Breast cancer isn’t a single disease. Rather, it can be classified into several subtypes according to the molecular characteristics of a person’s tumor.
Stay empowered with the latest news, insights, and resources delivered to your inbox.
Important markers doctors look for when determining a patient’s breast cancer subtype are the human epidermal growth factor 2 (HER2) protein and estrogen and progesterone receptors (ER and PR). The presence or absence of HER2, ER, and PR helps doctors understand a tumor’s aggressiveness—and determine the right treatment plan for a patient.
What is HER2, and why is knowing your HER2 status so important? Learn the answers to these questions and more below.
HER2 is a protein found on the surface of all breast cells that directs their growth and repair, ensuring that the cells divide to replace those that are damaged or dying. But if the gene that makes HER2 proteins mutates and malfunctions, it instructs breast cells to keep growing; this uncontrollable growth leads to tumor formation. This subtype of breast cancer, called HER2-positive breast cancer, occurs when the HER2 gene produces too many copies of itself (gene amplification), creates too many copies of HER2 receptors (overexpression), or both.
Mentioned in this article:
About 15 to 20 percent of breast cancer patients have HER2-positive breast cancer. It is an invasive form of the disease that grows rapidly and is more likely to spread beyond the breast compared to other breast cancer subtypes. But when caught early, HER2-positive breast cancer can be successfully treated. In fact, our progress in treating HER2-positive breast cancer is seen as a crowning achievement, made possible because of research.
When you undergoHER2 testing, your doctor removes a sample of breast cancer cells via breast biopsy, which a pathologist then examines under a microscope to check for the presence of the HER2 protein. Identifying your HER2 status provides your doctor with crucial information about which types of treatments are most likely to be effective.
Due to its aggressive nature, HER2-positive breast cancer was once associated with a poor prognosis compared to other types of breast cancer. But that has changed with the development of treatments that target HER2 proteins on breast cancer cells, destroying the cells or slowing their growth. Thanks to research, the first targeted therapy for HER2-positive breast cancer, trastuzumab (Herceptin®), was approved in the late 1990s. Now, there are multiple therapies that specifically target HER2 on cancer cells, killing them with less harm to healthy cells. These strides in treatment have produced significantly improved survival outcomes, even in those with metastatic HER2-positive breast cancer.
Types of treatment for HER2-positive cancer include:
Targeted therapies are usually just one part of a person’s treatment plan. Standard therapies, such as chemotherapy or surgery, may also be included. Patients with early-stage HER2-positive breast cancer often get neoadjuvant chemotherapy—neoadjuvant referring to a treatment given prior to surgery—followed by adjuvant (post-surgery) HER2-targeted therapy. And a combination of chemotherapy and the monoclonal antibodies trastuzumab and pertuzumab is the standard first-line treatment for most patients with advanced HER2-positive breast cancer.
Breast biopsy samples can undergo two tests to determine HER2 status: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
IHC detects the number of HER2 receptors on the surface of breast cancer cells. A pathologist uses a chemical dye that attaches to HER2 proteins—a process called immunostaining—and assigns a value (0 to 3+) based on the amount of dye present. A score of 0 to 1+ is typically classified as negative, while results that show a moderate amount of HER2 (2+) are considered borderline and will need a FISH test to confirm if HER2 is positive or negative. A score of 3+ is considered positive.
The HER2 FISH test measures the number of copies of the HER2 gene in breast cancer cells. It’s more sensitive than IHC but is not as widely available. In FISH testing, pathologists use a fluorescent marker that binds to HER2 proteins, allowing them to detect HER2 presence using a fluorescence microscope. Tumors that are 2+ by IHC are then tested by FISH – those that are FISH+ are then called HER2-positive and those that are FISH- are called HER2-negative.
Your pathology report will show your HER2 status as either HER2-positive or HER2-negative. This status helps doctors determine whether you’ll benefit from HER2-targeted treatments.
Here’s how these two categories are scored:
HER2-positive: In HER2-positive breast cancer, the cancer cells make a lot of HER2 protein. If the IHC is 3+, or it is 2+ and the FISH is positive, it’s considered HER2-positive and can be treated with any HER2-targeted therapy.
HER2–negative: If IHC is 0 with no staining, a patient has HER2-negative breast cancer. This means the cancer cells have a normal amount of HER2 proteins, so targeted HER2 therapies will not be effective. To determine the best course of treatment, doctors will look at other factors, including hormone receptor status.
You may have also read about two emerging “in between” HER2 statuses: HER2-low and HER2-ultralow. At this time, these classifications only have implications for patients with metastatic breast cancer, and they’re not part of a routine pathology report.
