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Ask the Expert: latest advances in immunotherapy for breast cancer (RECAP)

June 08, 2020

Summary by

Alon Rivel

Outcomes4Me’s Chief Medical Advisor, Dr. Osama Rahma, sat down with Dr. Elizabeth Mittendorf from Dana-Farber Cancer Institute in Boston to answer questions about what breast cancer patients need to know about immunotherapy. Dr. Mittendorf is the Director of the Breast Immuno-Oncology program and Co-Director of the Breast Cancer Clinical Research Program at Dana-Farber/Brigham and Women’s Cancer Center. She is also the Robert and Karen Hale Distinguished Chair in Surgical Oncology and Associate Chair for Research in the Department of Surgery at Brigham and Women’s Hospital. 

We have included the entire video above for anyone who missed it and wants to watch it in full.  Here is a recap of the key takeaways from the discussion with Dr. Mittendorf:

>> What is cancer immunotherapy? how does it work?

Immunotherapy is a type of treatment that is designed to help a patient’s immune system better fight their cancer. There are many types of immunotherapy, including vaccines, CAR T-cells, and immune checkpoint inhibitors, which are most commonly used in solid tumors. 

Your immune system has many “stop” and “go” signals. Cancer has the ability to hide from the immune system by evading these signals. Immunotherapy can help ramp up the immune system “go” signals and block the “stop” signals – this helps your immune system recognize and kill cancer cells. 

>> What makes immunotherapy different from other breast cancer drugs?

There are a number of reasons. Unlike chemotherapy, where you receive treatment and it lasts a short time in your system, immunotherapy can create a long-term (potentially even life-long!) response. This means that immunotherapy can provide therapeutic benefit much longer than other cancer drugs. 

In addition, immunotherapy has different side effects than chemotherapy and other breast cancer drugs. Most patients are aware of the chemotherapy side effects – hair loss, nausea, vomiting, etc. Immunotherapy is different – side effects can happen if your immune system becomes overexcited and causes inflammation. Inflammation can lead to different “itis” side effects, like colitis (inflammation of the colon), thyroiditis (inflammation of the thyroid) and pneumonitis (inflammation of the lungs). We are becoming much more familiar with the side effects of immunotherapy, and most healthcare providers are now quick at recognizing and treating and monitoring side effects that may come up. 

>> is immunotherapy an option for all subtypes of breast cancer?

Historically, we haven’t had as much luck with immunotherapy in breast cancer as we have with skin cancer or lung cancer. However, we are very excited because last year, Tecentriq (atezolizumab) was the first immunotherapy drug approved for advanced and metastatic triple-negative breast cancer that expresses at least 1% of a biomarker called PD-L1.

What we are learning is that immunotherapy works best in cancers that have a lot of mutations, because it is easier for the immune system to recognize and kill the cancer cells. Breast cancer doesn’t tend to have a lot of mutations, but we are currently looking at ways to make breast cancer more responsive to immunotherapy, such as combining it with chemotherapy and looking at tumor characteristics such as the tumor mutation burden (TMB) and microsatellite-instability status (MSS) to see if we can find the patients that will respond well to immunotherapy. 

Right now, most immunotherapy treatments and trials are focused on triple-negative breast cancer. However, my lab is working on ways to make ER+ and HER2+ breast cancers more responsive to immunotherapy. 

>> What percentage of patients will respond to immunotherapy?

Right now, we only have approval for immunotherapy in the TNBC, which is 10-15% of all breast cancers. About 40% of these patients expressed the PD-L1 biomarker. There’s not a lot of absolutes in oncology – so not everyone will respond, and a fair amount of people that respond will eventually progress. But at the end of the day, there are many patients that will potentially benefit, and we are doing ongoing investigations to see how we can make it work for HR+ and HER2+ patients as well. 

>> Could parp inhibitors increase immunotherapy response?

PARP inhibitors are used for BRCA-mutated breast cancer. It means that your DNA can’t repair itself effectively. BRCA-mutated breast cancer seems like the perfect set up for immunotherapy – you have errors in your DNA that your immune system can recognize. 

We conducted initial trials based on this hypothesis and interestingly, these PARP inhibitors also helped stimulate the innate immune response through a pathway called STING. The PARP inhibitors were stimulating the tumor microenvironment to make it more hospitable/kinder to T-cells so they can come in and active an immune response. 

There are a number of ongoing clinical trials, which are very small studies at this point. We do know that combining PARP inhibitors with immunotherapy is safe and that there is an immune response – now we are looking at if there is any clinical benefit to combining the two. 

>> What do you think the future of breast cancer immunotherapy looks like?

I like to say I was into immunotherapy before it was cool – when I started, we only knew of 2 signals in the immune system! The future of immunotherapy looks much brighter. We are investigating different “go” and “stop” signals that we can target within breast cancer by looking at the tumor microenvironment. 

Right now, we have many immunotherapy agents and so many combinations we can try out. It will be critically important for doctors and researchers to thoughtfully choose what we treatments and sequences we think are best. The next step would be to try them out in clinical trials and rigorously study the response of the patients. It’s a tremendous time to be able to work with immunotherapy and there is a lot of work to be done – but I’m hopeful that we will be able to make immunotherapy work for breast cancer patients. 

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