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The SPORE in Breast Cancer

Vanderbilt-Ingram Cancer Center' s SPORE in Breast Cancer, established in 2003, is one of only five in the country, and focuses on innovative, translational research for better diagnosis, prognosis, screening, prevention and treatment of breast cancer.

Overview

The Vanderbilt-Ingram Cancer Center SPORE in Breast Cancer has established a true multidisciplinary program focused on conducting multidisciplinary, mechanism-based, translational research of the highest possible impact that will contribute meaningfully to measurable progress in breast cancer. Our investigators have expertise in cellular signaling and molecular biology, breast pathology, medical, surgical, and radiation oncology, clinical trial design, epidemiology and population studies, mass spectrometry, biostatistics, and biomedical informatics.

The Breast SPORE supports several initiatives including four scientific research projects, five cores that provide essential services to SPORE projects, a developmental research program to support pilot projects, and career development opportunities for physician-scientists in training. 

Breast SPORE Research Projects

The SPORE in Breast Cancer supports four research projects aimed at addressing basic, clinical and population research questions of importance in human breast cancer. All projects are translational and multidisciplinary and are led by co-investigators from multiple departments across the School of Medicine, with complementary basic science and translational/clinical expertise.

Project 1: Mechanisms of Resistance to Endocrine Therapy in ER+ Breast Cancer 

  • Clinical co-leader: Brent Rexer, MD, PhD
  • Basic co-leader: Carlos L. Arteaga, MD
  • Basic co-investigator: Ariella Hanker, PhD
  • Clinical co-investigator: Ingrid A. Mayer, MD, MSCI
  • Patient advocate: Janet Piper

Project 1 details

Project 2: Strategies to Improve Outcomes for Triple-Negative Breast Cancer Patients Integrating Subtype-Specific Genomic and Immune-Based Discoveries

  • Clinical co-leader: Vandana G. Abramson, MD
  • Basic co-leader: Jennifer A. Pietenpol, PhD
  • Basic co-investigators: Brian Lehmann, PhD and Alissa Weaver, MD, PhD
  • Patient advocate: Patricia [Patty] Lee)

Project 2 details

Project 3: Targeting the DNA Damage Response in Breast Cancer 

  • Clinical co-leader: Vandana Abramson, MD
  • Basic co-leader: David Cortez, PhD
  • Basic co-investigators: Violeta Serra, PhD, Kimberly Dahlman, PhD, Deborah Lannigan, PhD and Mark O’Connor, PhD
  • Patient advocate: Lynn Cargen

Project 3 details

Project 4: Targeting Antigen Presentation to Improve Immunotherapy Responses in Breast Cancer

  • Clinical co-leader: Ingrid A. Mayer, MD, MSCI
  • Basic co-leader: Justin M. Balko, PharmD, PhD
  • Basic co-investigator: Brent Ferrell, MD
  • Patient advocate: Linda Horton

Project 4 details

 

Breast SPORE Research Projects

The SPORE in Breast Cancer supports four research projects aimed at addressing basic, clinical and population research questions of importance in human breast cancer. All projects are translational and multidisciplinary and are led by co-investigators from multiple departments across the School of Medicine, with complementary basic science and translational/clinical expertise.

Learn more about our Breast SPORE research projects and cores

Mechanisms of Resistance to Endocrine Therapy in ER+ Breast Cancer 

  • Clinical co-leader: Brent Rexer, MD, PhD
  • Basic co-leader: Carlos L. Arteaga, MD
  • Basic co-investigator: Ariella Hanker, PhD
  • Clinical co-investigator: Ingrid A. Mayer, MD, MSCI
  • Patient advocate: Janet Piper

project 1 summary

Specific Aims:

Aim 1: To elucidate the mechanisms by which FGFR1 amplification confers resistance to the combination of fulvestrant and CDK4/6 inhibitors in ER+/FGFR amplified breast cancers

