Receptors

When I was initially diagnosed and joined some online support groups, I discovered a whole new short-hand utilized by patients and medical professionals to describe the different subtypes of breast cancer. At first, these letters and symbols were quite intimidating and it took me some time to get comfortable and familiar with utilizing and interpreting the information. Now, I understand far more about them and truly a few pieces of information can go a long way towards understanding the experiences and treatment of each person I meet.

Receptors are usually part of this short hand. Generally, receptors are molecules that live on the surface of a cancer cell that can be filled (and attract) by a specific ligand. This ligand can also colloquially be called “fuel” since when the receptors are filled, that allows the cancer cell to continue to proliferate and take over more healthy cells. If you are interested in learning more about receptors, here’s an article: https://pubmed.ncbi.nlm.nih.gov/12022699/. Fair warning, the explanations can be a bit dense and involved.

For breast cancer, there are three (3) different receptors that are typically used to describe a subtype and which are often targeted for treatment. They are: 1) Estrogen; 2) Progesterone; and 3) Her2 neu. For the first two receptors, both hormones made naturally by the body, a pathology report will include a percentage of positivity. An article with more information about these receptors can be found here: https://www.breastcancer.org/symptoms/diagnosis/hormone_status. For the last receptor, the pathology reports typically just include positive or negative; however, there is some new data/studies looking at a third category of Her2-low, which opens up some additional treatment options. An article explaining a little more about this new landscape can be found here: https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-021-01492-x.

When I was first diagnosed, the pathology report indicated that the original tumor in my breast was strongly estrogen positive (98%), moderately progesterone positive (67%) and Her2-negative. Since the pathologist had to run more than one test to determine the Her2 receptor status, I now understand that the correct terminology is Her2-low for that initial tumor. Researchers understand much more about Her2-low now than in 2017.

For the last 4.5 years, we have proceeded as though the metastases in my bones have the same receptors as that initial tumor. The only other information we had was that the tissue removed from the inside of my femurs to make room for the rods (a/k/a “reemings”) indicated the presence of breast cancer. Otherwise, we’ve literally been guessing as to the right treatment decisions since the bone biopsy was also not successful in giving us any information and the various liquid biopsies merely confirmed the presence of the genetic germline mutation, ATM, that I inherited. ATM does not yet have a specific treatment like the BRCA mutations do. Not yet.

Recently, since we’ve been able to study the cancer cells and lesions that spread to my liver, we have discovered a few new pieces of information that will help guide treatment decisions after this current line. We also, for the first time, have information about a relatively newly understood receptor, the androgen receptor, which is prevalent in hormone positive breast cancer and has become a new target for treatment studies within the last few years. An article that describes this receptor can be accessed here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024330/.

Here’s what we now know about how the metastatic breast cancer in my body has changed over time:

1. The estrogen receptor percentage has gone from 98% to 80%, which doesn’t mean much for treatment decisions. Even when there is a low estrogen percentage, hormone therapy is still used. Estrogen is a very strong receptor generally and we will still be ensuring that the estrogen in my body is as limited as possible. The reduction could mean that I’m on my way to losing this receptor as it is more likely generally to lose receptors than gain them as treatment pushes the cancer to mutate to get around treatment. But we don’t know this or much else for sure.
2. The progesterone receptor has now entirely disappeared. As I understand it, this is not an uncommon situation when a patient has received endocrine therapy since the cancer has had to learn how to get around the blockades caused by the treatment. This may also mean that the intrinsic subtype of the cancer may have mutated from luminal A to luminal B, indicating that the cancer is more aggressive, but also more responsive to IV chemotherapy. Intrinsic subtyping is something utilized more prevalent my in Europe and in trials, but I learned a bit about it while at SABCS in December of 2021. I found this article, while a bit dated, to be a helpful outline of this topic: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656721/.
3. The Her2 status is still low and we’re currently exploring a trial of a cancer vaccine at the Mayo Clinic that has shown some promise in teaching the immune system to target this receptor effectively. The trial information is listed at clinical trials.gov and can be found here: https://clinicaltrials.gov/ct2/show/NCT04246671?term=Chumsri&cond=Breast+Cancer&draw=3&rank=13.
4. The androgen receptor is positive. I don’t have a percentage or more information on this receptor yet, but there are some trials looking at targeting this receptor, which is often positive when the estrogen receptor is positive. Most likely, this is information that we will keep in our back pocket for now.

And with all of this information, we are still proceeding with the original plan, the combination of Taxotere and Xeloda. We will do another PET/CT after the third cycle and then reassess, as always. While there is nothing positive about the cancer spreading, especially into the soft tissue, I am hopeful that the new information will be helpful moving forward and that our treatment decisions will be even more precise.

Proceeding with PERSISTENCE, one step at a time, learning as much as we can along the way. Thankful for all the people who are in my corner, who make sure I know I’m loved and thought about. You know who you are.