designed to find and attach to the HER2 proteins on the tumor cells. Once attached, the entire conjugate is taken inside the cancer cell.
Inside the cell, the ADC releases its chemotherapy payload directly, killing the cancer cell from within. This method allows a high concentration of the drug to be delivered to the tumor while minimizing exposure to healthy cells. This precision reduces some of the widespread side effects associated with standard chemotherapy.
Prognosis and Monitoring
The outlook for patients with HER2-low breast cancer has improved with the advent of targeted treatments. Antibody-drug conjugates have provided a therapeutic option for a group that previously had limited choices beyond standard chemotherapy. This ability to target low levels of HER2 protein has turned a negative result into a pathway for a potent treatment.
A HER2-low diagnosis means the cancer has a known biomarker that can be targeted, which has led to better outcomes. Patients with this diagnosis now have access to treatments that can more precisely attack their cancer.
Continuous communication with an oncology team is fundamental. Regular follow-up appointments are necessary to assess how the cancer is responding to treatment and to manage any side effects, ensuring the patient’s quality of life is maintained.