Aim 2: To conduct a randomized phase II trial of the ER downregulator fulvestrant plus palbociclib ± the pan-FGFR inhibitor erdafitinib in patients with ER+/FGFR-amplified metastatic breast cancer

Aim 3: To discover mechanisms of resistance to fulvestrant/palbociclib ± erdafitinib in organoids derived from tumors progressing in the clinical trial proposed in Aim 2


The Project 1 team profiled 155 HR+/HER2– early breast cancers from 143 patients treated with the aromatase inhibitor letrozole for 7-21 days before surgery (Science Translational Medicine 2017 PMC5723145). Whole-exome sequencing (WES) revealed a correlation between 8p11-12 and 11q13 gene amplifications, including FGFR1 and CCND1, respectively, and high on-treatment Ki67. Of note, FGFR1 is amplified in ~15% of early ER+ breast cancers where it is associated with early relapse following adjuvant tamoxifen therapy and poor patient outcome. Additionally, ctDNA data from patients enrolled in MONALEESA-2, the registration trial of ribociclib, a CDK4/6 inhibitor, showed that patients with FGFR1 amplification in ctDNA exhibited a progression-free survival of 10.6 months vs. 24.8 months in patients with wild-type FGFR1. Subsequent to these findings, Project 1 revealed that co-amplification of FGFR1 and CCND1 were associated with endocrine therapy and CDK4/6 inhibitor resistance, that could be reversed by treatment with FGFR1 and CDK4/6 inhibitors (Clin Cancer Res, 2017 PMID 29284706), and reported marked HR+/FGFR1-amplified patient-derived xenografts tumor regressions with fulvestrant, palbociclib (a CDK4/6 inhibitor) and erdafitinib (a pan-FGFR tyrosine kinase inhibitor) (Nat Commun, 2019 PMID 30914635). Based on the above preclinical data, in 2016, Dr. Mayer successfully competed for funding of a three-year Pfizer ASPIRE Breast Cancer Research Award entitled “Phase Ib trial of fulvestrant, palbociclib and erdafitinib in HR+/HER2–/FGFR-amplified metastatic breast cancer,” which now funds one of the highly translational, multi-institutional trials that will test the hypothesis that FGFR inhibitors should be tested in combination with ER antagonists and CDK4/6 inhibitors in patients with HR+/FGFR amplified breast cancer.


Featured Publications 

Jovanović B, Mayer IA, Mayer EL, Abramson VG, Bardia A, Sanders ME, Kuba MG, Estrada MV, Beeler JS, Shaver TM, Johnson KC, Sanchez V, Rosenbluth JM, Dillon PM, Forero-Torres A, Chang JC, Meszoely IM, Grau AM, Lehmann BD, Shyr Y, Sheng Q, Chen SC, Arteaga CL, Pietenpol JA. A Randomized Phase II Neoadjuvant Study of Cisplatin, Paclitaxel With or Without Everolimus in Patients with Stage II/III Triple-Negative Breast Cancer (TNBC): Responses and Long-term Outcome Correlated with Increased Frequency of DNA Damage Response Gene Mutations, TNBC Subtype, AR Status, and Ki67. Clin Cancer Res. 2017 Aug 1;23(15):4035-4045. doi: 10.1158/1078-0432.CCR-16-3055. Epub 2017 Mar 7. PubMed PMID: 28270498; PubMed Central PMCID: PMC5540799.

Lehmann BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr Y, Moses HL, Sanders ME, Pietenpol JA. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLoS One. 2016 Jun 16;11(6):e0157368. doi: 10.1371/journal.pone.0157368. eCollection 2016. PubMed PMID: 27310713; PubMed Central PMCID: PMC4911051.

Shaver TM, Lehmann BD, Beeler JS, Li CI, Li Z, Jin H, Stricker TP, Shyr Y, Pietenpol JA. Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies. Cancer Res. 2016 Aug 15;76(16):4850-60. doi: 10.1158/0008-5472.CAN-16-0058. Epub 2016 May 26. PubMed PMID: 27231203; PubMed Central PMCID: PMC4987189.

