Breast Cancer Disease Management Group Research
At Perlmutter Cancer Center, basic scientists, translational researchers, and clinicians in our Breast Cancer Disease Management Group (DMG) perform clinical and laboratory research that improves breast cancer screening, diagnosis, and treatment for women from all cultural and socioeconomic backgrounds.
Our breast cancer researchers integrate genomic and molecular biology to improve the understanding of the molecular basis for how breast cancer develops, invades, and metastasizes. Only recently has scientific evidence emerged to explain why administering surgery, radiotherapy, and chemotherapy to large groups of breast cancer patients has benefited only a relatively small patient subset. Our investigators seek new treatment solutions that benefit as many patients with breast cancer as possible while improving the safety and efficacy of radiation and systemic therapies. We achieve this by focusing on molecular subtypes and targeted approaches to treatment.
Research in our DMG has led to the development of novel therapies, including the clinical development of ribociclib, a novel CDK4-6 inhibitor approved by the U.S. Food and Drug Administration for use in combination with letrozole. We are conducting clinical trials to evaluate the use of ribociclib in combination with fulvestrant and administering ribociclib after palbociclib or ribociclib progression.
We have performed research on immunotherapy for patients with triple-negative breast cancer and HER2-positive breast cancer. Our group led national trials to evaluate the safety and efficacy of pembroluzimab in patients with metastatic triple-negative breast cancer. In HER2-positive breast cancer, we are conducting a clinical trial to determine the safety and efficacy of atezoluzimab, an anti-PDL1 monoclonal antibody, in combination with trastuzumab-DM1. We are also evaluating novel HER2 targeted therapies in patients with metastatic breast cancer (e.g., margetuximab).
Our diverse patient population, including large multiethnic, international groups comprised mostly of medically underserved and minority women with breast cancer, helps us investigate treatment solutions for a variety of women. Our unique relationship with NYC Health + Hospitals/Bellevue, part of the largest public hospital group in the United States, also enables us to study the biology and treatment of breast cancer in women from all walks of life.
Breast Cancer Research Leadership
Francisco J. Esteva, MD, PhD
Professor, Department of Medicine
Associate Director of Clinical Investigation, Perlmutter Cancer Center
Director, Breast Medical Oncology Program
Freya R. Schnabel, MD
Professor, Department of Surgery
Director of Breast Surgery
Carmen A. Perez, MD, PhD
Assistant Professor, Department of Radiation
Breast Cancer Research Areas of Focus
Our goal is to further understand the role of breast cancer genomics to personalize diagnosis, prognosis, and therapy, focusing on five key areas of breast cancer research.
Epidemiology and Prevention
Our investigators study the response, resistance, and metastasis of locally advanced breast cancer (LABC), a persistently understudied subtype that is common among medically underserved patients and a leading presentation of breast cancer worldwide. We are also researching genetic and molecular markers for targeted treatment of LABC in New York women with the goal of translating the Akt/mTOR pathway to treatment.
Our scientists study the role of polymorphisms in DNA repair pathways in breast cancer etiology and seek novel biomarkers for early detection. We investigate the inflammatory responses and oxidative stress in breast cancer development and evaluate pituitary hormones, growth hormone, and prolactin in mammary gland development and breast cancer risk. We also research the protective role of pregnancy in maternal breast and ovarian cancers and fertility after breast cancer treatment.
Investigators in our group further identify sociocultural factors that affect care-seeking behavior and treatment and look into treatment adherence issues among breast cancer patients with LABC.
Hormone Receptors and Signal Transduction
We investigate hormone receptors and signaling pathways involved in breast cancer, including nuclear hormone receptors and signal transduction and transcriptional regulation by ER, AR, and GR receptors. We are researching the differential effects of ER-interacting proteins on ER activity, circulating estrogenic molecules and breast cancer risk, and the role of IGF-1 in breast cancer development and progression. Our group also studies breast cancer chemoprevention by SOM230, an IGF-1 action inhibitor.
Invasiveness, Metastasis, and Angiogenesis: Extracellular Matrix Studies
We analyze the invasiveness, metastasis, and development of agents that inhibit angiogenesis. This includes researching latent forms of TGF-β1 and TGF-β3 and their roles in invasion and metastasis, extracellular matrix (ECM) in breast cancer invasion and metastasis, and non-proteolytic roles of proteinases in breast cancer cell proliferation and migration.
Other research areas of focus include the following:
- mammary developmental changes in breast cancer invasiveness and metastasis
- matrix remodeling in angiogenesis and breast cancer invasion
- the role of STAT3 in breast cancer progression
- kinases and ubiquitylating enzymes in breast cancer, SWI/SNF in breast cancer development
- cellular protein synthesis in breast cancer invasion and metastasis
- LABC angiogenesis and metastasis
- TGF-β1 and VEGF during angiogenesis
- translational control and the mTOR pathway in breast cancer hypoxia, tumor progression, and angiogenesis
- new biomarkers for ductal carcinoma in situ (DCIS) invasion and LABC metastasis
- cytologic characterization of breast lesion microinvasion
- lymphadenectomy application in breast cancer and melanoma
- developing a breast tissue bank
- cofactors of metastasis of large breast tumors
- development of anti-angiogenic PTC299, a specific inhibitor of VEGF mRNA translation
Immunity and Tumor Immunology
Our focus is on tumor immunology using targeted radiation therapy to induce an immune response against a breast cancer tumor. We use this therapy to enhance the effectiveness of immunotherapy, chemoradiation, and tumor immunity. We also examine STAT activation by janus kinases.
Radiobiology and Physics Research
Scientists in our area explore new approaches and uses for radiation treatment in breast cancer, expanding the biological understanding of radiation-induced fibrosis and improving the molecular understanding of radiation's effects on normal and cancerous breast tissue.
We study TGF-β1 in postradiation breast fibrosis and seek molecular and genetic markers to predict treatment response for chemoradiation and LABC. We also investigate radiation/chemotherapy resistance, TAMs, tumor response to chemoradiation, and breast tumor progression.