Previously, any IHC score below 3 was considered HER2-negative. But over just the past few years, a newer treatment—the antibody-drug conjugate trastuzumab deruxtecan (Enhertu®)—was shown to target lower levels of HER2 than previously thought possible, leading to these emerging classifications. Right now, BCRF researchers and others are refining what, precisely, classifies breast cancers as HER2-low and -ultralow and devising tests that are more sensitive than IHC and FISH.
Here’s how HER2-low and -ultralow are currently scored (for metastatic breast cancer patients only):
HER2-low: HER2-low is an emerging classification that means a tumor has low levels of HER2 proteins (the IHC is 1+ or if the IHC is 2+ but the FISH is negative). While HER2-low breast cancer doesn’t tend to respond to widely-used HER2-targeted therapies, it may respond to the antibody-drug conjugate trastuzumab deruxtecan (Enhertu®).
HER2-ultralow: Another emerging classification, HER2-ultralow means that breast cancer cells contain even fewer HER2 proteins than HER2-low breast cancer cells—if the IHC score is 0 with staining (HER2+ staining in more than 0 percent but no more than 10 percent of tumor cells). Like HER2-low cancers, HER2-ultralow cancers may respond to the antibody-drug conjugate trastuzumab deruxtecan (Enhertu®).
BCRF supports numerous investigators focused on HER2-related breast cancers. From developing new treatments for HER2-positive breast cancer to refining HER2 status testing, BCRF investigators are at the forefront of research to improve outcomes for people diagnosed with this subtype.
Read more about BCRF-supported research in our guide to HER2-positive breast cancer.
Breast Cancer HER2 Status | What is HER2 Status? (n.d.). American Cancer Society. https://www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html
HER2-Positive breast cancer. (2025, February 7). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/25213-her2-positive-breast-cancer
Targeted Drug therapy | Breast cancer treatment. (n.d.). American Cancer Society. https://www.cancer.org/cancer/types/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html
Swain, S. M., Shastry, M., & Hamilton, E. (2022). Targeting HER2-positive breast cancer: advances and future directions. Nature Reviews Drug Discovery, 22(2), 101–126. https://doi.org/10.1038/s41573-022-00579-0
Noble, Dana. (2024, December 5). HER2-positive breast cancer treatments. Mayo Clinic Press. https://mcpress.mayoclinic.org/cancer/her2-positive-breast-cancer-treatments/
Gogia, P., Ashraf, H., Bhasin, S., & Xu, Y. (2023). Antibody–Drug Conjugates: A review of approved drugs and their clinical level of evidence. Cancers, 15(15), 3886. https://doi.org/10.3390/cancers15153886
Treatment options for HER2-Positive breast cancer. (n.d.). WebMD. https://www.webmd.com/breast-cancer/her2-positive-treatments
Martínez-Sáez, O., & Prat, A. (2021). Current and future management of HER2-Positive metastatic breast Cancer. JCO Oncology Practice, 17(10), 594–604. https://doi.org/10.1200/op.21.00172
Adams, M. (2022, September 9). What is HER2 low breast cancer? MD Anderson Cancer Center. https://www.mdanderson.org/cancerwise/her2-low-breast-cancer-expert–precise-diagnosis-can-lead-to-personalized-treatment.h00-159542901.html
Silver, N. (2024, May 20). What’s the difference between HER2-Negative and HER2-Positive breast cancer? Healthline. https://www.healthline.com/health/breast-cancer/her2-positive-vs-her2-negative#her-2-status-and-treatments
Noble, Dana. (2025, February 6). HER2-low breast cancer: What to expect. Mayo Clinic Press. https://mcpress.mayoclinic.org/cancer/her2-low-breast-cancer-what-to-expect/
Information and articles in BCRF’s “About Breast Cancer” resources section are for educational purposes only and are not intended as medical advice. Content in this section should never replace conversations with your medical team about your personal risk, diagnosis, treatment, and prognosis. Always speak to your doctor about your individual situation.
BCRF’s “About Breast Cancer” resources and articles are developed and produced by a team of experts. Chief Scientific Officer Dorraya El-Ashry, PhD provides scientific and medical review. Scientific Program Managers Priya Malhotra, PhD, Marisa Rubio, PhD, and Diana Schlamadinger, PhD research and write content with some additional support. Director of Content Elizabeth Sile serves as editor.
Support research with a legacy gift. Sample, non-binding bequest language:
I give to the Breast Cancer Research Foundation, located in New York, NY, federal tax identification number 13-3727250, ________% of my total estate (or $_____).
Stay in the know with the latest research news, insights, and resources delivered to your inbox.
Follow BCRF on all the major platforms for research news, inspiring stories, and more.