Understanding how HER2-positive breast cancer is diagnosed can help you navigate the testing process with confidence and clarity. This type of breast cancer requires specific laboratory tests to identify the presence of excess HER2 protein, and knowing your HER2 status is essential for determining the most effective treatment approach.

Introduction: Who Should Undergo HER2 Testing

If you have been diagnosed with breast cancer, your healthcare provider will recommend testing to determine your cancer’s unique characteristics. HER2 testing is a standard part of this diagnostic process. Medical experts strongly advise that every person with invasive breast cancer should be tested for HER2 status, as this information significantly impacts which treatments will work best for you.^[1]

Testing is particularly important because HER2-positive breast cancer behaves differently from other types of breast cancer. In this form of cancer, cells produce too much of a protein called human epidermal growth factor receptor 2, or HER2, which causes cancer cells to grow and multiply more rapidly than normal.^[2] Around 15 to 20 percent of all breast cancers are HER2-positive, meaning they have high levels of this protein on the surface of their cells.^[3]

You should seek HER2 testing whenever breast cancer is first diagnosed. Testing determines not just whether you have HER2-positive disease, but also helps your medical team understand how aggressive your cancer may be and which targeted therapies might help. If your breast cancer returns or spreads to other parts of your body after initial treatment, your doctor will recommend retesting, as your cancer’s characteristics can sometimes change over time.^[1]

Testing should happen as soon as possible after a breast cancer diagnosis is confirmed through biopsy. Early identification of HER2 status allows your healthcare team to create a treatment plan tailored to your specific cancer type, which can improve outcomes and help you avoid unnecessary treatments that wouldn’t be effective for HER2-positive disease.^[8]

Classic Diagnostic Methods for Identifying HER2-Positive Breast Cancer

Diagnosing HER2-positive breast cancer requires tissue from your breast to be examined in a laboratory. The journey to understanding your HER2 status begins with a breast biopsy, a procedure where a small sample of breast tissue is removed for testing. If the biopsy confirms cancer is present, a specialist called a pathologist will examine the tissue cells specifically looking for signs of HER2 proteins.^[2]

The biopsy provides the actual tissue needed for testing, but determining HER2 status requires specialized laboratory methods. Two main types of tests are used to measure HER2 levels in your cancer cells. Each approach looks at HER2 from a slightly different angle, and sometimes both tests are needed to get a complete picture of your HER2 status.^[4]

Immunohistochemistry (IHC) Testing

The first commonly used test is called immunohistochemistry, or IHC for short. This test measures how much HER2 protein is present on the surface of your breast cancer cells. Laboratory technicians apply special stains to your tissue sample that attach to HER2 proteins, making them visible under a microscope. The pathologist then examines the stained tissue and assigns a score from 0 to 3+ based on how many HER2 proteins they observe.^[5]

A score of 0 or 1+ means the cancer is HER2-negative, with little to no extra HER2 protein detected. A score of 3+ indicates HER2-positive breast cancer, meaning there are high levels of HER2 protein present. If your test comes back with a score of 2+, the result is considered uncertain or borderline. In this case, your doctor will order an additional test to get a clearer answer about your HER2 status.^[5]

Fluorescence In Situ Hybridization (FISH) Testing

When IHC results are unclear, or to confirm a diagnosis, doctors use a test called fluorescence in situ hybridization, or FISH. Unlike IHC, which measures protein levels, FISH looks directly at the genes inside your cancer cells. It determines whether the HER2 gene has made too many copies of itself, a process called gene amplification.^[4]

During FISH testing, laboratory staff use fluorescent probes that attach to the HER2 genes in your tissue sample. Under a special microscope, these probes light up, allowing technicians to count how many HER2 genes are present in each cell. If there are extra copies of the HER2 gene beyond what’s normal, the test is positive, confirming HER2-positive breast cancer. This test is often considered more precise than IHC alone and can provide definitive answers in borderline cases.^[8]

Understanding Test Results and What They Mean

Your test results will classify your breast cancer as either HER2-positive or HER2-negative. Recently, doctors have also begun identifying a category called HER2-low, which refers to cancers that have some HER2 protein present but not enough to be considered HER2-positive. HER2-low cancers score 1+ on IHC testing, or 2+ on IHC with a negative FISH test.^[4]

All these tests also check for other important markers at the same time, including estrogen receptors and progesterone receptors. These are proteins that respond to hormones in your body. Your breast cancer might be HER2-positive and also positive for hormone receptors, sometimes called “triple-positive,” or it might be HER2-positive but negative for hormone receptors. Understanding all these markers together helps your doctor choose the right combination of treatments for your specific cancer.^[5]

The testing process typically takes several days to complete after your biopsy is performed. Your healthcare team will explain your results and what they mean for your treatment options. If you have concerns about your test results or don’t understand something, ask your doctor to explain further. These test results are crucial information that will guide every treatment decision moving forward.^[2]

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or new ways of using existing treatments for breast cancer. If you’re considering participating in a clinical trial for HER2-positive breast cancer, you’ll need to undergo specific diagnostic tests to determine whether you meet the study’s requirements. These tests help researchers ensure that participants have the exact type and stage of cancer the trial is designed to study.^[2]

The first and most important requirement for enrolling in a HER2-positive breast cancer trial is confirming your HER2 status through the standard IHC or FISH testing described earlier. Clinical trials typically require very precise documentation of your HER2 test results, including the specific score from IHC testing or the gene amplification ratio from FISH testing. Some trials may even require that your tissue samples be retested at a central laboratory to ensure consistency across all participants.^[8]

Beyond HER2 testing, clinical trials often require information about your cancer’s stage and whether it has spread beyond your breast. This may involve imaging tests such as mammograms, ultrasounds, CT scans, or MRI scans to see the size and location of your tumor and check whether cancer has reached your lymph nodes or other organs. Blood tests are also commonly required to check your overall health, including how well your liver and kidneys are functioning, and to measure your blood cell counts.^[2]

Some clinical trials studying treatments for HER2-positive breast cancer may require testing your heart function before you can participate. This is because some HER2-targeted therapies can affect the heart. Tests like an echocardiogram or a MUGA scan measure how well your heart is pumping blood and help doctors determine if it’s safe for you to receive certain treatments. Your heart will often be monitored throughout the trial with repeated testing to ensure it remains healthy.^[11]

Clinical trials may also require documentation of any previous breast cancer treatments you’ve received, including surgery, chemotherapy, radiation therapy, or targeted therapies. Researchers need to know your complete treatment history to understand how new treatments might work alongside or after previous therapies. You may need to provide medical records or pathology reports from past treatments.^[5]

If your cancer has spread to other parts of your body, additional biopsies may be needed to confirm that the metastatic tumors are also HER2-positive. Sometimes breast cancer changes its characteristics as it spreads, which is why retesting is important for clinical trial enrollment. The trial may require fresh tissue samples rather than relying solely on tests done when you were first diagnosed.^[1]

Genetic testing might also be part of the qualification process for certain clinical trials. While standard HER2 testing looks at HER2 protein levels or gene copies, some trials are exploring how other genetic factors influence how well HER2-positive cancers respond to treatment. You might be asked to provide blood or tissue samples for more extensive genetic analysis to see if you carry specific mutations that make you eligible for the study.^[2]