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Lajos Pusztai, MD, DPhil

Professor of Medicine (Medical Oncology); Co-Leader, Genetics, Genomics and Epigenetics, Yale Cancer Center

Research Summary

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

  1. 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.
  2. 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.
  3. 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.


Coauthors

Research Interests

Breast; Breast Neoplasms; Genetics; Medical Oncology; Genomics; Translational Medical Research

Public Health Interests

Cancer

Research Image

Selected Publications

Clinical Trials

ConditionsStudy Title
BreastA Randomized Phase II Trial Of Circulating Tumor DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer
BreastRandomized Phase 2 Clinical Trial of Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab + Neoantigen Vaccine vs. Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer
BreastComparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS: A Phase III Prospective Randomized Trial
BreastA Phase I, Open-Label Study of D-0502 Single Agent and D-0502 in Combination With Palbociclib in Women With Advanced or Metastatic ER-Positive and HER2-Negative Breast Cancer
BreastA Phase 2 Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) in Patients With Pretreated Metastatic Triple Negative Breast Cancer
Breast - Female; BreastTAILOR RT: A Randomized Trial of Regional Radiotherapy in Biomarker Low Risk Node Positive Breast Cancer
Breast - Female; Breast - Male; BreastA Randomized Phase III Trial Comparing Axillary Lymph Node Dissection to Axillary Radiation in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy
Breast - Female; BreastA Randomized Phase II Study to Evaluate Efficacy of T-DM1 With or Without Palbociclib in the Treatment of Patients With Metastatic HER2 Positive Breast Cancer
BreastRandomized Non-Inferiority Trial Comparing Overall Survival of Patients Monitored With Serum Tumor Marker Directed Disease Monitoring (STMDDM) Versus Usual Care in Patients With Metastatic Hormone Receptor Positive Breast Cancer
Breast - FemaleI-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
Breast - Female; Phase IA Phase II Multiple-Arm, Open-Label, Randomized Study of PARP Inhibition (Veliparib; ABT-888) and Anti-PD-L1 Therapy (Atezolizumab; MPDL3280A) Either Alone or in Combination in Homologous DNA Repair (HDR) Deficient Triple Negative Breast Cancer (TNBC)
Anus; Bones and Joints; Brain and Nervous System; Breast - Female; Breast - Male; Colon; Corpus Uteri; Esophagus; Eye and Orbit; Hodgkin's Lymphoma; Kaposi's sarcoma; Kidney; Larynx; Lip, Oral Cavity and Pharynx; Liver; Lung; Lymphoid Leukemia; Melanoma, skin; Non-Hodgkin's Lymphoma; Other Digestive Organ; Other Endocrine System; Other Female Genital; Other Male Genital; Other Respiratory and Intrathoracic Organs; Other Skin; Other Urinary; Ovary; Pancreas; Prostate; Rectum; Small Intestine; Soft Tissue; Stomach; Thyroid; Cervix; Urinary BladderNCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors or Lymphomas
Breast - Female; Breast - MaleA Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer