Human Epidermal growth factor Receptor 2, known as HER2, is a gene that produces proteins found on cell surfaces. These HER2 proteins normally function as receptors, regulating cell growth, division, and repair. In cancer, “overexpression” means a genetic change causes a cell to produce an excessive number of HER2 proteins. This overabundance on the cell surface can significantly influence the behavior of certain cancers.
The Role of HER2 in Cell Growth
Think of HER2 receptors on a cell’s surface like an accelerator pedal for cell growth. In a healthy cell, the body carefully controls the number of these receptors and when they are “switched on” to ensure balanced growth and division. This regulation prevents uncontrolled proliferation, maintaining normal tissue function.
When HER2 is overexpressed, cancer cells have far too many of these accelerator pedals on their surface. These excess receptors are constantly stimulated, receiving excessive growth signals. This continuous signaling drives uncontrolled cancer cell growth and division, contributing to tumor development. This overexpression is usually a somatic mutation, arising within cancer cells during a person’s lifetime, rather than being inherited.
Diagnosing HER2 Status
Determining a tumor’s HER2 status involves testing a sample of tumor tissue, usually obtained through a biopsy or surgery. This testing helps doctors understand cancer cell characteristics. Results guide treatment decisions, as HER2-positive cancers often respond to specific targeted therapies.
Two primary tests assess HER2 status. Immunohistochemistry (IHC) is often the first test, using special stains to measure the amount of HER2 protein on the surface of cancer cells. IHC results are reported on a scale from 0 to 3+, where 0 and 1+ indicate HER2-negative status, and 3+ indicates HER2-positive status. Tumors scoring 3+ show strong, complete membrane staining in over 10% of tumor cells, indicating high HER2 protein levels.
If an IHC result is 2+, it is considered “equivocal” or borderline, meaning HER2 status is uncertain. In such cases, a second test, Fluorescence In Situ Hybridization (FISH), is performed for a definitive answer. FISH directly counts the number of copies of the HER2 gene inside cancer cells. A FISH test is considered positive if the ratio of HER2 gene copies to a control gene is 2.0 or greater, confirming HER2-positive status.
A newer classification, “HER2-low,” applies to tumors with some HER2 protein expression but not enough to be considered HER2-positive. This includes tumors with an IHC score of 1+ or those with an IHC score of 2+ but a negative FISH result. This distinction is becoming increasingly relevant as new treatment options are being developed for this subset of cancers.
Cancers Associated with HER2 Overexpression
HER2 overexpression is most common in breast cancer, affecting 15% to 20% of cases. HER2-positive breast cancers tend to grow and spread more quickly than HER2-negative types. However, HER2 presence makes them susceptible to targeted therapies, which has significantly improved patient outcomes.
Beyond breast cancer, HER2 status is routinely assessed in other cancers to guide treatment decisions. This includes gastric (stomach) cancer and gastroesophageal junction adenocarcinoma, where HER2 overexpression is found in 10% to 30% of cases. HER2 overexpression can also be observed less frequently in other cancers, such as esophageal, bladder, ovarian, endometrial, lung, and colorectal cancers. For advanced disease, HER2 testing may be considered to explore potential targeted treatment options.
Targeted Treatment Approaches
Targeted therapy focuses on specific molecular features of cancer cells, such as the HER2 protein, while minimizing harm to healthy cells. These treatments exploit vulnerabilities created by HER2 overexpression, offering a more precise approach than traditional chemotherapy. Their development has reshaped the treatment landscape for HER2-positive cancers.
One class of HER2-targeted drugs includes monoclonal antibodies, such as trastuzumab and pertuzumab. These laboratory-made proteins attach to the extracellular part of HER2 receptors on the cancer cell surface. By binding to HER2, they block receptors from receiving growth signals, effectively “locking” the accelerator pedal and preventing uncontrolled cancer cell growth and division. Trastuzumab, for example, also helps the immune system recognize and attack cancer cells.
Another class is Antibody-Drug Conjugates (ADCs), like ado-trastuzumab emtansine and fam-trastuzumab deruxtecan. Often described as “smart bombs,” ADCs combine a monoclonal antibody with a potent chemotherapy drug. The antibody acts as a homing device, recognizing and binding to HER2-positive cancer cells. Once attached, the ADC delivers the chemotherapy payload directly into the cancer cell, maximizing its destructive effect on the tumor while limiting damage to healthy tissues.
Prognosis and Patient Outlook
Historically, HER2-positive cancer was associated with a more aggressive course and a less favorable prognosis. These tumors were known for rapid growth and higher likelihood of spreading. However, HER2-positive cancer treatment has transformed with the advent of targeted therapies.
With HER2-targeted treatments, the outlook for patients has dramatically improved. HER2-positive status is now a treatable target, providing clinicians with a specific vulnerability to exploit. Early-stage HER2-positive breast cancer, treated with chemotherapy and dual antibody therapy, can have survival rates exceeding 90%. Even for metastatic disease, targeted therapies have significantly extended survival.
This shift means HER2-positive cancer, once considered aggressive, is now often more manageable, with outcomes comparable to or even better than some other cancer subtypes. The precise nature of the HER2 target allows for specialized, highly effective treatment options, fundamentally changing the patient journey and offering renewed hope.