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

Inflammatory Breast Cancer

- Unique genomic alterations that lead to inflammatory phenotypes
- New models of inflammatory Breast Cancer

Program Leader

Justin M. Balko, Pharm.D., Ph.D.

Program Leader

Vandana G. Abramson, M.D.

All Program Members

Featured Publications

Weight Cycling Induces Innate Immune Memory in Adipose Tissue Macrophages.

Caslin, H.L., Cottam, M.A., Piñon, J.M., Boney, L.Y. & Hasty, A.H. (BC).

Front Immunol 13:984859, 2023; PMC9876596.

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Randomized Phase II Trial of Endocrine Therapy with or without Ribociclib After Progression on Cyclin-Dependent Kinase 4/6 Inhibition in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: MAINTAIN Trial.

Kalinsky, K., Accordino, M.K., Chiuzan, C., Mundi, P.S., Sakach, E., Sathe, C., Ahn, H., Trivedi, M.S., Novik, Y., Tiersten, A., Raptis, G., Baer, L.N., Oh, S.Y., Zelnak, A.B., Wisinski, K.B., Andreopoulou, E., Gradishar, W.J., Stringer-Reasor, E., Reid, S.A. (BC), O'Dea, A., O'Regan, R., Crew, K.D. & Hershman, D.L.

J Clin Oncol :JCO2202392, 2023; PMID:37207300.

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Single-Cell Analysis of Somatic Mutation Burden in Mammary Epithelial Cells of Pathogenic BRCA1/2 Mutation Carriers.

Sun, S., Brazhnik, K., Lee, M., Maslov, A.Y., Zhang, Y., Huang, Z., Klugman, S., Park, B.H. (BC), Vijg, J. & Montagna, C.

J Clin Invest 2022; PMID:35025760.

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Hotspot ESR1 Mutations are Multimodal and Contextual Modulators of Breast Cancer Metastasis.

Li, Z., Wu, Y., Yates, M.E., Tasdemir, N., Bahreini, A., Chen, J., Levine, K.M., Priedigkeit, N.M., Nasrazadani, A., Ali, S., Buluwela, L., Arnesen, S., Gertz, J., Richer, J.K., Troness, B., El-Ashry, D., Zhang, Q., Gerratana, L., Zhang, Y., Cristofanilli, M., Montanez, M.A., Sundd, P., Wallace, C.T., Watkins, S.C., Fumagalli, C., Guerini-Rocco, E., Zhu, L., Tseng, G.C., Wagle, N., Carroll, J.S., Jank, P., Denkert, C., Karsten, M.M., Blohmer, J.U., Park, B.H. (BC), Lucas, P.C., Atkinson, J.M., Lee, A.V. & Oesterreich, S.

Cancer Res 2022; PMID:35078818.

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Immune-Checkpoint Inhibitors: Long-Term Implications of Toxicity.

Johnson, D.B. (TR), Nebhan, C.A., Moslehi, J.J. & Balko, J.M. (BC).

Nat Rev Clin Oncol 2022; PMC8790946.

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An Overview of Genetic Services Delivery for Hereditary Breast Cancer.

Reid, S. (BC), Spalluto, L.B. (CO), Lang, K., Weidner, A. & Pal, T. (BC).

Breast Cancer Res Treat 2022; PMC8789372.

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Cardiac Outcomes of Subjects on Adjuvant Trastuzumab Emtansine vs Paclitaxel in Combination with Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT) Study (TBCRC033): a Randomized Controlled Trial.

Barroso-Sousa, R., Tarantino, P., Tayob, N., Dang, C., Yardley, D.A., Isakoff, S.J., Valero, V., Faggen, M., Mulvey, T., Bose, R., Hu, J., Weckstein, D., Wolff, A.C., Reeder-Hayes, K., Rugo, H.S., Ramaswamy, B., Zuckerman, D., Hart, L., Gadi, V.K., Constantine, M., Cheng, K., Briccetti, F., Schneider, B., Garrett, A.M., Marcom, K., Albain, K., DeFusco, P., Tung, N., Ardman, B., Nanda, R., Jankowitz, R.C., Rimawi, M., Abramson, V. (BC), Pohlmann, P.R., Van Poznak, C., Forero-Torres, A., Liu, M., Ruddy, K.J., Zheng, Y., Rosenberg, S.M., Gelber, R.D., Trippa, L., Barry, W., DeMeo, M., Burstein, H., Partridge, A., Winer, E.P., Krop, I. & Tolaney, S.M.

NPJ Breast Cancer 8(1):18, 2022; PMID:35173164.

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Reduced Expression of Annexin a6 Induces Metabolic Reprogramming that Favors Rapid Fatty Acid Oxidation in Triple-Negative Breast Cancer Cells.

