Triple negative breast cancer (TNBC) stands as a particularly aggressive and challenging subtype of breast cancer, affecting approximately 15-20% of all breast tumor diagnoses. This form of cancer is more common in younger, pre-menopausal women and is associated with a higher potential for metastasis and recurrence within the first five years after diagnosis. Patients face a significant unmet medical need due to the absence of specific receptors that typically allow for targeted therapies in other breast cancer types. Immunotherapy has emerged as a promising alternative, offering new avenues for treatment in this difficult disease.
Understanding Immunotherapy
Immunotherapy is a cancer treatment approach that empowers the body’s own immune system to identify and eliminate cancer cells. Unlike traditional treatments such as chemotherapy or radiation, which directly attack cancerous cells, immunotherapy works by enhancing the immune system’s natural capabilities. The immune system is constantly surveying the body for abnormal cells, including those that can become cancerous.
However, cancer cells often develop ways to evade this immune detection, sometimes by mimicking healthy cells or by sending “off” signals to immune cells. These “off” signals are mediated by proteins known as immune checkpoints, which act as natural brakes on the immune system. Immunotherapy drugs, particularly immune checkpoint inhibitors, block these signals, effectively releasing the brakes and allowing the immune cells to recognize and attack the cancer.
Immunotherapy’s Specific Role in Triple Negative Breast Cancer
Immunotherapy holds particular relevance for triple negative breast cancer because TNBC cells lack the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). This absence means that TNBC does not respond to hormone therapies or HER2-targeted drugs, which are effective for other breast cancer subtypes, leaving chemotherapy as the main conventional treatment. The aggressive nature of TNBC and its limited traditional treatment options highlight the need for new strategies.
TNBC often exhibits characteristics that make it more responsive to immunotherapy. For instance, these tumors frequently have a higher tumor mutational burden, meaning they carry more genetic mutations. This higher mutational load can lead to the creation of more “neoantigens,” unique proteins on the surface of cancer cells that the immune system can recognize as foreign, thereby making the tumor more visible to immune attack.
Another characteristic is the presence of Programmed Death-Ligand 1 (PD-L1) expression on tumor cells or immune cells within the tumor’s surrounding environment. PD-L1 can bind to the PD-1 protein on immune T-cells, sending an “off” signal that prevents the T-cells from attacking the cancer. Immunotherapy, specifically immune checkpoint inhibitors, blocks this interaction, allowing the T-cells to remain active and destroy the TNBC cells. PD-L1 testing helps identify patients who may benefit from these treatments.
Current Immunotherapy Approaches for TNBC
Current immunotherapy for TNBC primarily involves immune checkpoint inhibitors, often used in combination with chemotherapy. Two notable immune checkpoint inhibitors are pembrolizumab and atezolizumab.
Pembrolizumab has received approval for use in high-risk, early-stage TNBC when combined with chemotherapy as a neoadjuvant treatment (given before surgery), and then continued as a single agent after surgery. It is also approved for locally recurrent unresectable or metastatic TNBC that expresses PD-L1 with a combined positive score (CPS) of 10 or higher, typically in combination with chemotherapy regimens such as paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin. Atezolizumab, another PD-L1 inhibitor, was previously approved in combination with nab-paclitaxel for unresectable locally advanced or metastatic TNBC with PD-L1 positive tumors, though this accelerated approval was later withdrawn due to confirmatory trial results.
Immunotherapy drugs are typically administered intravenously, meaning they are given directly into a vein. The specific treatment regimen, including the combination chemotherapy and the frequency of infusions, varies based on the patient’s disease stage and other factors. Research continues to explore other emerging immunotherapy approaches for TNBC to further enhance treatment outcomes.
Navigating Immunotherapy Treatment
Undergoing immunotherapy for triple negative breast cancer involves a structured treatment schedule and close monitoring. Treatment cycles and duration can vary, with some regimens involving infusions every few weeks for several months or even longer. Regular medical appointments and tests are scheduled to assess how the body is responding to the treatment and to monitor for any side effects.
Immunotherapy can lead to side effects, often called immune-related adverse events (irAEs), because they result from the immune system becoming overactive and attacking healthy tissues. Common side effects include fatigue, skin rashes, and muscle or joint aches. More serious irAEs can affect various organs, potentially causing inflammation in the thyroid gland (hypothyroidism or hyperthyroidism), colon (colitis leading to diarrhea), lungs (pneumonitis causing cough or shortness of breath), or liver (hepatitis).
Patients are encouraged to promptly report any new or worsening symptoms to their healthcare team. Managing these side effects often involves corticosteroids to reduce inflammation, and in some cases, temporary pauses or dose adjustments of the immunotherapy may be necessary. A multidisciplinary care team, including oncologists, nurses, and other specialists, works together to manage treatment and address any adverse events, ensuring comprehensive patient support.