What is HER2-Low Breast Cancer? 

One of the ways of classifying breast cancers is by the level of a protein called HER2 on the surface of tumor cells. HER2, which stands for human epidermal growth factor receptor 2, helps control how breast cells grow, divide, and repair damage. 

Breast cancers marked by high levels of HER2 are known as HER2-positive and tend to grow and spread aggressively. Breast cancers with minimal levels of the protein are categorized as HER2-negative, and those with low levels are termed HER2-low. HER2-low tumors account for about 55% of all breast cancers, including some that are hormone receptor positive (meaning they grow in response to certain hormones) or triple-negative. 

Doctors use a procedure known as an IHC test to determine a breast cancer’s HER2 status: those with an IHC score of 3 or more are designated HER2-positive, and those with an IHC score of 0 and 1+ are HER2-negative. Patients with HER2-positive cancers may be treated with targeted therapies such as trastuzumab (Herceptin^®) that specifically target HER2 and can be very effective. 

Breast cancers with an IHC score of 2+ undergo a fluorescent in situ hybridization (FISH) test, which determines whether the tumor cells have extra copies of the gene for HER2. If they do, the cancer is HER-positive; if the FISH test is negative, the cancer is classified as HER2-low. 

It’s estimated that about 55% of all breast cancers fall into the HER2-low category, including some that are hormone receptor-positive.

How is HER2-low breast cancer treated? 

A clinical trial dubbed the DESTINY-Breast04 trial showed that patients with HER2-low breast cancer fared better when treated with trastuzumab deruxtecan, an agent that attaches chemotherapy to trastuzumab, compared to standard chemotherapy. The trial results, published in 2022, may benefit as many as 75% of all breast cancer patients — the 55% of those with HER2-low breast cancer and the 20% with HER2-positive cancer.

Care teams take a variety of factors into account to develop the best course of treatment for individual patients. 

Is HER2-low breast cancer a distinct subtype of breast cancer? 

A recent study led by Dana-Farber’s Sara Tolaney, MD, MPH, and Paolo Tarantino, MD, of Dana-Farber and the European Institute of Oncology, suggests that HER2-low is not a unique subtype of breast cancer. An analysis of data from more than 5,000 patients showed that these “HER2-low” tumors were no different — in their response to treatment and long-term outcomes — than “HER2-0” tumors, which lack the HER2 protein entirely or have only minuscule amounts of it.  

“Our findings show that the characteristics and behavior of HER-low and HER2-0 breast cancer do not differ significantly,” Tarantino says. “With further studies and the evolution of diagnostic technologies, we will hopefully see the benefit of novel anti-HER2 conjugates expand beyond HER2-low tumors to also reach patients with tumors currently defined as HER2-0.” 

About the Medical Reviewer

Dr. Tolaney received her undergraduate degree from Princeton University in 1998 and her medical degree from UC San Francisco in 2002. She subsequently completed her residency in Internal Medicine at Johns Hopkins University, and fellowships in hematology and medical oncology at Dana-Farber Cancer Institute. She obtained a Masters in Public Health from the Harvard School of Public Health in 2007. In 2008, she joined the staff of Dana-Farber Cancer Institute and Brigham and Women's Hospital, where she serves as Chief of the Division of Breast Oncology.  She is a breast medical oncologist whose research focuses on the development of novel therapies in the treatment of breast cancer.  She has been instrumental in developing several treatment approaches for breast cancer, including approaches focused on tailoring therapy for early stage HER2+ disease, use of cdk 4/6 inhibitors, antibody drug conjugates, and immunotherapy.