Breast Cancer Research Program

The Breast Cancer Research Program has the overarching goal of addressing unmet clinical needs by translating basic science discoveries into practice-changing clinical research. The program also fosters new translational directions by catalyzing laboratory and population-based research that could positively impact reduction of mortality and health disparities, as well as improvement of optimal care in breast cancer. This "bedside to bench and back" approach is achieved through a strong cadre of researchers including laboratory, clinical and population-based investigators, as well as extensive scientific collaborations with multiple national and international institutions, as well as consortia and pharma. Ongoing basic and translational discoveries from the Breast Cancer Research Program and other programs provide a steady pipeline for novel interventional trials with innovative approaches. Through these research endeavors, the Breast Cancer Research Program also provides training opportunities for mentoring the next generation of breast cancer researchers.

RESEARCH THEMES

The Breast Cancer Program has expertise in and leads clinical trials related to:

ER-Positive Breast Cancer

-Inhibition of phosphatidylinositol-3 kinase (PI3K) as a strategy to abrogate antiestrogen resistance in HR+ breast cancer
-FGFR pathway as a strategy to abrogate CDK4/6 inhibition and antiestrogen resistance in HR+ breast cancer
-RSK2 as a regulator and therapeutic target for HR+ breast cancer
-CDK4/6 inhibitors, anti-tumor immunity and the pro-inflammatory secretome

Triple-Negative Breast Cancer

-Refinement of triple-negative breast cancer (TNBC) molecular subtypes: Implications for neoadjuvant chemotherapy selection
-JAK2 amplification as a prognostic and predictive biomarker in TNBC
-Strategies to improve outcomes for TNBC patients integrating subtype-specific genomic and immune-based discoveries

Immunotherapy in Breast Cancer

-Targeting antigen presentation to improve immunotherapy responses in breast cancer
-Mutant spliceosomes as a predictor for immune checkpoint blockade therapies

Non-Invasive Imaging in Breast Cancer

-Image integration to breast cancer biology and clinical trials
-Evaluating non-invasive imaging technologies to predict anti-cancer drug action and treatment response

DNA damage in Breast Cancer

-Targeting the DNA damage response and resistance in breast cancer

Tumor dormancy

-Identifying mechanisms of tumor dormancy in the bone marrow

Disparities & Optimization of Care Delivery

-Breast cancer in blacks: impact on genomics, healthcare use and lifestyle on outcomes (BRIGHT)
-Southern Community Cohort Study (SCCS): Relationship between obesity and breast cancer
-Optimization of care delivery in breast cancer, focusing on novel methods for dissemination of new data and cutting-edge technologies, as well as implementation of recent guidelines and approved therapies for breast cancer

Precision Oncology Initiative

-Electronic health record (EHR) decision support for genetic testing to inform clinical management, including eligibility and enrollment on clinical trials
-Molecular tumor board to evaluate CLIA-grade reports for actionability and make recommendations based on current knowledge and available clinical trials
-Structural Biology Precision Medicine Working Group

Targeted Therapies

-Ongoing basic and translational discoveries provide a steady pipeline for novel interventional trials with innovative approaches.
-Systematic liquid biopsy using cell-free DNA (cfDNA) and tissue repository protocol for all stages and types of breast cancer
-Extensive scientific collaborations with multiple national and international institutions, as well as consortia and pharma

Program Leader

Ingrid A. Mayer, M.D., M.S.C.I.

Program Leader

Ben Park, M.D., Ph.D.

All Program Members

Featured Publications

Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer.

Sparano, J.A., Gray, R.J., Ravdin, P.M., Makower, D.F., Pritchard, K.I., Albain, K.S., Hayes, D.F., Geyer, C.E., Dees, E.C., Goetz, M.P., Olson, J.A., Lively, T., Badve, S.S., Saphner, T.J., Wagner, L.I., Whelan, T.J., Ellis, M.J., Paik, S., Wood, W.C., Keane, M.M., Gomez Moreno, H.L., Reddy, P.S., Goggins, T.F., Mayer, I.A. (BC), Brufsky, A.M., Toppmeyer, D.L., Kaklamani, V.G., Berenberg, J.L., Abrams, J. & Sledge, G.W.

N Engl J Med 380(25):2395-2405, 2019; PMC6709671.

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A Critical Need for Better Cancer Immunotherapy Models: Are Organotypic Tumor Spheroid Cultures the Answer?

Balko JM (BC), Sosman JA.

Cancer Discov 2018 FEB 8(2):143-145 PMID:29431673.

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MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation

Lee KM, Giltnane JM, Balko JM (BC), Schwarz LJ, Guerrero-Zotano AL, Hutchinson KE, Nixon MJ, Estrada MV, Sánchez V, Sanders M (BC), Lee T, Gómez H, Lluch A, Pérez-Fidalgo JA, Wolf MM, Andrejeva G, Rathmell JC (HT), Fesik SW (ST), Arteaga CL

Cell Metab. 2017 OCT 3 26(4):633-647.e7 PMC5650077

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Genomic profiling of ER(+) breast cancers after short-term estrogen suppression reveals alterations associated with endocrine resistance

Giltnane JM, Hutchinson KE, Stricker TP (BC), Formisano L, Young CD, Estrada MV, Nixon MJ, Du L, Sanchez V, Ericsson PG, Kuba MG, Sanders M (BC), Mu XJ, Van Allen EM, Wagle N, Mayer IA (BC), Abramson VG (BC), Gόmez H, Rizzo M, Toy W, Chandarlapaty S, Mayer EL, Christiansen J, Murphy D, Fitzgerald K, Wang K, Ross JS, Miller VA, Stephens PJ, Yelensky R, Garraway L, Shyr Y (NP), Meszoely IM (BC), Balko JM (BC), Arteaga CL (BC)

Sci Transl Med 2017 AUG 9 9(402) PMC5723145

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An Acquired HER2(T798I) Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer

Hanker AB (BC), Red Brewer M, Brewer MR, Sheehan JH (BC), Koch JP, Sliwoski GR, Nagy R, Lanman R, Berger MF, Hyman DM, Solit DB, He J, Miller V, Cutler RE, Lalani AS, Cross D, Lovly CM (TR), Meiler J (TR), Arteaga CL (BC)

Cancer Discov 2017 JUN 8 7(6):575-585 PMC5457707

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Neoadjuvant Trials in ER(+) Breast Cancer: A Tool for Acceleration of Drug Development and Discovery.

Guerrero-Zotano AL, Arteaga CL (BC).

Cancer Discov 2017 JUN 7(6):561-574 PMC5497752.

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