Immunotherapy is a transformative approach in cancer treatment that leverages the body’s own defense mechanisms. This modality works by stimulating the immune system’s natural ability to recognize and eliminate malignant cells. For breast cancer, immunotherapy has significantly expanded treatment options beyond traditional methods like surgery, radiation, and chemotherapy. The therapy aims to enhance the immune response to cancerous tissue, offering hope for challenging breast cancer types.
How Immunotherapy Targets Breast Cancer
The body’s immune system, particularly specialized white blood cells called T-cells, has a built-in capacity to find and destroy abnormal cells, including those that are cancerous. Cancer cells, however, are highly skilled at evading this immune surveillance by exploiting natural regulatory mechanisms known as immune checkpoints. These checkpoints are like “brakes” on the immune system, designed to prevent T-cells from mistakenly attacking the body’s healthy tissues.
One of the most significant checkpoints involves the interaction between the PD-1 protein, found on the surface of T-cells, and the PD-L1 protein, which is often overexpressed by tumor cells. When PD-1 binds to PD-L1, it sends an inhibitory signal that effectively “turns off” the T-cell, preventing it from attacking the cancer cell. The tumor essentially uses the PD-L1 protein as a shield to hide from the immune system.
Immunotherapy drugs block this specific PD-1/PD-L1 interaction, essentially releasing the brakes on the T-cells. Preventing the binding allows the T-cells to remain active and recognize the cancer cells as foreign. This action allows tumor-specific T-cells to proliferate and destroy the cancer.
Types of Immunotherapy Treatments
The primary class of immunotherapy used to treat breast cancer is Immune Checkpoint Inhibitors (ICIs). These agents are monoclonal antibodies designed to interrupt the inhibitory signals that cancer cells use to protect themselves from immune attack. Specifically, ICIs target either the PD-1 protein on T-cells or the PD-L1 protein on the cancer cells.
For breast cancer, drugs like pembrolizumab (anti-PD-1) and atezolizumab (anti-PD-L1) have received regulatory approval for use in specific patient populations. Pembrolizumab, for example, binds to the PD-1 receptor on the T-cell, blocking the cancer cell’s PD-L1 protein from engaging with it.
While ICIs are the current focus, other immunotherapy approaches are also being explored for breast cancer. Therapeutic cancer vaccines are a promising area of research, designed to stimulate the immune system to recognize specific tumor-associated antigens. Monoclonal antibodies that function as immune stimulators, such as trastuzumab for HER2-positive breast cancer, are also considered a form of immune-targeted therapy. They recruit the immune system to destroy the cancer cells after binding to a specific target.
When Immunotherapy is Used
Immunotherapy is not a universal treatment for all breast cancers but has a defined and significant role in specific subtypes. It is currently most established in the treatment of Triple-Negative Breast Cancer (TNBC), an aggressive form that lacks the estrogen, progesterone, and HER2 receptors. TNBC tumors often have higher levels of immune cell infiltration and PD-L1 expression, making them more susceptible to checkpoint inhibition.
In the early-stage setting, immunotherapy is often combined with chemotherapy before surgery, known as neoadjuvant therapy, for patients with high-risk TNBC. Following surgery, patients may continue to receive the immunotherapy drug alone as adjuvant therapy to help prevent recurrence. For metastatic (advanced) TNBC, immunotherapy is also used in combination with chemotherapy, but patient eligibility is often determined by the expression of the PD-L1 protein on the tumor cells.
A biomarker test is performed on the tumor tissue to determine the level of PD-L1 expression. This helps predict which patients are most likely to benefit from the treatment. A high expression of PD-L1, often defined by a specific threshold, is required for the use of ICIs in the metastatic setting. Immunotherapy has a less defined role in the more common hormone receptor-positive or HER2-positive breast cancer subtypes, though it may be considered for patients with rare tumor characteristics.
Managing Treatment Side Effects
The unique mechanism of immunotherapy leads to a distinct set of side effects compared to traditional chemotherapy. By activating the immune system, these treatments can sometimes cause the immune cells to mistakenly target and attack healthy organs and tissues, resulting in what are known as immune-related adverse events (irAEs). These irAEs can affect almost any organ system in the body, but they most commonly involve the skin, colon, and endocrine glands.
Common side effects include fatigue, skin rash, and diarrhea. Less frequent but more serious issues can involve inflammation of the colon (colitis) or hormone-producing glands (endocrinopathies).
The strategy for managing moderate to severe irAEs involves temporarily stopping the immunotherapy. This is followed by administering corticosteroids, which are powerful anti-inflammatory drugs used to suppress the immune response. Patients must report any new or unusual symptoms immediately, as early intervention is important to control inflammation and prevent serious organ damage.