Titles and Affiliations
Professor, Medicine and Radiation Oncology
Co-Director of Breast Cancer Program
Chief, Industry Partnerships
Houston Methodist Academic Institute
Research area
Developing radiation-based strategies to augment anti-tumor responses in high-risk breast cancer.
Impact
Immunotherapy and chemotherapy are standard-of-care therapies in non-metastatic, triple negative breast cancer, yet 35% of patients do not respond to treatment. An unmet clinical need for novel and safe therapies to overcome immune-resistance and augment the effectiveness of immunotherapy exists for this group of patients. Pre-clinical studies have shown that radiation therapy has the potential to convert a non-responsive (immunogenically cold) tumor into a responsive (immunogenically hot) one. However, the optimal dose to stimulate a productive immune response had not been tested or identified in breast cancer patients. Dr. Ho and her team’s work will provide a critical step towards developing precision radiotherapy, facilitating its use in combination with immunotherapy as a successful and durable treatment approach for high-risk breast cancer patients.
Progress Thus Far
With funding from the Breast Cancer Research Foundation (BCRF), Dr. Ho and colleagues initiated and completed the P-RAD clinical trial, a multi-institutional, national phase II randomized study evaluating different radiation dose regimens in combination with immunotherapy to “prime” breast tumors for improved responses to immune checkpoint blockade and chemotherapy. The trial enrolled 104 patients with node-positive triple-negative or high-risk hormone receptor–positive breast cancer across nine institutions in the United States.
Primary results from the high-risk hormone receptor–positive cohort demonstrated that the addition of radiation therapy significantly increased immune cell infiltration in tumors that lacked immune cells prior to treatment, effectively converting an “immune-cold” tumor microenvironment into an “immune-rich” state. This transition was associated with the emergence of distinct immune gene expression profiles and the formation of tertiary lymphoid structures within the tumor microenvironment. Primary results from the triple-negative breast cancer (TNBC) cohort also showed that the addition of radiation therapy significantly increased immune cell infiltration, and the TNBC cohort showed high rates of pathologic complete response in the low-dose radiation arm.
What’s next
Biomarker analyses and transcriptomic analyses are continuing. Insights from P-RAD will inform the development of more effective treatment strategies, including the use of pre-operative radiation to stimulate anti-tumor immunity in combination with emerging immunotherapies.
Biography
Alice Ho, MD, MBA is a Professor of Radiation Oncology and Medicine at the Houston Methodist Academic Institute and a member of the O’Neal Comprehensive Cancer Center. She serves as Co-Director of the Breast Cancer Program at Houston Methodist Hospital, Chief of Industry Partnerships, and Clinical Co-Lead of the Triple-Negative Breast Cancer Personalized Vaccine Program at the Houston Methodist Academic Institute. Dr. Ho earned her joint MD and MBA in Health Administration from Tufts University School of Medicine.
Her clinical practice is dedicated exclusively to the care of patients with breast cancer. Her research focuses on understanding how local cancer therapies can be strategically combined with biologic agents and immunotherapies to elicit systemic anti-tumor immune responses.