Williams, S.D. & Sakwe, A.M. (BC).

Cancers (Basel) 14(5), 2022; PMID:35267416.

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Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response.

Taylor, B.C. & Balko, J.M. (BC).

Front Immunol 13:844866, 2022; PMC8920040.

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Phase 1b Study of Berzosertib and Cisplatin in Patients with Advanced Triple-Negative Breast Cancer.

Telli, M.L., Tolaney, S.M., Shapiro, G.I., Middleton, M., Lord, S.R., Arkenau, H.T., Tutt, A., Abramson, V. (BC), Dean, E., Haddad, T.C., Wesolowski, R., Ferrer-Playan, J., Goddemeier, T., Grombacher, T., Dong, J., Fleuranceau-Morel, P., Diaz-Padilla, I. & Plummer, R.

NPJ Breast Cancer 8(1):45, 2022; PMID:35393425.

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Peripheral Blood Monocyte Abundance Predicts Outcomes in Patients with Breast Cancer.

Axelrod, M.L., Wang, Y., Xu, Y., Sun, X., Bejan, C.A., Gonzalez-Ericsson, P.I., Nunnery, S., Bergman, R.E., Donaldson, J. (BC), Guerrero-Zotano, A.L., Massa, C., Seliger, B., Sanders, M. (BC), Mayer, I.A. & Balko, J.M. (BC).

Cancer Res Commun 2(5):286-292, 2022; PMC9604512.

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Epigenetic Repression of STING by MYC Promotes Immune Evasion and Resistance to Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer.

Lee, K.M., Lin, C.C., Servetto, A., Bae, J., Kandagatla, V., Ye, D., Kim, G., Sudhan, D.R., Mendiratta, S., González Ericsson, P.I., Balko, J.M. (BC), Lee, J., Barnes, S., Malladi, V.S., Tabrizi, S., Reddy, S.M., Yum, S., Chang, C.W., Hutchinson, K.E., Yost, S.E., Yuan, Y., Chen, Z.J., Fu, Y.X., Hanker, A.B. & Arteaga, C.L.

Cancer Immunol Res 10(7):829, 2022; PMC9250627.

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Effect of Metformin vs Placebo on Invasive Disease-Free Survival in Patients with Breast Cancer: the MA.32 Randomized Clinical Trial.

Goodwin, P.J., Chen, B.E., Gelmon, K.A., Whelan, T.J., Ennis, M., Lemieux, J., Ligibel, J.A., Hershman, D.L., Mayer, I.A., Hobday, T.J., Bliss, J.M., Rastogi, P., Rabaglio-Poretti, M., Mukherjee, S.D., Mackey, J.R., Abramson, V.G. (BC), Oja, C., Wesolowski, R., Thompson, A.M., Rea, D.W., Stos, P.M., Shepherd, L.E., Stambolic, V. & Parulekar, W.R.

JAMA 327(20):1963-1973, 2022; PMID:35608580.

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Multiomics Reveals Persistence of Obesity-Associated Immune Cell Phenotypes in Adipose Tissue During Weight Loss and Weight Regain in Mice.

Cottam, M.A., Caslin, H.L., Winn, N.C. & Hasty, A.H. (BC).

Nat Commun 13(1):2950, 2022; PMID:35618862.

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Liquid Biopsy Assessment of Circulating Tumor Cell PD-L1 and IRF-1 Expression in Patients With Advanced Solid Tumors Receiving Immune Checkpoint Inhibitor.

Kennedy, L.C. (BC), Lu, J., Kuehn, S., Ramirez, A.B., Lo, E., Sun, Y., U'Ren, L., Chow, L.Q.M., Chen, Z., Grivas, P., Kaldjian, E.P. & Gadi, V.K.

Target Oncol 2022; PMID:35696014.

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Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update.

Henry, N.L., Somerfield, M.R., Dayao, Z., Elias, A., Kalinsky, K., McShane, L.M., Moy, B., Park, B.H. (BC), Shanahan, K.M., Sharma, P., Shatsky, R., Stringer-Reasor, E., Telli, M., Turner, N.C. & DeMichele, A.

J Clin Oncol :JCO2201063, 2022; PMID:35759724.

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Call for Action: Expanding Global Access to Hereditary Cancer Genetic Testing.

Bychkovsky, B., Rana, H.Q., Ademuyiwa, F., Plichta, J., Anderson, K., Nogueira-Rodrigues, A., Santa-Maria, C.A., Coffman, L.G., Marquez, C., Das, A., Taghian, A., Koeller, D.R., Sandoval, R.L., Park, B.H. (BC) & Dizon, D.S.

Lancet Oncol 23(9):1124-1126, 2022; PMID:36055301.

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Receipt of Bilateral Mastectomy Among Women with Hereditary Breast Cancer.

