Exciting Findings for Metastatic Breast Cancer Patients
- A large majority of people are not aware that there are different types of breast cancer. Among them, there is a classification of the HER2 breast cancer subtype.
- To identify metastatic breast cancer patients with low HER2 expression (for whom Enhertu® may be considered as a targeted treatment) the PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody was approved.
- Enhertu is a specifically engineered HER2-directed antibody drug.
- You should ask your doctor if your disease is considered HER2-low. If it’s unknown, ask if you need another biopsy to determine the true nature of your breast cancer, and then ask if Enhertu is a drug you’re eligible to receive.
HER2 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.Read More
To understand how this precision medicine works, it’s important to look at how HER2 presents in the body.
“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 at Memorial Sloan Kettering Cancer Center, 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.
The new test to identify HER2 “low” cases
The 4B5 Rabbit Monoclonal Primary Antibody test can be used to standardize immunohistochemistry processes (immunohistochemistry analysis is a method for demonstrating the presence and location of proteins in tissue sections). By standardizing this processes, there is a decrease in human error in the laboratory setting.
This new test includes an algorithm that allows pathologists to score HER2 expression and identify the low expressers.
The PATHWAY anti-HER2 (4B5) test includes a scoring algorithm that helps pathologists to identify “low expressers” of HER2, assigning a HER2 low status to this group of patients. With this lower cutoff, the test is able to identify patients who may benefit from Enhertu as a treatment option, said Roche, the company behind its development.
“Roche is proud to lead the way in HER2 diagnostics through critical innovations that support the identification of patients who may benefit from novel HER2-targeted therapies,” said Thomas Schinecker, CEO of Roche Diagnostics. “Previously, metastatic breast cancer patients with a lower level of HER2 expression were considered to be part of the HER2-negative population and had no HER2-targeted treatment options. Now, they may be eligible for a HER2-targeted therapy, significantly increasing the number of patients who could have improved outcomes.”
What Is Enhertu?
Enhertu (chemical name trastuzumab deruxtecan) is not traditional chemotherapy, but is a unique type of medication termed an antibody-drug conjugate.
In this type of therapy, an antibody is linked to chemotherapy or another drug to provide a targeted approach to cancer treatment. The antibodies serve as the vehicle and the drug serves as the payload once the antibody reaches the cancer cell. The benefits of this type of therapy include decreased side effects and a more targeted approach compared to systemic chemotherapy.
Durexecan is the payload, or chemo, for Enhertu, and trastuzumab is the antibody.
In the setting of Enhertu, the drug is bound to an antibody that targets the HER2 receptor. Once the antibody reaches the cancer cell, it will interact with the HER2 receptor which causes a release of the payload. When the payload is released it diffuses a very short distance to kill the cancer cell without harming additional surrounding cells.
Enhertu for HER2-low patients
Enhertu had previously shown success in women with HER2-positive breast cancer, but validation in the newly defined HER2-“low” cohort hadn’t been established in a large study. What this means is that in patients who had HER2-positive tumors, the drug Enhertu had shown success, but it was unknown what would happen in patients with only minor HER2 expression — that being, the HER2-“low” group.
“One of the most challenging types of cancer to treat is metastatic breast cancer, which means breast cancer cells have spread from the breast to another part of the body like the liver or the bone. A new treatment, an FDA approved treatment, called Enhertu, is being used to improve the survival of patients with a new classification of metastatic breast cancer called HER2-low. So for anybody that’s watching, if they or their loved one has metastatic breast cancer, it’s critical that they ask their doctor: ‘do I have HER2-low metastatic breast cancer?'” said Dr. Comen.
The study on Enhertu in HER2-low patients was “groundbreaking,” according to the group of medical professionals. Results showed that women taking the drug had improvements in overall survival, despite having received multiple lines of prior treatment. This is not commonly seen in the metastatic setting; SurvivorNet’s physician experts tell us that these results should give hope to thousands of patients.
“The reason why it (the study) got so much attention is because of the improvement in overall survival, which is hard to do in metastatic breast cancer patients,” added Dr. Comen.
Metastatic Breast Cancer
Breast cancer is such a common cancer that many women have been touched by it in some way — either they’ve been diagnosed themselves, or they know someone who has been diagnosed.
Stage four breast cancer means that your cancer has now spread to distant areas of the body. It is no longer only in the breast area. And while there is no cure for metastatic breast cancer, doctors have a lot of options to treat this stage of advanced disease. One advantage to being such a common cancer is that breast cancer has been the focus of much research. What scientists have learned in the lab have translated into new and breakthrough treatments that are dramatically improving the outlook for people with this cancer. So if you have been diagnosed, you can be sure that your doctor will have a lot of options for treating you.
Questions to Ask Your Doctor
- Should I be tested for HER2 mutation?
- What will the treatment plan look like?
- What potential side effects should I be aware of?
- How can we weigh the risks vs. benefits of this new drug?