HER2 Classification for Breast Cancers
- 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.
- HER2 “low” may become a new commonly classified subtype of breast cancer.
- HER2 “low” as a breast cancer type would include approximately 50% of all patients and opens the door for new treatments and research.
- These patients may be eligible to receive life-changing treatment that they didn’t previously qualify for under their HER2-negative status, such as Enhertu
- In people with a specific subtype of breast cancer, Enhertu nearly doubled the time people lived without their cancer growing or spreading compared to chemotherapy
- Now, more patients are eligible to receive this promising therapy
“We’ve always done HER2 testing, but we’ve defined breast cancer as HER2-positive and negative. And now what we need to do is further redefine the negative given that it has treatment implications. So I think the key is education. So pathologists, oncologists, and patients know that negative is not negative.” – Dr. Aditya Bardia, Director of Translational Research Integration and Medical Oncologist at UCLA Health Jonsson Comprehensive Cancer Center, tells SurvivorNet.
Read MoreHER2 Breast Cancer: What does that mean?
HER2 is a protein that helps breast cancer cells grow quickly (HER2 is an acronym for Human Epidermal Growth Factor 2). Using proteins such as HER2 as a guide, researchers have been able to find new and exciting ways to treat breast cancer. “These receptors, I like to imagine them like little hands on the outside of the cell, they can grab hold of what we call ligands, and these ligands are essentially the hormones that may be circulating in the bloodstream that can then be pulled into this cancer cell and used as a fertilizer, as growth support for the cells,” Dr. Elizabeth Comen, a medical oncologist, told SurvivorNet in a previous conversation.Traditionally, the presence of HER2 has been divided into two groups, either positive or negative, leaving about 50% of patients somewhere in the middle. These groupings are based upon the way the tumors appear under a microscope when graded by the pathologist or with additional testing a pathologist may perform.
Understanding HER2 “low” breast cancer
Breast cancer cells with higher than normal levels of HER2 are called HER2-positive, and that corresponds to around 15%-20% of all breast tumors These cancers tend to grow and spread faster than breast cancers that are HER2-negative, but are much more likely to respond to treatment with drugs that target the HER2 protein, such as Enhertu.
Recently, however, researchers have looked to further expand this definition to include patients that have a minimal amount of HER2 expression but do not meet the classic definition for HER2-positive tumors. This group has been called HER2 “low” and is very important as it represents approximately 50 percent of all patients with breast cancer.
“What we’ve learned is that some of these patients we thought were HER2 negative are actually HER2 low, which means that in this trial, they actually responded to targeted medications called Enhertu, that targets the HER2 receptor, goes into the cancer cell, and kills it,” Dr. Comen adds.
Results from the DESTINY-Breast06 Trial
This FDA approval is based on a large clinical study called DESTINY-Breast06. In this trial, Enhertu was compared with standard chemotherapy in patients with hormone receptor (HR)-positive metastatic breast cancer that showed either HER2-low or HER2-ultralow levels.
So now it’s a broader label with Trastuzumab Deruxtecan. In general that is the preferred agent for any patient who’s a candidate for Trastuzumab Deruxtecan, given the magnitude of benefit we’ve seen with that drug. So usually we use Trastuzumab Deruxtecan first.” – says Dr Bardia
The findings were notable:
- Reduced Disease Progression Risk: Patients receiving trastuzumab deruxtecan had a 36% lower risk of their cancer worsening or leading to death compared with those who got chemotherapy.
- Longer Progression-Free Survival: Enhertu offered a median of 13.2 months without disease progression, whereas the chemotherapy group had about 8.1 months. In simpler terms, on average, Enhertu controlled the cancer for several more months than standard chemotherapy.
- Progression-free survival measures the amount of time that half of the people enrolled in the study were on treatment before their cancer started growing or spreading.
- Higher Response Rate: Over 60% of patients given Enhertu saw significant tumor shrinkage, compared with about 30% to 35% of patients who received chemotherapy.
- Response rate is the proportion of patients who have a partial or complete response to therapy
Who Is Eligible For Enhertu?
“It’s actually simpler now with the approval of trastuzumab deruxtecan for HER2-ultra-low. So if there’s any smidge that would meet the requirement as per the FDA label for trastuzumab deruxtecan, even 1% of HER2 staining, it qualifies for treatment. So it just simplifies things from an oncologist and patient perspective.” – adss Dr Bardia.
How Antibody-Drug Conjugate Work
Enhertu (also referred to as trastuzumab deruxtecan or T-DXd) an antibody-drug conjugate (ADC). In other words, it’s a targeted therapy designed to deliver a potent cancer-fighting medication directly into cancer cells that
“We call antibody drug conjugates, smart bombs or smart missiles. The idea is you have an antibody with chemo or payload attached to it.” – explains Dr Bardia.
“The antibody binds to a cancer cell and then selectively delivers the payload differentially to cancer cells. So it’s a way of selectively targeting or tagging the cancer cells and killing the cancer cells while sparing the normal cells.”
Potential Side Effects of Targeted Therapy
The negative effects of targeted therapy can be quite severe, so it’s important to inform your physician as soon as you experience any abnormal symptoms. Those who are taking more than one immunotherapy drug, referred to as combination therapy, are at an increased risk of experiencing side effects.
Common immunotherapy side effects include:
- Nausea/vomiting
- Decreased white blood cell count
- Anemia: decreased hemoglobin
- Fatigue
- Constipation
- Decreased appetite
There were several other potential side effects listed as well. Before beginning any new treatment, it’s important to discuss potential side effects with your doctor or medical team. To help manage the side effects, the healthcare provider may:
- Reduce the dose
- Delay the dose
- Or even stop the medication.
Questions to Ask Your Doctor
If you have questions about Enhertu or any aspect of your treatment plan, speak with your oncologist or a trusted member of your medical team.
Your healthcare professionals can help you weigh the benefits and risks of this new therapy and tailor a treatment approach that aligns with your overall goals and preferences.
- Should I be tested for HER2 mutation?
- What will the treatment plan look like?
- Am I eligible to receive Enhertu?
- Why do you think Enhertu is the right option for me at this point in my treatment?
- Is the safety and tolerability of Enhertu acceptable for long-term use?
- What potential side effects should I be aware of?
- How can we weigh the risks vs. benefits of this new drug?
Clinical Trials
Clinical trials are incredibly important both from an individual and a societal standpoint. These studies give patients, who have diseases that are not responding to typical treatments, access to a bevy of new drugs that are currently being developed by pharmaceutical companies.
Testing these treatments on people in experimental trials is really the best way for research to progress.
A lot of the therapies being tested in clinical trials will fail. However, participants in clinical trials are statistically more likely to have better outcomes, according to the Director of NYU Perlmutter Cancer Center, Dr. Ben Neel.
Among the large group of clinical trials that are currently underway, there will be some dramatic successes.
Dr. Ben Neel explains why he’d choose a clinical trial for himself.
SuvivorNet has a Clinical Trial Finder specifically designed to help patients navigate their options. You may see new results over the course of several days as new clinical trials are added daily.
You can also use clinicaltrials.gov, which is the national registry of trials, but it’s vast and a bit hard to navigate.
Consider asking:
- Is there any clinical trial on advanced metastatic breast cancer?
- Am I eligible for a clinical trial?
Learn more about SurvivorNet's rigorous medical review process.
