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Each Project will contribute substantially to the understanding of the biology of breast cancer. The preclinical and clinical findings from these projects will stimulate further research and could have significant clinical impact.

Project 1: Androgens, androgen receptor signaling and breast carcinogenesis

Project Co-Leaders: Myles Brown, MD (DFCI) and Rulla Tamimi, ScD (BWH)

Co-Investigators: Stuart Schnitt, MD (BIDMC); Aditi Hazra, PhD (BWH); Meredith Regan, ScD (DFCI); Elgene Lim, MD, PhD (DFCI)

Patient Advocate: Carol Matyka and Marie Artis Levine

Project 1 brings together strong basic- and population-science investigators. It builds upon promising clues about androgen receptor (AR) signaling and will investigate the role of signaling through the AR and the development and progression of breast cancer. The investigators will develop a novel approach to characterizing AR signaling as part of this effort.


Project 2: Overcoming Resistance to HER2-Directed Therapies for Breast Cancer

Project Co-Leaders: Thomas Roberts, PhD (DFCI) and Ian Krop, MD, PhD (DFCI)

Co-Investigators: Jean Zhao, PhD (DFCI); Nancy Lin, MD (DFCI); Eric Winer, MD (DFCI); Nikhil Wagle, MD (DFCI, Broad Institute)

Site Investigators: Dejan Juric, MD, PhD (MGH); Ingrid Mayer, MD (Vanderbilt Ingram Cancer Center); Carey Anders, MD (UNC Lineberger Comprehensive Cancer Center); Anna Maria Storniolo (Indiana University)

Patient Advocates: Elizabeth Frank and Paulette Cournoyer

Collaborator: Laura Collins, MD (BIDMC)

Project 2 uses state-of-the-art genetically engineered mouse models and a cutting edge clinical trial to evaluate resistance mechanisms in HER2+ breast cancer. It seeks to overcome this resistance by further interrogating the PI3 kinase pathway, and will evaluate sensitivity and resistance to PI3 kinase inhibitors.


Project 3: Novel Strategies to Extend DNA Repair Therapies for Triple Negative Breast Cancer

Project Co-Leaders: Alan D’Andrea, MD (DFCI) and Judy Garber, MD, MPH (DFCI)

Co-Investigators: Erica Mayer, MD, MPH (DFCI); Andrea Richardson, MD, PhD (DFCI); Geoffrey Shapiro, MD, PhD (DFCI); Elgene Lim, MD, PhD (DFCI); Scott Rodig, MD (BWH); William Barry, PhD (DFCI); Julie Najita, PhD (DFCI); Jeff Supko, MD (MGH); Steven Isakoff, MD, PhD (MGH); Nadine Tung, MD (BIDMC)

Patient Advocates: Barbara LeStage and Sara Weiss

Project 3 shifts current paradigms by the development of approaches that will sensitize BRCA-proficient triple negative breast cancer cells to PARP inhibition. The Project is built upon a solid background including cell lines, patient-derived orthotopic xenograft models, and early phase clinical trials.


Project 4: BET bromodomain proteins as novel therapeutic targets in triple negative breast cancer

Project Co-Leaders: Kornelia Polyak, MD, PhD (DFCI) and Eric Winer, MD (DFCI)

Co-Investigators: William Barry, PhD (DFCI); James Bradner, MD (DFCI)Jane Brock, MD (BWH); Lisa Carey, MD (UNC); Steven Isakoff, MD, PhD (MGH); Daniel Silver, MD, PhD (DFCI)

Patient Advocate: Ruth Fax and Penny Blaisdell

Project 4 explores a “new avenue” in drug development assessing the mechanisms of action of BET/bromodomain inhibitors for the treatment of triple negative breast cancer. A strong pre-clinical phase is followed by a clinical trial with ability to understand how genomic modulation impacts the outcome of patients diagnosed with triple negative breast cancer.