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Lajos Pusztai, MD, D.Phil
Professor of Medicine
Chief, Breast Medical Oncology
Co-Director, Yale Cancer Center Genetics and Genomics Program
Yale School of Medicine
New Haven, Connecticut
Member, BCRF Scientific Advisory Board
Goal: To identify combination treatments that will improve the effectiveness of immunotherapy in patients with aggressive breast cancers.
Impact: Dr. Pusztai’s work is focused on understanding the effects of treatment on the composition of immune cells in breast tumors to identify novel combination strategies to improve response to immune-based therapies.
What’s next: He and his colleagues will study changes in the tumor genome and the immune environment in patients with triple negative breast cancer (TNBC) who were treated with the immune checkpoint inhibitor durvalumab. In a separate, but related study, they will explore several potential drug targets identified through their BCRF research.
Breast tumors are composed of a complex variety of cell types, including cells from the immune system—concentrations of which can provide crucial information about a patient’s prognosis and the best treatment. Dr. Pusztai aims to map the immune cell composition of breast cancers and learn how the immune microenvironment changes in response to chemotherapy and immunotherapy.
Full Research Summary
Research area: To map the immune cell composition of primary breast cancer and the changes caused by immuno- and chemo- therapies.
Impact: The immune system plays an important role in the progression of primary breast cancer to metastatic breast cancer. Dr. Pusztai is conducting studies to assess the immune cell composition of primary and metastatic breast cancer to examine the changes that chemotherapy causes in the cancer genome and tumor immune environment. Identifying and understanding the mechanisms of immunosuppression and immune evasion will provide the foundation for rational immunotherapy combination therapies.
Current investigation: He and his colleagues have been focused on the collection and analysis of tissues obtained from patients with triple negative breast cancer (TNBC) participating in a clinical trial that tested the combination of immune checkpoint therapy with chemotherapy in the neoadjuvant (preoperative) setting. In addition, they are exploring novel therapeutic targets including aberrantly expressed metabolic enzymes and developing new antibody drug conjugates.
What he’s learned so far: He and his colleagues have shown that metastatic breast cancers evade immune surveillance through multiple mechanisms. These findings will inform rational combination approaches to improve response to immunotherapy in breast cancer.
What’s next: They will continue analysis of patient tissue and determine the effectiveness of durvalumab in combination with chemotherapy and identify changes in the cancer genome and immune environment that were caused by treatment. In a separate study, they will continue their ongoing work in drug development and moving their targeted agent closer to clinical development.
Dr Pusztai is Professor of Medicine at Yale University and Chief of the Breast Medical Oncology Section at the Yale Cancer Center. He is also Co-Director of the Cancer Center Genomics and Genetics Program. Dr. Pusztai received his medical degree from the Semmelweis University of Medicine in Budapest, and his D.Phil. degree from the University of Oxford in England. His research group has made important contributions to establish that estrogen receptor-positive and-negative breast cancers have fundamentally different molecular, clinical and epidemiological risk characteristics. He has been a pioneer in evaluating gene expression profiling as a diagnostic technology to predict chemotherapy and endocrine therapy sensitivity and have shown that different biological processes are involved in determining the prognosis and treatment response in different breast cancer subtypes. His group has also developed new bioinformatics tools to integrate information from across different data platforms in order to define the molecular pathways that are significantly disturbed in individual cancers and could provide the bases for future individualized treatment strategies. He made important contributions to clarify the clinical value of neoadjuvant chemotherapy in different breast cancer subtypes.
Dr Pusztai is also principal investigator of several clinical trials investigating new drugs and potential response markers. He has published over 200 manuscripts in high impact medical journals and is the Clinical Editor of the British Journal of Cancer, Member of the Scientific Advisory Board of the Breast Cancer Research Foundation, Member of the Breast Cancer Steering Committee of the NCI and Co-Chair of the Trans-ALTTO Committee that oversees the translational research projects of tissues collected during two larger randomized clinical trials (ALTTO and NeoALTTO). He is also Chair of the Data Safety Monitoring Committee of the OPTIMA trial.