breast cancer immunotherapy

In this podcast episode, the host discusses breast cancer and its statistics, different forms of breast cancer, current immunotherapies, and ongoing research. The statistics show that breast cancer is the second most diagnosed type of cancer in Australia, with a high number of individuals diagnosed and deaths reported. There are different types of non-invasive and invasive breast cancer, each requiring different forms of treatment. The podcast also covers the subtypes of breast cancer based on receptor expression, such as HER2-positive and triple-negative breast cancer. Immunotherapy, specifically immune checkpoint inhibitors and monoclonal antibodies, is discussed as effective treatment options for HER2-positive breast cancer. Pembrolizumab, a checkpoint inhibitor, is mentioned as a treatment option for triple-negative breast cancer. Additionally, there is ongoing research on breast cancer vaccines and other immunotherapies. Hello to all my fellow second year science students. My name is Peter Owens. Welcome to Immunovate, your journey into immunology. If you're new to this show, this podcast releases weekly episodes on anything immunology related. This week we have a really special show and I hope you find it as interesting as I do. Today we'll be talking about breast cancer and we'll go into some depth about statistics around breast cancer, what are the different forms of breast cancer, current immunotherapies and what is the current research happening right now as we speak. I'm pleased to say we have some exceptional guests in today who I can say are experts in their respective fields. Firstly we have John Farmer who is from the Australian Institute of Health and Welfare and we also have Dr. Stephen O'Reilly who is the leading oncologist at the Alfred Hospital. So firstly John, why should we care about breast cancer? How prevalent is breast cancer in Australia? Well we just need to look at the statistics behind breast cancer to understand why all of us should care. According to the AIHW, the number of individuals diagnosed with breast cancer in Australia in 2022 was 20,640 and this can be broken down further into 212 males and 20,428 females. It is the second most diagnosed type of cancer preceded by prostate cancer. It is estimated that the percentage of all new cancer cases diagnosed in 2022 that were breast cancer was 12.7%. Moving to the mortality numbers, there were an estimated 3,214 deaths from breast cancer in Australia in 2022 with that being 36 males and 3,178 females. Furthermore, breast cancer is estimated to contribute to 6.4% of all deaths from cancer in Australia. However, the good news is that individuals with breast cancer are seen to have a 92% chance of surviving at least 5 years. Finally, at the end of 2017, in Australia, there is an astonishing 79,720 people living with breast cancer. Now Stephen, for the viewers at home, what specifically is breast cancer? There are many different types and subtypes of breast cancer and each requires different forms of treatment. The first form of breast cancer that I would like to talk about is non-invasive breast cancer or also known as sarcoma in situ. The infected cells look like your typical cancer cells except they have not spread to nearby tissues. If it isn't treated, non-invasive cancer can develop into the more serious invasive breast cancer, which we'll be talking about in a second. So Stephen, what are the types of non-invasive breast cancer? Good question. I'll talk about the two main types of non-invasive breast cancer. Now they are non-invasive in nature as it hasn't spread to any surrounding tissues. This cancer isn't as serious as other forms of breast cancer but can increase an individual's chance of developing invasive breast cancer later in life. The first form of non-invasive breast cancer is ductal sarcoma in situ. It is the most common form of non-invasive breast cancer. It occurs when there is an unusual change in the cells in the milk ducts of the breast. The other common form of non-invasive breast cancer is lobular sarcoma in situ. This is where there is a formation of abnormal cells in the lobules. Now then, what are the different types of invasive breast cancer? The other main form of breast cancer is invasive breast cancer. This is a more serious form of cancer and entails when the cancer cells spread from outside the breast ducts or lobules of the breast and into the surrounding breast tissue. There are two main types of invasive breast cancer, the first being, and the most common of all forms of breast cancer, invasive ductal sarcoma. It accounts for about 80% of all breast cancer diagnosis. The cancer cells that were in the milk ducts of the breast have spread through the lining of the ducts and is spreading into surrounding tissue. Eventually this cancer can spread to the surrounding lymph node if untreated. The second form of invasive breast cancer that is important to state is invasive lobular sarcoma. With this form, the cancer begun in the milk producing lobules but has spread into the surrounding tissues. Like invasive ductal sarcoma, if untreated, it can spread to the lymph node. Stephen, can you go into some depth about the subtypes of breast cancer that you'll be speaking about today? Of course I can. There are two subtypes of breast cancer I'd like to share with you. The subtypes of breast cancer are categorised based on the receptor that a cancer cell can express. This controls how one cancer cell can behave. HER2 positive breast cancer, which is where the breast cancer has too much of a protein called human epidermal growth factor receptor 2, more commonly known as HER2, on the surface of cancer cells. This excess of HER2 promotes the formation of cancer cells. The other subtype is triple negative breast cancer. This is where the cancer cells do not have any of the receptors which are commonly found on a breast cancer cell, those being estrogen, progesterone and HER2. This form of breast cancer is very aggressive and can be quite serious. For this part of the podcast, we'll go into immunotherapy treatments for breast cancer. Firstly, Stephen, can you explain to us what immunotherapy is? Immunotherapy is a type of treatment for cancer that helps your body's immune system fight the cancer. The immune system's main function is to detect and destroy abnormal cells. The immune system can prevent or slow down the growth of cancer cells, however, cancer cells are specialised in finding ways to avoid detection or destruction from our body's immune system. Cancer cells do this by having