Silvia Formenti, MD

2008-2009 BCRF Project:
(made possible by generous support from Coach)
Co-Investigator: Robert J. Schneider, PhD, NYU School of Medicine, New York

A unique understanding of the genetic and molecular characteristics of locally advanced breast cancer (LABC) has emerged from an international multi-ethnic study funded by BCRF, conducted by Drs. Formenti and Schneider. Their research has disclosed the importance of the mTOR/4E-BP1 biochemical pathway and its control of tumor protein synthesis in LABC and inflammatory breast cancer (IBC). These findings have led to the development of new approaches for the treatment of LABC and the ongoing development of a new drug to inhibit breast tumor angiogenesis. The researchers have established the critical and under-explored importance of translational control by the mTOR/4E-BP1 pathway in LABC and IBC, and they are identifying a genetic subtype of LABC that may correspond to increased treatment response.

In the coming year, the investigators will exploit these findings to complete preclinical development of a new approach for the treatment of LABC to support a new clinical trial. Specifically, they will utilize the vascular normalization theory to develop a new therapeutic approach for the treatment of LABC that incorporates the inhibition of the mTOR/4E-BP1 pathway through use of the drug rapamycin. Preclinical modeling of mechanisms and optimal sequencing are ongoing and will be completed in this next year of research. These results will generate the data necessary to inform a clinical protocol for LABC. In parallel, the investigators will continue to accrue patients internationally to their tissue and clinical data bank for LABC. This bank represents a unique asset to enable investigators to explore the role of racial and ethnic (genetic) differences in the presentation and treatment of LABC.

Bio:
Silvia Formenti, M.D., was appointed in 2000 as the first Sandra and Edward H. Meyer Chairman of the new Department of Radiation Oncology. Widely respected for her work in breast and cervical cancer, Dr. Formenti joined NYU from the University of Southern California, Keck School of Medicine in Los Angeles, where she was a tenured Associate Professor of both Radiation Oncology and Medicine. She has been a member of the Advisory Board to the NYU Breast Cancer Program since 1996.

Dr. Formenti, a native of Milan, Italy, attended medical school at the Universita degli Studi di Milano. She completed residencies in internal medicine and medical oncology followed by one in radiology and radiation oncology in Milan, before coming to the States to work at USC in Dr. Malcolm Mitchell's laboratory, funded by a grant from the Italian National Research Committee (CNR). After a year in the lab she returned to the clinic as an Audrey Meyer Mars American Cancer Society Fellow and worked with Dr. Robert Lukes and Dr. Alexandra Levine on AIDS and Lymphomas. She then elected to permanently transfer to this country and completed an internship in general medicine and a residency in radiation oncology, before joining the faculty at USC.

A prolific researcher, Dr. Formenti started with a 3-year ACS career development award and is currently principal or co-principal investigator on five multi-year peer-reviewed grants with more than $ 3 million in total funding. She has devoted her research career to the study of women's malignancies, with a particular focus on underserved patients and Latina women. She has pioneered the use of concurrent chemo-radiation in the neo-adjuvant (before surgery) setting of LABC, an ideal setting to explore associations of pre-treatment tumor molecular markers with the extent of pathological response (response in the removed surgical specimen) after chemo-radiation. This research has been consistently funded by the NIH and ACS. The translational component of this research consists of several collaborations with basic scientists to identify in the laboratory which original tumor molecular tumor marker might determine response to a specific treatment. In addition, at NYU, in collaboration with Dr. Sandra Demaria she is studying how chemo-radiation induced cell-death affects patient's immunity.

Finally, funded by a grant from the Department of Defense, she is studying the role of partial breast radiation with an accelerated regimen, 5 instead of 30 fractions. She is also the P.I. in two other studies investigating the role of intensity modulated radiation therapy (IMRT) as a tool to reduce the number of radiation sessions required to treat small breast cancers.

In addition to her role as Chairman of the NYU Department of Radiation Oncology, Dr. Formenti is currently the Associate Director for Clinical Research as well as the Leader of the Breast Cancer Research Program of the NYU Cancer Institute, where she oversees the clinical and research efforts of over 30 investigators.