Understanding the Impact of Age on Response to Immunotherapy in Breast Cancer
Abstract
Our project is designed to tackle the overarching challenge: Revolutionizing treatment regimens by replacing them with ones that are more effective, less toxic, and impact survival. Recent clinical trials have indicated that immune checkpoint blockade (ICB) therapy could be revolutionary for treating breast cancer patients, especially those with metastatic triple-negative breast cancer (TNBC), a highly aggressive form of breast cancer with few viable treatment options. ICB therapy is designed to unleash a patient’s immune system to attack cancer. Nevertheless, ICB therapy is still ineffective for most breast cancer patients and so efforts are directed at finding ways to improve it. Most breast cancer clinical trials are focused on testing various chemotherapies to identify ones that make ICB work better. However, we believe that there are better ways to improve ICB than to use harsh chemotherapies and that we can identify more effective drugs if we understood more about a patient’s immune status. We contend that age is an important consideration with respect to ICB, given that normal aging is associated with profound changes to the immune system. However, because so few older patients are enrolled in clinical trials, it is not known whether ICB will benefit patients of all age groups. In fact, the vast majority of breast cancer patients enrolled in clinical trials are under the age of 60, yet most breast cancer patients are over the age of 60. Until our own recently published work that supports this proposal, no clinical or laboratory studies had reported whether the effectiveness of ICB is different with age in breast cancer. Our studies support the idea that ICB may not be as successful for older breast cancer patients as it is for younger patients and that other treatments need to be studied in order to help older patients. We propose to conduct studies to follow these important findings and expand them to other breast cancer types. For our project, we propose to use breast cancer cells, preclinical age-dependent breast cancer models, and breast cancer patient data and tissue specimens in order to test new therapeutic strategies before evaluating them in patients. We propose to identify existing drugs that improve responses to ICB in aged mice that could eventually be used to help patients. Assessing the immune changes that occur with age could provide a foundation for effectively applying ICB to breast cancer patients of all ages. A team of experts in breast cancer laboratory research, breast cancer clinical and surgical oncology, and consumer advocacy support this project. Our study is designed to leverage opportunities for immediate clinical translation of our research findings. Ultimately, we hope to provide a basis for improved clinical trial design and help oncologists make decisions about treatment options using ICB. Success in our endeavors has the potential to save lives by delivering the promise of immunotherapy to even more breast cancer patients than are currently seeing benefit.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010472
Entities
People
- Sandra S McAllister
Organizations
- United States Army