This second renewal application of the Mayo Clinic Breast Cancer SPORE is being submitted with the vision that the burden of breast cancer can be reduced through the performance of innovative translational research addressing issues of high significance for women. The science of the SPORE includes four translational research projects. Project 1: ?Cancer risks for mutations in breast cancer predisposition genes? focuses on non-BRCA1/BRCA2 genes included in ?panel based? tests. Using the PROMPT registry, the investigators will define the penetrance of breast cancers associated with inactivating mutations, the clinical relevance of variants of uncertain significance, and pathological ?phenotype? of these mutations. Project 2: ?Therapeutic targeting of ER? in triple negative breast cancer (TNBC)? is based on Mayo investigator data that ER?, when expressed in TNBC, is prognostic, and that ER? agonists suppress proliferation through the TGF? pathway. This project culminates in a phase II study of estradiol in ER?+TNBC within the Translational Breast Cancer Research Symposium. Project 3: ?Measles virus based immunovirotherapy in the treatment of metastatic breast cancer? is based on pioneering work of Mayo investigators to develop a measles virus (MV) that expresses an immunostimulatory transgene (MV-NAP), and the synergistic antitumor activity of MV-NAP with PD-1 blockade. This project includes a MV-NAP phase I study, and development of additional preclinical data that will inform the clinical trial of the combination of MV-NAP and PD-1 blockade. Project 4: ?Pharmacogenomics of aromatase inhibitors (AI) in early stage postmenopausal breast cancer? is based upon the importance of estrogen levels in AI-treated women. The investigators plan secondary analyses of adjuvant AI trials to determine whether inadequate estrogen suppression is associated with cancer recurrence, followed by a genome-wide analysis to identify genetic variants associated with the ?optimal? estrogen threshold and then prospective validation in a clinical study. These research projects are supported by three highly interactive cores: Core A: Administrative Core, Core B: Biospecimen and Pathology Core, and Core C: Biostatistics, Bioinformatics, and Patient Registry Core. A Developmental Research Program will continue to identify and develop research projects that hold the greatest promise to advance to full SPORE projects, and a Career Enhancement Program will continue to identify and support faculty investigators in breast cancer translational research that have the greatest potential to become future SPORE leaders. The investigators, cores, and the research programs in the SPORE are all integrated in the Mayo Clinic Cancer Center. Collectively, our SPORE will make discoveries and translate them into the clinic for the benefit of women with, or at risk of breast cancer.

Public Health Relevance

The Mayo Clinic Breast Cancer SPORE addresses significant problems relating to breast cancer with the goal of reducing morbidity and mortality from the disease. This will be accomplished through projects focusing on breast cancer risk, novel ways to target and treat chemotherapy-resistant disease, and pharmacogenomics of the host genome in women receiving adjuvant aromatase inhibitors. The proposed research addresses vitally important issues to an enormous number of women both with, and at risk of, developing breast cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Courtney, Joyann
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mayo Clinic, Rochester
United States
Zip Code
Ho, Ming-Fen; Lummertz da Rocha, Edroaldo; Zhang, Cheng et al. (2018) TCL1A, a Novel Transcription Factor and a Coregulator of Nuclear Factor ?B p65: Single Nucleotide Polymorphism and Estrogen Dependence. J Pharmacol Exp Ther 365:700-710
Horne, Hisani N; Oh, Hannah; Sherman, Mark E et al. (2018) E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium. Sci Rep 8:6574
Reese, Jordan M; Bruinsma, Elizabeth S; Nelson, Adam W et al. (2018) ER?-mediated induction of cystatins results in suppression of TGF? signaling and inhibition of triple-negative breast cancer metastasis. Proc Natl Acad Sci U S A 115:E9580-E9589
Lilyquist, Jenna; Ruddy, Kathryn J; Vachon, Celine M et al. (2018) Common Genetic Variation and Breast Cancer Risk-Past, Present, and Future. Cancer Epidemiol Biomarkers Prev 27:380-394
Yu, Jia; Qin, Bo; Moyer, Ann M et al. (2018) DNA methyltransferase expression in triple-negative breast cancer predicts sensitivity to decitabine. J Clin Invest 128:2376-2388
Kannan, Nagarajan; Eaves, Connie J (2018) Macrophages stimulate mammary stem cells. Science 360:1401-1402
Guidugli, Lucia; Shimelis, Hermela; Masica, David L et al. (2018) Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches. Am J Hum Genet 102:233-248
Kurmi, Kiran; Hitosugi, Sadae; Wiese, Elizabeth K et al. (2018) Carnitine Palmitoyltransferase 1A Has a Lysine Succinyltransferase Activity. Cell Rep 22:1365-1373
Goetz, Matthew P; Sangkuhl, Katrin; Guchelaar, Henk-Jan et al. (2018) Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. Clin Pharmacol Ther 103:770-777
Baheti, Saurabh; Tang, Xiaojia; O'Brien, Daniel R et al. (2018) HGT-ID: an efficient and sensitive workflow to detect human-viral insertion sites using next-generation sequencing data. BMC Bioinformatics 19:271

Showing the most recent 10 out of 473 publications