The Evolving Landscape of Immunotherapy in Breast Cancer Treatment
Breast cancer remains the most commonly diagnosed malignancy in women, with over 2.3 million new cases reported in 2022. Whereas traditional treatments like chemotherapy have long been the standard, immunotherapy is rapidly emerging as a powerful tool, particularly for specific subtypes. Historically, breast cancer was considered less responsive to immunotherapy due to factors like lower tumor mutational burden, but recent successes in other cancers and a deeper understanding of the disease are changing that perception.
Immunotherapy’s Breakthrough in Triple-Negative Breast Cancer (TNBC)
The most significant advances in breast cancer immunotherapy have been seen in triple-negative breast cancer (TNBC), a particularly aggressive form lacking estrogen receptors, progesterone receptors, and HER2 amplification. Pembrolizumab, a PD-1 blocking antibody, has shown promise, especially when combined with chemotherapy. The KEYNOTE-355 trial demonstrated a significant improvement in progression-free survival for patients with a PD-L1 combined positive score (CPS) greater than 10 when treated with pembrolizumab plus chemotherapy.
Early-stage TNBC is also benefiting from immunotherapy. Trials like KEYNOTE-522 have shown a statistically significant increase in pathologic complete response (pCR) rates with the addition of pembrolizumab to neoadjuvant chemotherapy, and long-term data indicates higher overall survival rates. Biomarkers like tumor mutational burden (TMB) and the presence of tumor-infiltrating lymphocytes (TILs) are being investigated to predict which patients will respond best.
Expanding Immunotherapy to Hormone Receptor-Positive (HR+) Breast Cancer
While HR+ breast cancer historically showed limited response to immunotherapy, recent research suggests potential benefits, particularly in specific cases. Trials are exploring combinations of immunotherapy with targeted therapies, and chemotherapy. The KEYNOTE-756 and CheckMate-7FL trials have shown improvements in pathologic complete response rates with the addition of pembrolizumab and nivolumab, respectively, to neoadjuvant chemotherapy. Though, the long-term benefits regarding event-free survival are still under investigation.
Identifying the right patients for immunotherapy in HR+ breast cancer is crucial. Research is focusing on biomarkers, such as the ImPrint signature identified in the I-SPY 2 trial, to predict which patients are most likely to respond. The potential for toxicity when combining immunotherapy with CDK4/6 inhibitors is also being carefully evaluated.
Emerging Strategies: Bispecific Antibodies and Beyond
The field of immunotherapy is constantly evolving. Bispecific antibodies, designed to target both cancer cells and immune cells, are showing promising results. Ivonescimab, combined with chemotherapy, has demonstrated high overall response rates in metastatic TNBC. Researchers are also exploring combinations of anti–PD-1/PD-L1 and anti-VEGF bispecific antibodies.
Further advancements include investigating the role of antibody-drug conjugates (ADCs) in combination with immunotherapy, particularly for patients with residual disease after neoadjuvant treatment. Trials like OptimICE-RD are evaluating the addition of sacituzumab govitecan (SG) to pembrolizumab in this setting.
De-escalating Treatment: A New Approach
Alongside exploring new combinations, researchers are also investigating whether existing treatments can be streamlined. The SCARLET trial is evaluating whether the chemotherapy backbone used in KEYNOTE-522 can be simplified without compromising efficacy. Similarly, the OptimICE-pCR trial is studying whether adjuvant immunotherapy is necessary for patients who achieve a pathologic complete response after neoadjuvant treatment.
Frequently Asked Questions
- What is immunotherapy?
- Immunotherapy helps your immune system fight cancer by boosting its ability to recognize and destroy cancer cells.
- Is immunotherapy right for all breast cancer patients?
- Currently, immunotherapy is most effective for certain subtypes, particularly triple-negative breast cancer. Research is ongoing to expand its use to other subtypes.
- What are the common side effects of immunotherapy?
- Common side effects include rash, diarrhea, and fatigue. Your doctor will discuss potential side effects and how to manage them.
- What are biomarkers and why are they important?
- Biomarkers are measurable substances that can support predict a patient’s response to immunotherapy. They help doctors identify who is most likely to benefit from treatment.
The future of breast cancer treatment is increasingly focused on personalized approaches, leveraging the power of the immune system to fight this complex disease. Ongoing clinical trials and research into novel biomarkers and treatment combinations promise to further refine and expand the role of immunotherapy in improving outcomes for patients with all subtypes of breast cancer.
Want to learn more? Explore additional resources on Cancer.org and BreastCancer.org.
