The human epidermal growth factor receptor 2 (HER2) is a protein on cell surfaces that influences cell growth and division. In some cancers, particularly breast cancer, increased HER2 protein can lead to uncontrolled cell growth. The introduction of “HER2-low” as a distinct category represents a significant advancement in cancer classification, broadening treatment options for many patients.
Understanding HER2 Status
HER2 status in cancer is determined by the amount of HER2 protein on tumor cells. Historically, classification was divided into HER2-positive and HER2-negative. HER2-positive cancers have high levels of the HER2 protein, promoting aggressive tumor growth and spread. These cancers account for approximately 15% to 20% of breast tumors and often respond to HER2-targeted therapies.
HER2-negative cancers were traditionally considered to have very low or no HER2 protein. The new “HER2-low” classification identifies a subset of cancers with low but detectable HER2 protein levels. This category includes many cancers previously classified as HER2-negative, encompassing about 45% to 55% of breast cancers. While primarily recognized in breast cancer, HER2-low is also being explored in other cancer types.
Diagnosing HER2-low Cancer
Determining HER2 status, including HER2-low, relies on analyzing tumor tissue samples. The most common method is immunohistochemistry (IHC). This test stains tumor tissue to quantify the HER2 protein on cancer cells.
IHC results are assigned a score from 0 to 3+. A score of 0 or 1+ indicates HER2-negative status, while 3+ signifies HER2-positive cancer. For a score of 2+, fluorescence in situ hybridization (FISH) is performed to check for extra copies of the HER2 gene. If the FISH test is negative (no gene amplification), and the IHC score is 1+ or 2+, the cancer is classified as HER2-low. This system allows for precise identification, guiding treatment decisions.
Treatment Approaches for HER2-low Cancer
The emergence of the HER2-low classification has expanded treatment possibilities for many patients, especially those with metastatic breast cancer where the disease has spread. Previously, these patients often had limited targeted treatment options if their cancer was not HER2-positive.
A major breakthrough for HER2-low cancers has been antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (Enhertu). These therapies combine a targeted antibody with a chemotherapy drug. The antibody binds specifically to the HER2 protein on cancer cells, even at low levels. Once attached, the ADC delivers chemotherapy directly into the cancer cell, minimizing damage to healthy cells. This approach allows for more focused and potent delivery compared to traditional chemotherapy, which affects all rapidly dividing cells.
Clinical trials, such as DESTINY-Breast04, have demonstrated benefits for patients with HER2-low metastatic breast cancer treated with trastuzumab deruxtecan. These studies showed improved progression-free and overall survival compared to standard chemotherapy. This success led to the approval of trastuzumab deruxtecan for HER2-low metastatic breast cancer, offering a new and effective option for patients who previously had fewer targeted therapies. The impact of this classification is significant for patients whose cancers were previously HER2-negative, including those with hormone receptor-positive or triple-negative subtypes.
Future Outlook in HER2-low Research
The understanding and treatment of HER2-low cancers continue to evolve. Researchers are investigating the potential for HER2-low classification to impact treatment strategies in other cancer types beyond breast cancer. This includes exploring whether similar ADCs or other targeted therapies could be effective for HER2-low expressions in different tumor types.
Ongoing research also focuses on refining diagnostic criteria for HER2-low to ensure consistent and accurate identification. The exploration of new targeted therapies and refinement of existing ones are important areas of study, aiming to further improve patient outcomes. This field holds promise for expanding personalized treatment approaches for a broader range of cancers.