Understanding HER2 as a tumor-agnostic biomarker in cancer care and what it means for treatment
In our recent “Ask the Expert” webinar with Dr. Heidi Ko, we examined the tumor-agnostic biomarker HER2 (human epidermal growth factor receptor 2) and the role it plays in cancer care. What does tumor-agnostic mean and what’s the significance of HER2?
Keep reading for Dr. Ko’s insights, transcribed from the discussion. Our full webinar recording is available if you’d like to listen to the full conversation.
The following questions and responses have been lightly edited for grammatical purposes.
1) What does the term “tumor-agnostic” in cancer care mean?
Tumor-agnostic therapy means that cancer treatment is based on the biology or unique molecular features of the tumor. It’s about the tumor’s “personality,” not exactly where the cancer started in the body. Most cancer treatments were actually developed for a specific type of cancer, like breast or colon cancer, but if a tumor has certain changes in its DNA or protein (specific mutations or alterations), we may be able to use a treatment that works for any cancer with that same change, no matter where the cancer started. That’s what we mean by tumor-agnostic. It doesn’t matter what kind of cancer it is or where it started in the body, just that it has that specific molecular feature.
A good analogy for this would be weeds growing in different gardens. I use weeds as an example because that’s something I deal with daily, living in San Antonio, Texas. In this analogy, the gardens might be the lung, colon, or breast. The weeds have the same root system, no matter where they grow, in the backyard, front yard, or any other garden.
A tumor-agnostic biomarker is like spotting that root system. If we find it, we can use a treatment that targets the root, regardless of which garden the weeds are in. So again, it’s less about where the cancer started or what type of cancer it is, and more about what’s actually driving that cancer’s development. Checking for these tumor-agnostic cancer biomarkers can really help guide treatment decisions for a very wide range of cancers.
2) Could you provide us with an example of a tumor-agnostic biomarker and how testing is done to identify it?
A recent tumor-agnostic biomarker that’s really gaining traction right now is HER2, short for human epidermal growth factor receptor 2. It’s a mouthful. Essentially, this is a protein found on the surface of some cells in your body.
Its primary function is to help cells grow and divide normally, but in some cancers, like breast cancer, there can be too much HER2 protein expression. When that happens, it can cause the cancer cells to grow and spread more quickly. Doctors refer to this as HER2-positive or HER2-overexpressed cancer. The good news is that there are special treatments that target the HER2 protein, helping to slow or stop the cancer from growing.
We used to only look for changes in HER2 expression as a biomarker in breast, stomach, and colorectal cancers. Now, with newer, effective treatments targeting HER2, there’s more research showing that an abundance of HER2 protein can actually be the cause of many different cancer types, like lung cancer, endometrial cancer, and gallbladder cancer. Testing for HER2 changes can help doctors choose treatments that are more likely to work for you, regardless of the type of cancer you have.
Regarding the second part of the question on how HER2 testing is typically done, HER2 testing is performed in a lab using a sample of the tumor, which is usually collected during a biopsy or surgery. In the lab, a special test called immunohistochemistry (IHC) is applied to the tumor specimen. This test puts a stain on the tissue to see how much of the HER2 protein is present on the cancer cells.
If there’s a high amount of HER2 protein on the cancer cells, special doctors called pathologists who help diagnose diseases by studying cells and tissues under a microscope, will generally assign it a score of 3+. Once the 3+ scoring is determined, the cancer is considered HER2-positive or HER2-overexpressed.
3) Is this testing done at the time of diagnosis? If I had a recurrence, would it be necessary to get another biopsy?
If you happen to have a metastatic cancer diagnosis, your oncologist will likely order HER2 testing using a tumor tissue sample that was obtained either through a biopsy or surgery.
The second part of the question was whether you’ll need a rebiopsy or retesting for HER2 at the time of disease recurrence. The simple answer is: not always. We can often use tissue from a previous biopsy or surgery to do the HER2 testing, as long as there’s enough tissue and the sample isn’t too old. That said, if your cancer has come back or spread after prior treatment, your care team might recommend a new biopsy, if possible. This is because tumors can change over time, especially after treatment. So, testing a more recent sample may give us the most accurate picture of what’s going on now.
The good news is that we’re also making a lot of progress with liquid biopsy. Liquid biopsy is essentially a blood test that looks for tumor DNA or cancer cells that are floating in the bloodstream.
In the future, we may be able to measure HER2 changes just through a blood draw, which could really help us avoid the need for another tissue biopsy.
4) How does HER2 influence treatment options for patients?
Tumor-agnostic therapy is a treatment that works based on a specific feature of the cancer, like a genetic marker or a protein, rather than where the cancer started in the body. In this case that we’re discussing, that feature, that “personality,” is the HER2 protein. Traditionally, HER2-targeted treatments were used mostly in breast and stomach cancers.
Last year, the U.S. Food and Drug Administration (FDA) approved a newer HER2-targeted drug called Enhertu, which also stands for trastuzumab deruxtecan, for use in other cancers, like lung, endometrial, or uterine cancer, if they have high levels of HER2 protein. This decision was based on several studies showing that Enhertu helps shrink tumors in about 50% of patients, which is considered a very good response in cancer treatment.
This is a very exciting development because it means that more patients with different types of cancer might benefit from HER2-targeted treatments if there is HER2 protein overexpression, not just those with breast or stomach cancers.
Want to learn more about HER2? View the full webinar recording here.