Breast cancer affects 1 in 3 women each year, making it the most common malignancy among women worldwide. For men, while the lifetime risk is about 1 in 833, the stigmatization of male breast cancer often leads to late-stage diagnoses.
To combat cancer progression and save lives, clinical researchers have been on a mission to discover new treatments, delving into uncharted or previously “taboo” territories. The U.S. Food and Drug Administration (FDA) has also begun acknowledging alternative therapeutic strategies to fight cancer, and several oncologists are on board.
The lines separating conventional and alternative breast cancer treatments are slowly but surely blurring. In this comprehensive guide, we are focusing on immunotherapy for breast cancer — a topic of growing relevance for patients and medical professionals.
What Is Immunotherapy?
Immunotherapy is a form of cancer treatment that uses the body’s immune system to target and combat cancer cells.
In comparison, conventional treatments like surgery, chemotherapy, and radiation therapy stop or slow cancer cells from growing and multiplying. However, it can also damage healthy cells and cause side effects, including nausea, diarrhea, hair loss, and peripheral neuropathy, among others.
Immunotherapy for breast tumors boosts the body’s defenses, helping the immune system find and destroy cancer cells on their own. Plus, it minimizes damage to healthy cells.
Why Can’t the Immune System Attack Breast Cancer On Its Own?
The immune system often needs assistance from immunotherapy medicine because:
- A breast cancer cell originates as a normal, healthy cell: Cells in the precancerous and early stages of breast cancer do not exhibit visual differences from normal, cancer-free cells, tricking the immune system into thinking that everything is fine. However, as these cells progress toward becoming cancerous, they begin producing proteins that the immune system identifies as “foreign” antigens. In certain instances, the immune system detects these malignant cells as threats and intervenes before cancer can advance.
- As cancer progresses, it “learns” how to avoid immune system detection: Breast cancer evolves gradually over time. During the transition from normal, healthy cells to cancerous entities, the genetic information within these cells undergoes constant alterations. Some of these genetic changes grant cancer cells the ability to evade detection by the immune system. Meanwhile, other changes enable these cancer cells to accelerate their growth and multiplication, far outpacing the rate of normal cells. This rapid proliferation can overwhelm the immune system’s defenses, ultimately permitting unchecked growth of breast cancer.
Learn more about the human immune system, how it works, and how immunotherapy can take advantage of its mechanisms here.
How Does Immunotherapy for Breast Cancer Work?
The immune system works 24/7/365, protecting the body from foreign substances or invaders, including germs, viruses, allergens, and damaged cells that could evolve into cancer. It has “special enforcers” (T cells) that continuously patrol the body for intruders. If they encounter a damaged or malignant cell, they try to kill it to prevent further growth and spread. But because cancer is an intelligent species with adaptive capabilities, as discussed, it can find ways to evade the immune system’s radar. Immunotherapy medicine “sharpens” the immune system’s ability to detect and destroy breast cancer cells.
Keep in mind that there are different types of breast cancer, including but not limited to:
- Ductal Carcinoma In Situ (DCIS)
- Invasive Ductal Carcinoma (IDC)
- Invasive Lobular Carcinoma (ILC)
- Inflammatory Breast Cancer (IBC)
- Triple-Negative Breast Cancer (TNBC)
Each of them has distinct biological traits and behaviors. Immunotherapy targets these specific breast cancer characteristics, making it a groundbreaking advancement in the field of oncology.
Related: The Battle Within: How Immunotherapy for Cancer Works
What Are the Types of Immunotherapy?
Immunotherapy drugs have two main groups: Active and Passive.
Active Immunotherapies for Breast Cancer
Active immunotherapy drugs stimulate the immune system to respond to cancer’s presence. Lab researchers collect cells from cancer for the purpose of finding antigens specific to that tumor. After which, they develop immunotherapy medications that help the body find and target those antigens.
Passive Immunotherapies for Breast Cancer
Passive immunotherapy drugs are laboratory-made immune system components given to a host to help fight a disease. They do not stimulate the human immune system to respond like active immunotherapies do.
Below are examples of active and passive immunotherapies. Keep in mind that many of them are unavailable, as clinical trials in countries like the U.S. are ongoing. But you can contact New Hope Unlimited for information on what complementary and alternative therapies are currently available via medical tourism. Rest assured that our immunotherapy treatments are rooted in several years of scientific research.
1. Breast Cancer Vaccines
Vaccine development and testing focus on exposing the immune system to a specific antigen. It aims to activate immunological memory, rapidly allowing the immune system to recognize and combat the same antigen during future encounters.
Vaccination, a tried-and-true method for preventing infectious diseases, has found an extended purpose in cancer prevention and treatment. Preventive vaccines target viruses that play a role in cancer occurrence (e.g. human papillomavirus and cervical cancer) or antigens expressed early in tumor formation. On the other hand, therapeutic vaccines typically zero in on known cancer antigens.
The fundamental mode of antigen exposure involves intramuscular delivery of synthetically produced peptide antigens. While peptide vaccines are customizable, cost-effective, and easy to produce, they have limitations and are currently in development. Injected peptides are prone to microbial degradation, and their ability to stimulate an immune response can vary.
