HER2/neu protein
HER2/neu, or human epidermal growth factor receptor 2, is a protein that is part of the epidermal growth factor receptor family and is found on the surface of normal human cells. However, in certain cancers, notably breast cancer, HER2/neu can be overexpressed due to genetic alterations, leading to an increased number of these receptors on cell membranes. This overexpression contributes to more aggressive cancer behaviors, including rapid cell division and enhanced mobility, resulting in a poorer prognosis and decreased response to traditional chemotherapy.
Approximately 15 to 20 percent of breast cancers exhibit HER2/neu overexpression, making testing for this biomarker a routine part of diagnosis for invasive carcinoma. Targeted therapies, such as trastuzumab (Herceptin), have been developed specifically for HER2-positive cancers and have demonstrated improved survival rates when used in combination with chemotherapy. Other innovative treatments, including antibody-drug conjugates and specialized inhibitors, are also being explored to effectively target HER2-positive breast cancer.
Symptoms associated with breast cancer may include changes in breast shape or size, lumps, and other noticeable alterations in breast or nipple appearance. The understanding of HER2/neu's role in cancer has evolved significantly since its identification in the early 1980s, leading to advancements in both diagnostics and therapeutics aimed at improving patient outcomes.
On this Page
Subject Terms
HER2/neu protein
CATEGORY: Carcinogens and suspected carcinogens
ALSO KNOWN AS: Human epidermal growth factor receptor 2, ERBB2, ErbB2, HER-2, HER2
RELATED CANCER: Breast cancer
DEFINITION: HER2/neu (human epidermal growth factor receptor 2) is one of four members of the epidermal growth factor receptor family. It is a receptor that is present normally on the outer membranes of cells. Certain growth factors are responsible for the activation of these receptors, triggering them to send proliferation signals to the cell. However, HER2/neu is often overexpressed in various cancers such as breast cancer, typically because of a genetic alteration in the HER2/neu gene causing an increase in the number of HER2/neu receptors on the cell surface. Overexpression of the receptor causes cells to divide more rapidly and increases their mobility and invasion potential. HER2/neu overexpressing cells are more likely to form aggressive cancers.
Exposure routes: Overexpression is typically caused by a genetic alteration in the HER2/neu gene.
Where found: The protein is found in normal human cells, but overexpression is seen only in cancer cells.
At risk: HER2/neu overexpression occurs in about 15 to 20 percent of breast cancers.
Etiology and symptoms of associated cancers: HER2/neu-positive breast cancers are characteristically more aggressive, have poorer prognosis, and have poor chemotherapy response. Herceptin, a targeted treatment developed for HER2/neu-positive tumors, has been shown to increase survival rates when combined with chemotherapy. It can also significantly reduce the risk of recurrence in women with HER2/neu-positive tumors.
Symptoms of breast cancer include any change in the size or shape of the breast, change in the look or feel of the breast or nipple, or any lumps or thickening in or near the breast or underarm area. Other more obvious changes include nipple discharge, tenderness, inverted nipple, ridges, or pitting of the breast (when the skin looks like an orange).
History: Epidermal growth factor receptors were first identified as potential oncogenes in the early 1980s. Researchers have shown that a mutated form of the receptor links cell-growth signals to cancer. The discovery of similar oncogenes led to the identification of HER2/neu, which was quickly found to be overexpressed in breast cancer patients and correlated with metastatic and aggressive forms of the disease. Testing for HER2/neu overexpression is standard for any newly diagnosed invasive carcinoma. The tests used include fluorescence in situ hybridization (FISH) to measure the number of genes that code for HER2/neu and immunohistochemistry (IHC), which measures the amount of HER2/neu protein expressed on the surfaces of cancer cells.
Several advances have been made in the treatment of HER2/neu-positive breast cancer in the twenty-first century. Medical researchers developed antibody-drug conjugates (ADCs) designed to deliver cancer-fighting drugs directly to cancer cells through antibodies targeting HER2/neu. Targeted therapies, including trastuzumab deruxtecan, an ADC, and tucatinib, a small molecule tyrosine kinase inhibitor, have shown effectiveness in treating HER2-positive metastatic breast cancer. Combining novel and traditional therapies has also proven successful. The identification of biomarkers has also allowed doctors to determine better to which treatment HER2-positive breast cancer will best respond.
Bibliography
“Breast Cancer HER2 Status - What is HER2 Status?” American Cancer Society, 25 Aug. 2022, www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed 4 July 2024.
Buza, Natalia, Dana M. Roque, and Alessandro D. Santin. "HER2/neu in Endometrial Cancer: A Promising Therapeutic Target with Diagnostic Challenges." Archives of Pathology and Laboratory Medicine, vol. 138.3, 2014, pp. 343–50.
Chivukula, Mamatha. "Advances of HER2 Testing for Women with Breast Cancer." Translational Breast Cancer Research, vol. 4, 2023, doi.org/10.21037/tbcr-23-3. Accessed 4 July 2024.
Giridhar, Karthik. “HER2-positive Breast Cancer: What is it?” Mayo Clinic, 9 Apr. 2024, www.mayoclinic.org/diseases-conditions/breast-cancer/expert-answers/breast-cancer/faq-20058066. Accessed 4 July 2024.
“HER2 Status and HER2-Positive Breast Cancer.” Breastcancer.org, 30 Mar. 2024, www.breastcancer.org/pathology-report/her2-status. Accessed 4 July 2024.
Molina, Rafael, et al. "Circulating Levels of HER-2/neu Oncoprotein in Breast Cancer." Clinical Chemistry and Laboratory Medicine, vol. 50.1, 2012, pp. 5–21.
Seliger, Barbara, and Rolf Kiessling. "The Two Sides of HER2/neu: Immune Escape versus Surveillance." Trends in Molecular Medicine, vol. 19.11, 2013, pp. 677–84.
Swain, Sandra M., et al. "Targeting HER2-positive Breast Cancer: Advances and Future Directions." Nature Reviews Drug Discovery, vol. 22, no. 2, 2023, pp. 101-126, doi.org/10.1038/s41573-022-00579-0. Accessed 4 July 2024.