genetic changes that make them less visible to the immune system, have proteins on their cell surface that can turn off the immune system. So immunotherapy helps in counteracting these abilities of cancer cells. What are the two types of immunotherapies that you'll be presenting to us today? The two main forms of immunotherapy we'll be speaking about is, firstly, immune checkpoint inhibitors, which are drugs that block immune checkpoints. These checkpoints ensure that an immune response is not too strong. Thus, by blocking them, you allow for a stronger immune response to the cancer. The second immunotherapy is monoclonal antibodies, which are created to bind to specific targets on a cancer cell. Monoclonal antibodies have varying effects, such as marking cancer cells so they can be more easily detected by immune cells. They can also trigger an immune response, which can destroy the outer wall of the cancer cell, or they can block cell growth. So what are the immunotherapy options for HER2-positive breast cancer? Immunotherapy has seemed to be very effective for HER2-positive breast cancer. This is mainly via monoclonal antibodies, with those being trastuzumab and pertuzumab. Trastuzumab and pertuzumab are HER2-targeted recombinant humanized monoclonal antibodies. Can you explain to us how these monoclonal antibodies work? Firstly, let's explain how trastuzumab works. This drug binds to the extracellular domain of the HER2 receptor. When it binds to HER2, it prevents HER2 from forming homodimers, which are pairs of HER2 receptors binding to each other. This homodimerization is a critical step in activating HER2-mediated signaling. By blocking it, trastuzumab effectively shuts down this signaling pathway. Trastuzumab also plays an important role in enhancing antibody-dependent cellular cytotoxicity. In simpler terms, it helps the immune cells recognize and eliminate cells that have HER2 receptors on their surface. Now, let's switch the focus to pertuzumab. This monoclonal antibody works by interfering the classical signaling pathway that are triggered by HER2 activation. These pathways involve processes like receptor dimerization, which is HER2 pairing with other receptors, receptor phosphorylation, the addition of phosphate groups of HER2, and the activation of downstream signaling proteins like ERK and ACT. Pertuzumab disrupts these processes, leading to a halt in cell growth and the initiation of apoptosis. Together, both monoclonal antibodies form a powerful combination in a fight against HER2-positive breast cancer. This is because trastuzumab prevents HER2 from transmitting signals that promote cell growth and can help immune cells attack cancer cells. And pertuzumab takes a different approach, interfering with HER2's ability to activate various pathways that encourage cell growth. Now moving to triple negative breast cancer, what are some immunotherapy options available for this form of breast cancer? Yes, one of the drugs used in the treatment of triple negative breast cancer is pembroluzumab. Pembroluzumab is a checkpoint inhibitor which targets a protein called PD-1. Blocking PD-1 is an effective treatment as PD-1 is a T-cell inhibitory receptor that is designed to prevent autoimmunity. However, in a cancer setting, inhibiting this inhibitor will promote stronger immunity. Pembroluzumab targets PD-1 as it binds with very high affinity to PD-1 and antagonizes the interaction it would normally have with PD-L1. Normally the binding of PD-1 and PD-L1 transduces inhibitory signals that reduce T-cell activity. The binding of pembroluzumab to PD-1, which prevents inhibitory pathways, causes there to be an enhanced tumor immunosurveillance and anti-tumor response. So what are some immunotherapies currently in research that could be used for treatment of breast cancer? Currently speaking, there are two recent immunotherapies that have shown positive signs. The first being a breast cancer vaccine. Now I'd like to first mention that cancer vaccines work by stimulating a patient's immune system, which helps the body recognize and destroy tumor cells by presenting tumor-associated antigens and tumor-specific antigens. Now there are no breast cancer vaccines available currently, but the Cleveland Clinic Lerner Research Institution have had some groundbreaking research in the field. The vaccine they are producing will be for individuals with triple negative breast cancer and will target the milk protein alpha-lactalbumin. This protein is normally only expressed in women who are lactating, and once a woman has finished lactating, the protein normally will disappear. However, in 70-80% of individuals with triple negative breast cancer, they will produce too much of alpha-lactalbumin. Thus, the vaccine will flag alpha-lactalbumin and prevent the emerging tumor from growing. Due to limited human trials done so far, it is actually unknown what the side effects will be. And thus, the first phase of human trials will be beginning at the end of the year, and we should get to understand how the side effects will start affecting people. Wow, that's very exciting. Can you explain to us the other form of immunotherapy that's being researched at the moment? The other promising immunotherapy being researched now also targets triple negative cancer. This research involves trimeric antigen receptor, known as CAR-T cell-based immunotherapy. CAR-T cells are designed to harness the patient's immune system to identify and eliminate tumor cells that display specific tumor-associated antigens. CAR-T cells are equipped with customized antibodies that enable them to recognize these antigens within the patient's own tumor cells, leading to their destruction. These modified CAR-T cells possess enhanced receptors which improve specificity and sensitivity, allowing for better identification of cancer cells. Despite its potential, it's worth noting that CAR-T therapy still requires extensive research and development, and initial expectations have not been fully met, and further studies are needed to optimize their outcomes. All in all, these two immunotherapies could be the next wave of treatments for patients with breast cancer. Wow, that's some exciting stuff. Well, I think that's all we have time for here today. I'd just like to thank John and Stephen for sparing a few minutes for us. You both presented some fascinating stuff. And of course, a big thank you to all you listeners for tuning in. Hope you found today's episode both informative and engaging. We'll be back with more exciting content soon. Stay tuned. But until then, goodbye to you all.