Study Reveals Why Triple Negative Breast Cancer Is Resistant to Immunotherapy

Most breast cancer patients end up going through a lot of different treatments during their attempted recovery. Chemotherapy, surgery, immunotherapy, and more are often performed on just one patient. One particular problem that doctors have noticed is that one particular subtype of breast cancer, called "claudin-low" breast cancer is especially resistant to immunotherapy drugs. Researchers wanted to find out why this was happening, and if there was a possible solution to the problem.

What is Immunotherapy?

Immunotherapy is a term that many are not familiar with. In order to understand the study, one must understand immunotherapy and how it works.

We're going to give you a quick explanation of what it is, how it works, and the possible downfalls and consequences it can have.

At its core, immunotherapy is about increasing the immune system's response and effectiveness in getting rid of different types of cancer. This can be done through certain drugs and medications, or in some cases through antibodies that are injected straight into the bloodstream.

The main problem with immunotherapies is that the most effective ones have to be injected straight into the bloodstream through a vaccine. There have been some complications in previous treatments that have caused patients to have itching, swelling, pain, redness, and soreness around the site of the injection. In some cases, the immune system will become overactive and cause similar symptoms to the flu. This includes fever, chills, weakness, fatigue, dizziness, nausea and vomiting, or diarrhea. All in all, these side effects are fairly rare, and are not life threatening. They can be well worth it if it means that your breast cancer is gone.

The other issue with immunotherapy is it is still developing annually, which means that it is expensive. Furthermore, many immunotherapy treatments are in the pre-trial/experimental stage, so there may be only a few patients who can receive the treatment. Since there haven’t been too many studies on the effects of immunotherapy, doctors are hesitant to jump right into immunotherapy with most of their patients. Thankfully, immunotherapy is showing to be effective in most trials and is steadily gaining ground as a fundamental part of breast cancer treatment. The study described below is just one example of how immunotherapy is being improved, and how it may very well be the next step in eliminating breast cancer for good.

Different Types of Breast Cancer

Before we get into the details of the study, we want to take a moment to explain the different types of breast cancer and what exactly they entail.

Ductal Carcinoma in Situ: This is a non-invasive breast cancer that develops in the lining of the breast milk duct. It is very treatable when caught early, but over time the cancer can spread and become much more serious (In Situ means the earliest stages).

Invasive Ductal Carcinoma: This form of cancer is when the cancer cells spread from the lining of the breast milk duct to other parts of the breast tissue. These cancer cells can then spread to other parts of the body. This is by far the most common form of breast cancer, making up nearly 80% of breast cancer diagnoses. It also is the main form of breast cancer that affects men.

Triple Negative Breast Cancer: When cancer cells and tumors are found in the breast tissue, doctors will normally test for receptors of estrogen, progesterone, and the HER-2/neu gene. This is because these three hormones are normally responsible for tumor growth. Usually when doctors find one of these receptors they can provide treatment by decreasing the receptors so that the hormones become balanced (this prevents the creation of more cancer cells). Triple negative breast cancer is where the cells and tumors test negative for all three of those receptors. This can be a problem because most typical treatments revolve around targeting one of those receptors.

Inflammatory Breast Cancer: This type of breast cancer is rarer as it only affects the skin of the breast. Cancer cells infiltrate the skin and block the lymph vessels in the skin. The big problem with this is that this infiltration does not cause the appearance of lumps or other ways to easily detect breast cancer. Most diagnoses for IBC come after patients complain about breast cancer symptoms without showing signs of lumps. These symptoms can vary from case to case. Sometimes the breast will become red, swollen, and itchy. Other times the breast will appear pitted (look like an orange peel). Sometimes there will be a change in the nipple, like a flattening or dimpling.

Metastatic Breast Cancer: This is when breast cancer cells spread to other parts of the body. This is considered stage 4 of breast cancer. Hopefully you will not get to this point, as it is the most dangerous stage of breast cancer. Regular checkups and feeling for lumps often will allow you to catch the cancer much quicker and prevent MBC from happening.

The Study

Researchers wanted to figure out why triple negative breast cancers were not being receptive to immunotherapy. Researchers specifically looked at "claudin-low" triple negative breast cancer, which was a subset that had elevated numbers of immune cells around the tumors and cells. This perplexed researchers, as they assumed that the extra immune cells would help the body fight off the tumors and cells more easily. As it turns out, they were wrong.

The Results

Researchers actually found that the immune cells were inhibiting the immunotherapy. A typical round of immunotherapy involves removing the immune system's brakes against cancer (allowing the T cells to target the cancer at full force). After multiple tests and thorough analysis, researchers concluded that these triple negative claudin low tumors were attracting regulatory T cells (which typically repress the body's natural defenses against cancer). The presence of these regulatory T cells was preventing the immune system from rejecting and attacking the cancer cells.

Is There a Solution?

The researcher's finding posed a huge threat to treating triple negative breast cancer. This led them to search for a possible solution to the large number of regulatory T cells. Researchers attempted to find a way to deplete these regulatory T cells, which would allow the immune system to properly attack and destroy tumors and cancer cells. Researchers found that when regulatory T cells were depleted through the use of drugs, immunotherapy became much more effective. Researchers believe this could be groundbreaking in administering immunotherapy to triple negative breast cancer patients, and that regulatory T cells should be depleted before any immunotherapy.

Final Thoughts

This study proves to be very beneficial in finding a crucial weakness of immunotherapy, and providing a possible solution to the problem. More research will need to be done on how to effectively reduce regulatory T cells, and the possible side effects and consequences of doing so. Still, this study should give hope that there may be a more effective treatment for triple negative breast cancer in the works. Once immunotherapy is more widespread, fighting breast cancer might just be a whole lot easier. For more information on breast cancer and other diseases, be sure to check out the rest of our website.

References

https://medicalxpress.com/news/2017-08-immune-cells-contribute-treatment-resistance.html

https://www.jci.org/articles/view/90499

http://www.onclive.com/web-exclusives/hope-rises-for-immunotherapy-in-breast-cancer

https://www.cancer.gov/about-cancer/treatment/types/immunotherapy

https://www.cancerresearch.org/we-are-cri/home/cancer-types/breast-cancer

http://www.nationalbreastcancer.org/types-of-breast-cancer