Research & Publications
I am the Director of Breast Cancer Translational Research (https://medicine.yale.edu/lab/pusztai/people/) at Yale Cancer Center and Co-Director of the Yale Cancer Center’s Cancer Genetics, Genomics and Epigenetics Program. I am responsible for organizing, building, and leading a program of extramurally funded multidisciplinary clinical and laboratory research on breast cancer. We have developed a portfolio of innovative clinical trials and initiated several translational research projects involving laboratory and clinical scientists. My laboratory includes a “wet” lab, where we focus on developing new therapeutic strategies and drugs for triple-negative breast cancer, and a bioinformatics team that analyzes and develops new methodologies for interpreting gene expression and next-generation sequencing data. In the clinic, our goal is to “divide and conquer” by identifying molecularly defined subtypes of breast cancer and designing distinct strategies for curing each subtype. In the laboratory, our goal is to explore new paradigms in cancer biology. We investigate the functional impact of clonal heterogeneity within the same cancer, and how interactions between germline polymorphisms in regulatory kinases and somatic mutations collectively determine the malignant phenotype. We also study how the tumor immune microenvironment influences the course of the disease and if it could be exploited for treatment, we initiated and lead several ongoing immunotherapy trials in breast cancer.
Extensive Research Description
- My research group has made important contributions to establish that estrogen receptor-positive and-negative breast cancers are fundamentally different molecular and clinical entities with distinct epidemiological risk factors. We have shown that different biological processes are involved in determining the prognosis and treatment response in different types of breast cancers. We were the first to show that basal-like breast cancers have significantly higher chemotherapy sensitivity than ER positive cancers. We demonstrated the statistical pitfalls of conducting clinical trials that include both ER-positive and ER-negative breast cancer that contributed to the numerous contradictory results generated by older randomized adjuvant chemotherapy trial.
- We also played a leading role in evaluating gene expression profiling as a diagnostic technology and particularly as a potential predictive test for chemotherapy and endocrine therapy sensitivity. During this process we developed new bioinformatics algorithms to identify informative genes and novel web tools to interpret the biological consequences of the multiple genomic abnormalities detected in cancer. We conducted the first clinical trial in cancer to test several gene signatures as patient selection tools for a biologically targeted drug, dasatinib.
- My group has also made important contributions to clarifying the clinical value of preoperative chemotherapy for breast cancer and we created and important decision making tools that clinicians can use in the clinic to decide who are the most appropriate patients for neoadjuvant chemotherapy. We created a free website for physicians to calculate the probability of achieving pathologic complete response based on routine pathologic variables of the cancer (www.mdanderson.org/pcr) and introduced a new method to quantify residual cancer burden after therapy which is more accurate and versatile than any previous pathological measurement methods and is now adopted by several large clinical studies as endpoint metric.
Breast; Breast Neoplasms; Genetics; Medical Oncology; Genomics; Translational Medical Research
Public Health Interests