Strategies to improve outcomes for triple negative breast cancer patients involving subtype-specific targeted therapies and genomic discovery

  • Jennifer Pietenpol, PhD., Project Leader
  • Vandana Abramson, MD, Project Co-Leader

Project 1 details

Mcl-1 inhibitors for the treatment of breast cancer

  • Rebecca Cook, PhD, Project Co-Leader
  • Stephen Fesik, PhD, Project Co-Leader
  • Melinda Sanders, MD, Project Co-Leader

The obesity-metabolic biomarker axis and breast cancer risk

  • William Blot, PhD, Project Co-Leader
  • Loren Lipworth, ScD, Project Co-Leader
  • Wei Zheng, MD, PhD, Project Co-Leader

Developmental Research

The Developmental Research Program (DRP) supports pilot projects that allow early, high-risk research to move solid basic science findings toward clinical application, as well as the migration of provocative clinical observations back to the laboratory in order to understand their mechanistic basis.

The main criteria for selection and funding of developmental (pilot) projects include scientific merit, relevance to mammary biology and/or breast cancer, collaboration and potential for extramural peer-reviewed funding. There also is an emphasis on utilization of emerging technologies and on young investigators.

The aims of this program are: 

  • To support junior and established investigators conducting high-risk, innovative research applicable to breast cancer
  • To support mechanistic investigation in the laboratory of provocative clinical observations
  • To support progression of DRP projects to extramural funding and peer-reviewed publications
  • To focus on emerging technologies and approaches applicable to translational research in breast cancer

Learn more about our Breast SPORE Funding Opportunities as well as funding through other programs. 


Career Development

Improving the quantity and quality of opportunities for training in translational research is of vital importance for the success of the Breast SPORE as well as for the successful application of progress made in the laboratory to our ultimate goal: a reduction in the incidence, morbidity and mortality resulting from breast cancer. 

The Career Development Program achieves these goals by: 

  • The recruitment, support and development of young physician-scientists and laboratory-based translational/clinical investigators (MD and MD/PhD) into breast cancer research
  • The recruitment, support and development of young basic scientists (PhD) into mechanism-based applied research in breast cancer
  • Recruiting outstanding basic scientists into breast cancer research and providing clinical and translational expertise to this research
  • Providing translational research mentorship, training, and opportunities for investigators to develop the knowledge, skills and expertise to successfully pursue independent, extramurally-funded scholarly careers focused in translational research in breast cancer
  • Recruiting women and underrepresented minority investigators into research in breast cancer

Featured Publications

Research Advocacy

Since 2004, research advocates have been an integral part of the Breast SPORE team, offering patient experiences and perspectives into all aspects of breast cancer research at Vanderbilt-Ingram. These passionate, determined and dedicated volunteers are actively involved helping to bring the best science to those who are affected by breast cancer by contributing in the following ways:

  • Attend monthly Breast Cancer Programs and SPORE seminars
  • Serve on SPORE executive committee
  • Attend project meetings as part of the interdisciplinary team and participate in research discussions
  • Review and provide input on research development, design, clinical trials and informed consents
  • Develop patient-oriented resources and tools for SPORE clinical trials
  • Raise awareness through presentations to patient and community groups
  • Facilitate collaborations with local, regional, and national organizations dedicated to breast cancer
  • Participate in on-going advocate educational sessions

    Contact the Breast SPORE Team

    Breast SPORE News

    August 31, 2019

    Grant strengthens breast cancer research efforts

    Breast cancer researchers at Vanderbilt-Ingram Cancer Center have secured a fourth round of continuous Specialized Program of Research Excellence funding.
    July 19, 2019

    A critical factor for wound healing

    Vanderbilt-Ingram Cancer Center scientists have discovered a role for a tumor suppressor protein in skin wound healing.
    December 14, 2018

    Breast cancer-killing RIG

    A recent study in the journal Cancer Research demonstrates that a RIG-I agonist has potent immunogenic and therapeutic effects in breast cancer.