Reid, S. (BC), Roberson, M.L. (CO), Koehler, K., Shah, T., Weidner, A., Whisenant, J.G. & Pal, T. (BC).

JAMA Oncol 2022; PMID:36326735.

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T Cells Specific for α-myosin Drive Immunotherapy-Related Myocarditis.

Axelrod, M.L., Meijers, W.C., Screever, E.M., Qin, J., Carroll, M.G., Sun, X., Tannous, E., Zhang, Y., Sugiura, A., Taylor, B.C., Hanna, A., Zhang, S., Amancherla, K., Tai, W., Wright, J.J., Wei, S.C., Opalenik, S.R., Toren, A.L., Rathmell, J.C. (HT), Ferrell, P.B. (TR), Phillips, E.J., Mallal, S. (ZY), Johnson, D.B. (TR), Allison, J.P., Moslehi, J.J. & Balko, J.M. (BC).

Nature 2022; PMID:36385524.

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Obesity and Metabolic Syndrome are Associated with Short-Term Endocrine Therapy Resistance in Early ER + Breast Cancer.

Bergman, R., Berko, Y.A., Sanchez, V., Sanders, M.E. (BC), Gonzalez-Ericsson, P.I., Arteaga, C.L. & Rexer, B.N. (BC).

Breast Cancer Res Treat 2022; PMID:36396775.

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Tucatinib vs Placebo, Both in Combination with Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients with Brain Metastases: Updated Exploratory Analysis of the HER2CLIMB Randomized Clinical Trial.

Lin, N.U., Murthy, R.K., Abramson, V. (BC), Anders, C., Bachelot, T., Bedard, P.L., Borges, V., Cameron, D., Carey, L.A., Chien, A.J., Curigliano, G., DiGiovanna, M.P., Gelmon, K., Hortobagyi, G., Hurvitz, S.A., Krop, I., Loi, S., Loibl, S., Mueller, V., Oliveira, M., Paplomata, E., Pegram, M., Slamon, D., Zelnak, A., Ramos, J., Feng, W. & Winer, E.

JAMA Oncol 2022; PMID:36454580.

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Using the HER2/CEP17 FISH Ratio to Predict Pathologic Complete Response Following Neoadjuvant Anti-HER2 Doublet Therapy in HER2+ Breast Cancer.

Lander, E.M., Rappazzo, K.C., Huang, L.C., Hu, J.R., Chen, H., Shyr, Y. (ZY) & Abramson, V.G. (BC).

Oncologist 2022; PMID:36495309.

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Multiomics in Primary and Metastatic Breast Tumors from the AURORA US Network Finds Microenvironment and Epigenetic Drivers of Metastasis.

Garcia-Recio, S., Hinoue, T., Wheeler, G.L., Kelly, B.J., Garrido-Castro, A.C., Pascual, T., De Cubas, A.A., Xia, Y., Felsheim, B.M., McClure, M.B., Rajkovic, A., Karaesmen, E., Smith, M.A., Fan, C., Ericsson, P.I.G., Sanders, M.E. (BC), Creighton, C.J., Bowen, J., Leraas, K., Burns, R.T., Coppens, S., Wheless, A., Rezk, S., Garrett, A.L., Parker, J.S., Foy, K.K., Shen, H., Park, B.H. (BC), Krop, I., Anders, C., Gastier-Foster, J., Rimawi, M.F., Nanda, R., Lin, N.U., Isaacs, C., Marcom, P.K., Storniolo, A.M., Couch, F.J., Chandran, U., Davis, M., Silverstein, J., Ropelewski, A., Liu, M.C., Hilsenbeck, S.G., Norton, L., Richardson, A.L., Symmans, W.F., Wolff, A.C., Davidson, N.E., Carey, L.A., Lee, A.V., Balko, J.M. (BC), Hoadley, K.A., Laird, P.W., Mardis, E.R., King, T.A. & Perou, C.M.

Nat Cancer 2022; PMID:36585450.

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Program News

August 10, 2023

New leaders named to Vanderbilt-Ingram research programs

Seven new leaders have been appointed to guide Vanderbilt-Ingram Cancer Center's research programs.

December 15, 2023

Clinical trial shows efficacy for atezolizumab combined with carboplatin

Immunotherapy in combination with chemotherapy has become an important therapeutic treatment option in some patients with metastatic breast cancer. Which patients will benefit the most, however, remains unclear; current biomarkers such as PD-L1 that are used to predict response are mediocre at best.

March 7, 2023

Nicole Kidman and Keith Urban gift supports breast cancer clinical trials at Vanderbilt-Ingram Cancer Center

Nicole Kidman and Keith Urban have made a generous financial gift to Vanderbilt-Ingram Cancer Center in support of clinical trials for new and better therapies for breast cancer.

More Program News