Are Patients Being Reclassified as HER2-Low?
- Breast cancer patients designated as HER2-negative should be asking their doctors if they are really HER2-low.
- HER2 is a protein found on the surface of breast cancer cells, and a patient’s level (positive or negative) helped define their treatment options.
- However, tumors classified as HER2-negative may still have a minimal amount of HER2 expression, leading to the emergence of a new classification called HER2-low.
- These patients may be eligible to receive life-changing treatment that they didn’t previously qualify for under their HER2-negative status.
- Targeted drugs like Enhertu show significant effectiveness and can extend overall survival rates.
- The experts we talked to at major cancer centers said they are indeed seeing patients be reclassified and getting Enhertu.
- Awareness and proactive efforts from patients and oncologists are needed to ensure patients are getting the reclassification they need.
But on the ground, are women actually being reclassified, and is new treatment actually getting to these new patients?Read More
"Yes absolutely. With over 60% of patients being HER2-low, this is opening up a lot of treatment options for many patients,” she added.
What Is HER2 in Breast Cancer?
HER2 is the human epidermal growth factor receptor 2 protein that can be found on the surface of most breast cancer cells. However, the levels of this protein can vary significantly from one patient to another.
Understanding a patient’s HER2 level can help doctors determine the best course of treatment.
Tests like immunohistochemistry (IHC) can be used to measure these levels.
IHC utilizes numeric scores to indicate the degree of HER2 expression. A score of 0 indicates no expression of the protein (HER2-negative), while the highest score of +3 represents maximal expression.
Breast cancer cells with higher than normal levels of HER2 are called HER2-positive, found in 15-20% or all breast tumors. While they tend to grow faster, they are much more likely to respond to treatment with drugs that target the HER2 protein.
However, tumors previously classified as HER2-negative were found to still have a minimal amount of HER2 expression, leading to the new grouping of HER2-low.
It turns out, 50-60% of all breast cancers are classified as HER2-low.
"What we've learned is that some of these patients we thought were HER2-negative are actually HER2-low,” Dr. Elizabeth Comen previously told SurvivorNet.
She added that earlier studies revealed that “they actually responded to targeted medications that target the HER2 receptor goes into the cancer cell, and kills it," Dr. Comen adds.
While this group didn't meet the requirements for older drugs that treated HER2-positive cancer, newer and more potent drugs they didn't previously qualify for (like Enhertu, or trastuzumab deruxtecan) are now offering life-changing benefits.
Enhertu was approved in 2022 and can extend overall survival rates. It’s approved for people with HER2-low breast cancer that is stage 4 (metastatic) or unable to be removed with surgery.
“The impressive anti-tumor efficacy has broadened treatment options for many patients, leading to meaningful clinical responses in individuals living with advanced breast cancer and improved their quality of life,” Dr. Lustberg added.
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Do Patients Need Additional Biopsies To See If They Are HER2-Low?
Most patients do not require new biopsies to determine their HER2-low status, which can be helpful for the patient.
“You can examine the original breast cancer tissue that has been stored in the pathology lab and test it for HER2,” Dr. Julie Gralow, the Chief Medical Officer and the Executive Vice President of ASCO, told SurvivorNet at the height of the HER2-low buzz.
However, caution is advised when using such tissue because the HER2 expression in tumors can change over time. This is particularly relevant for patients initially classified as HER2-negative, as they may need a new biopsy of one of their metastatic sites to reassess their receptor status.
When selecting a new biopsy site, it is wise to choose a location that can provide sufficient cancer tissue for reliable testing, such as a lymph node rather than a bony metastatic focus.
Dr. Nancy Lin, medical oncologist at Dana-Farber Cancer Institute and Susan G. Komen scholar, summarizes whether patients need new biopsies or not, saying "In many cases, this just requires going back to the original pathology reports; in other cases, repeat HER2 immunohistochemistry testing (IHC testing) is ordered on old biopsy/tissue samples, and in some cases, a new biopsy is performed to determine the current HER2 status of the tumor."
HER2-Low Classification & Treatment For Breast Cancers
New medications such as Enhertu (trastuzumab deruxtecan), can now be used for metastatic HER2-low cancers.
"This drug has been around for a few years, and it's very effective in the HER2-positive population," Dr. Gralowpreviously told SurvivorNet.
She continued, "Now, however, we have a whole, huge group of [HER2 low] patients who have the potential for benefit, who we never even thought of giving HER2 targeted therapy to."
Dr. Lustberg echoed this sentiment, "The approval of trastuzumab in the treatment of patients with unresectable or metastatic HER2-low breast cancer is an important advance for patients living with advanced breast cancer."
She continues, "The new classification means that around 60% of patients that were historically HER2-negative are now recategorized as HER2-low. This provides a large population of patients the opportunity to receive targeted therapy with [significant benefits} over previously used chemotherapy agents."
“I can’t tell you the impact this has had,” Dr. Eleonora Teplinsky, head of Breast Medical Oncology at Valley Health System and clinical associate professor of medicine at The Icahn School of Medicine at Mount Sinai, told SurvivorNet.
“I have patients who were not responding to lines and lines of treatment that have had a wonderful year,” she added. “I think this really has changed the treatment of metastatic breast cancer in a positive way.”
Dr. Teplinsky added that of all the ASCO conferences she’s attended, this new classification of HER2-low breast cancers was “by far on the top five” of developments that changed how doctors treat patients.
The promise of the HER2-low designation and the expansion of effective treatment options for patients were, therefore, very exciting.
"We now test all of our metastatic patients for HER2-low expression and use this new drug in a huge number of patients," Dr. Amy Tiersten, Professor of Hematology and Medical Oncology at the Dubin Breast Center at the Tisch Cancer Center at Mount Sinai, told SurvivorNet.
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What Can Breast Cancer Patients Do?
First, reaping the full reward of this new classification may require proactive effort from the patients themselves.
Those who were initially classified as HER2-negative should consult with their oncologists to see if they are HER2-low instead.
“Every patient with breast cancer will want to know if they are HER2-low,” Dr. Allison Zibelli, MD, FACP Vice-Chair, Oncology and Assistant Professor of Medicine at the Sidney Kimmel Cancer Center at Thomas Jefferson University, previously told SurvivorNet.
Questions to Ask Your Doctor
Here are some questions you may consider asking your doctor to get the conversation started:
- Is my breast cancer actually HER2-low? Can I be retested?
- Is my old biopsy enough to determine if I should be reclassified?
- Do I need a new biopsy to determine the HER2 status of my breast cancer?
- If my cancer is HER2-low, am I eligible for targeted therapies like Enhertu?
- What are the benefits of such therapies? What are their risks?
What Can Doctors Do?
Oncologists should also make a concerted effort to retest their metastatic breast cancer patients to see if they are in fact HER2-low, despite being labeled negative on their initial biopsies.
This applies to patients not receiving any treatment or those receiving traditional chemotherapies. Such patients may find that they are instead eligible for HER2-low targeted therapies, like Enhertu, which may improve their quality of life and help them live longer.
"Patients who received Enhertu experienced a higher chance of tumor shrinkage, longer length of disease control, and longer survival," says Dr. Lin.
As more people – both patients and oncologists, including those in the community setting – become aware of the importance of knowing whether their HER2 status is low instead of negative, we will likely see more and more people being eligible for and receiving the full benefits of HER2-low targeted therapies.