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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
- Seeking strategies to improve response to immunotherapy in triple negative breast cancer (TNBC).
- Clinical and laboratory studies are conducted to assess gene expression profiles of tumor cells and infiltrating immune cells to devise strategies to improve response to these therapies.
- These studies will inform the design of rational combinations of immunotherapy drugs for early stage and metastatic breast cancer.
Tumors are not one cell type, but rather are a mixture of different cell types, often including cells from blood vessels and the immune system. Dr. Pusztai is conducting studies to understand the clinical implications of this tumor complexity and the role of immune cell infiltration in breast cancer. In the last year, his group showed that high immune cell presence in tumors from newly diagnosed triple negative breast cancers (TNBC) patients predicts a better prognosis and greater sensitivity to anti-cancer drugs.
Full Research Summary
New immune therapies called checkpoint inhibitors have shown some success in triple negative breast cancers (TNBC), but most patients do not respond. In the past several years, Dr. Pusztai's team has been conducting studies to examine the interaction between the breast cancer gene mutation profile and the immune microenvironment of the tumor to devise strategies to improve response to these therapies.
In previous BCRF-supported research he and his colleagues discovered that triple negative breast tumors that contained a high concentration of immune cells had fewer genomic abnormalities. In the last year showed that high immune cell presence in the newly diagnosed triple negative breast cancers (TNBC) predicts for better prognosis, greater chemotherapy sensitivity and fewer abnormalities in the cancer genome.
To test the role of immunotherapy in early stage TNBC they have initiated two important trials NCT02489448 and NCT02954874. Their next step is to study the immune environment of metastatic cancers and design rational immunotherapy combinations for these patients.
Dr. Pusztai's team continues to analyze the breast cancer genome using the large amount of existing data and will also continue collecting breast cancer tissue samples from patients who receive neoadjuvant immune checkpoint inhibitor therapy on our ongoing clinical trial (NCT02489448).
Information obtained from this research will allow the design of rational combinations of immunotherapy drugs to treat early stage and metastatic breast cancer more effectively.
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.