Skip to Main Content
Directory of Faculty Research Interests
YSM Home

INFORMATION FOR

DownloadHi-Res Photo

Lajos Pusztai, MD, DPhil

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

Contact Information

Lajos Pusztai, MD, DPhil
Breast Medical Oncology Group
Download CV

Related Links

Yale Medicine

Patient Care

Are you a patient?Please visit the Yale Medicine website for information about the services we offer and making an appointment.View Doctor Profile

Research Summary

I lead my own research laboratory (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. 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 Research, Biomedical

Public Health Interests

Cancer

Research Image

Genomic architecture of cancer

The landscape of molecular abnormalities in cancers

Selected Publications

Clinical Trials

ConditionsStudy Title
BreastAn Open-Label Phase II Trial to Evaluate the Efficacy and Safety of Neoadjuvant Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel Plus Trastuzumab and Pertuzumab in Early Stage HER2-Negative Breast Cancer Patients Selected With a Test Measuring Live Cell HER2 Signaling Transduction (FACT 1)
BreastThe CompassHER2 Trials (Comprehensive Use of Pathologic Response Assessment to Optimize Therapy in HER2-Positive Breast Cancer) CompassHER2 Residual Disease (RD), a Double-Blinded, Phase III Randomized Trial of T-DM1 Compared With T-DM1 and Tucatinib
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 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)
BreastA Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator's Choice of Chemotherapy in Patients Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION Breast02)
BreastAn observational study of circulating tumor DNA in triple negative breast cancers with residual disease after standard neoadjuvant treatment.
BreastA Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With The Physician's Choice of Endocrine Therapy Plus Everolimus in Patients With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
Edit Profile