Nonetheless, recent work from the University of Washington’s Cancer Vaccine Institute, part of the Cancer Consortium Breast & Ovary Cancers Program, revealed that the day breast cancer vaccines become available might not be as distant as it might seem. In Phase 1 of the study published in JAMA Oncology, the researchers shared positive results from their nonrandomized trial for a breast cancer vaccine in advanced-stage ERBB2-positive breast cancer patients. After a 10-year post-vaccine monitoring period, the vaccine demonstrated safety and effectiveness, and most participants remain free from cancer today. Despite the trial’s small sample size, the outcomes are exceptionally promising.
2. Adoptive Cell Therapy
Adoptive cell therapy (ACT) involves isolating a cancer patient’s immune cells, typically T cells, and either enhancing or reprogramming them to target and attack cancer cells. These modified immune cells are then reintroduced into the patient to improve their immune system’s cancer-fighting ability. CAR T-cell therapy is one of ACT’s main types.
The Chimeric Antigen Receptor T-cell, known as CAR-T, is a specialized type of T-cell designed to recognize a specific target antigen and then transmit an activating signal within the CAR-T cells. Each T-cell transforms into an antigen-specific killer T-cell, dedicated to combating the identified threat.
Immunologists develop CAR-T cells by genetically engineering an antigen-binding component, known as a single-chain variable fragment (scFv), into the surface of T cells. This modification allows the T-cells to target and eliminate cancer cells. CAR T-cell therapy also offers the promise of minimal toxicities with the advantage of long-term immune protection.
Progress in antibody genetic engineering and the detailed profiling of malignant cells have yielded diverse bispecific antibodies. Over the past quarter-century, substantial strides were made in developing and applying bispecific antibodies, both for intravenous and localized administration, structuring the field of breast cancer immunotherapy.
3. Oncolytic Virus Therapy
Oncolytic viruses have the extraordinary ability to target cancer cells and support immune cells. The idea to turn oncolytic viruses into cancer therapies stems from two disciplines: virology and immunology, and identifying tumor-associated antigens.
Lab researchers genetically engineer these viruses to enter tumor cells through altered target receptors, or by exploiting faulty signaling in cancer cells. By manipulating viral nucleic acid and protein mechanisms, they take advantage of the higher enzyme expression in rapidly dividing tumor cells compared to normal cells.
Once inside the patient’s body, oncolytic viruses infect and replicate within tumor cells, causing their death. This process also exposes viral antigens on the cells’ surface, activating virus-specific T cells to eliminate the cancer.
The breakdown of cell membranes by oncolytic viruses functions similarly to a whole tumor cell vaccine, contributing to a broader anti-tumor immune response by releasing tumor-associated antigens. These antigen-presenting cells then process these antigens, a phenomenon known as epitope spreading.
There is currently one FDA-approved oncolytic virus therapy: T-VEC (Imlygic®), an altered herpes simplex virus, for melanoma. It remains under investigation for the treatment of other cancers.
4. Cytokines
Cytokines are cell-signaling proteins. They function as messengers between cells to regulate the immune response. Some cytokines, including interferons and interleukins, have demonstrated anti-tumor effects and hold promise as immunotherapies for breast cancer.
- Interleukin-2 (IL-2): IL-2 is a pleiotropic cytokine that T cells produce. It promotes further growth and differentiation of activated T cells and natural killer (NK) cells, enabling them to identify and destroy malignant cells. In clinical trials, IL-2 has demonstrated partial or complete responses in patients with metastatic cancer. However, the likelihood of capillary leak syndrome developing due to systemic IL-2 administration has limited its use, urging scientists to continue investigating the protein to reduce side effects and increase effectiveness.
- Interferon (IFN): IFN is a protein that inhibits tumor cell proliferation and boosts immune surveillance. It arises from the body’s cells as a defensive response to germs, viruses, and other invaders. While its anti-tumor effects are in ongoing clinical trials, it has already shown immune-modulatory and antineoplastic properties when administered to patients with breast cancer.
While cytokines show promise as breast cancer treatments, more research is necessary to determine optimal administration strategies, proper patient selection, potential side effects, and drug interactions.
5. Immune Checkpoint Inhibitors
To activate an immune system response against foreign intruders, the immune system must distinguish between “self” (part of the body) and “non-self” (potential threats). Proteins on or within our body’s cells help the immune system identify what “self” is.
Some of these immune system recognition proteins are known as immune checkpoints. Cancer cells often use these immune checkpoint proteins as a shield to evade detection and attack by the immune system.
Going back to T cells, this immune cell patrols the body for signs of disease or infection. When T cells encounter other cells, they scrutinize specific surface proteins, aiding in the identification process. If these surface proteins signal that a cell is normal and healthy, T cells leave it undisturbed. However, if the surface proteins suggest the cell is cancerous or unhealthy, T cells initiate an attack. As T cells launch an attack, the immune system produces specialized proteins to prevent damage to normal cells and tissues. These protective proteins are known as immune checkpoints.
Immune checkpoint inhibitors target these immune checkpoint proteins to recognize and attack cancer cells more effectively. They disable the inhibitory mechanisms within the immune system, blocking checkpoint inhibitor proteins on cancer cells or the T cells responding to them.
One such group of inhibitors includes PD-1 and PD-L1. PD-1, found on T cells, binds to PD-L1, a checkpoint protein on many healthy cells, impeding T cell activity. However, some cancer cells exhibit high levels of PD-L1 on their surface, preventing T cells from attacking them. Immune checkpoint inhibitors that prevent PD-1 from binding to PD-L1 allow T cells to attack these cancer cells. Notable PD-1 and PD-L1 inhibitors include Keytruda, Jemperli, Opdivo, Bavencio, and Imfinzi.
Another checkpoint protein is CTLA-4, found on certain T cells, which, when binding to the B7 protein on another cell, interferes with T cell activity. Inhibitors like Yervoy target CTLA-4, preventing it from binding to B7, therefore, activating T cells to attack cancer cells. Yervoy is FDA-approved for advanced-stage skin cancer and is under investigation for use in breast tumors and other malignancies.
Clinical trials are still investigating the application of PD-1/PD-L1 and CTLA-4 inhibitors in breast cancer treatment. Oncologists are expecting more FDA-approved immunotherapy medication in the near future.
6. Monoclonal Antibodies
Monoclonal antibodies identify specific target proteins on the cancer cell surface, blocking their function and leading to cancer cell death. Among the FDA-approved monoclonal antibodies for breast cancer include:
- Herceptin® (chemical name: trastuzumab): Herceptin targets HER2-positive breast cancer cells. It obstructs cancer’s ability to receive growth signals by attaching to the HER2 receptor. Herceptin is also available as an injection (Herceptin Hylecta). Moreover, several Herceptin biosimilars are available for breast cancer patients, including Ogivri, Ontruzant, Kanjinti, Herzuma, and Trazimera.
- Enhertu® (chemical name: fam-trastuzumab-deruxtecan-nxki): This combination therapy contains an anti-HER2 medicine similar to Herceptin. Enhertu delivers topoisomerase I inhibitors (anticancer agent) to cancerous cells by connecting it to the anti-HER2 medicine, enabling the targeted administration of chemotherapy to HER2-positive cancer cells.
- Perjeta® (chemical name: pertuzumab): Oncologists often prescribe this drug in combination with Herceptin to target HER2-positive breast cancer cells, impeding their growth signals by binding to the HER2 receptor.
- Kadcyla® (chemical name: T-DM1 or ado-trastuzumab emtansine): Kadcyla combines Herceptin and emtansine. It delivers emtansine, a chemotherapy drug, to HER2-positive cancer cells by appending it to Herceptin, which binds to the HER2 receptors in cancer cells. This combination therapy delivers emtansine directly to the malignant tumor.
- Trodelvy® (chemical name: sacituzumab govitecan-hziy): This anticancer drug combines the following: A monoclonal antibody that targets the Trop-2 protein on metastatic breast cancer cells, the chemotherapy drug SN-38, and a linking compound that attaches the monoclonal antibody to SN-38. Trodelvy delivers chemotherapy drugs to cancer cells in a direct manner, minimizing damage to healthy cells.
- Phesgo® (chemical name: pertuzumab, trastuzumab, and hyaluronidase-zzxf): This fixed-dose combination of Herceptin and Perjeta, along with hyaluronidase-zzxf, treats all stages of HER2-positive breast cancer when integrated with chemotherapy. Oncologists administer the drug through a subcutaneous injection in the thigh.
Takeaway: Does Immunotherapy Work for Breast Cancer?
The role of immunotherapy in the treatment of breast cancer is a subject of ongoing research, with several factors contributing to the complexity of its implementation. The impact of immunotherapy on the diverse types and stages of breast cancer remains a topic of exploration, and the optimal treatment duration has yet to be established. Due to the gradual nature of immune system activation, the timeline for effective responses can be protracted, making it challenging to determine the ideal treatment duration.
To expedite a robust immune response against cancer, experts are investigating the synergistic potential of combining different immunotherapies, such as pairing a vaccine with a checkpoint inhibitor. Additionally, integrating immunotherapies with other established cancer treatments, including targeted therapies, holds promise for enhancing the overall therapeutic approach.
For now, the FDA has approved a few immunotherapies for breast cancer treatment. Keytruda is for early-stage triple-negative breast cancer, while Trodelvy targets specific cases of metastatic breast cancer.
Numerous ongoing trials continue to explore the potential of immunotherapy for breast cancer treatment. For the most up-to-date information on cancer research, regularly check newhopemedicalcenter.com/our-latest-news/.
Is Immunotherapy Right for You?
Anticancer immunotherapy treatments are quite new compared to conventional approaches, but they have the potential to cure and end hundreds of different cancers. Actually, immunotherapy might be able to address your cancer concerns now. The New Hope Unlimited team has been exploring immunotherapy for much longer than modern-day researchers in the U.S. and other developed countries. If you’re interested in immunotherapy for breast cancer (or any other malignant disease), dial 480-757-6573 to schedule an appointment, meet our healthcare team, and explore your treatment options.
