This renewal application of the Mayo Clinic Breast Cancer SPORE is being submitted with full support of Mayo Clinic Cancer Center (MCCC) and Mayo Foundation to continue translational research directed at reducing the burden and mortality from breast cancer. The science of the SPORE includes four translational research projects: Project 1: "Risk assessment for carriers of Variants of Uncertain Significance (VUS) in the BRCA1 and BRCA2 breast cancer predisposition genes" will continue this clinically important and highly translational research that addresses a clear unmet need of many woman to determine their personal risk of breast cancer when tested for BRCA 1/2 and given the result of a VUS. Project 2: "Endoxifen as a novel hormonal therapy for breast cancer" is based on Mayo investigator derived preclinical data indicating that endoxifen has superior anti-tumor activity than tamoxifen. These data led NCI to develop clinical grade endoxifen, which will be used in a first-in-human phase I clinical trial in this SPORE project. Project 3: "Regulation of hormone resistant breast cancer by IGF and insulin system signaling" focuses on a novel approach to dealing with resistance to hormonal therapy by focusing on the role of the insulin receptor A isoform as a (co-)mediator of insulin growth factor pathway signaling. Additional pre-clinical studies are planned and complete IGF and estrogen receptor blockade will be examined in a phase II clinical trial that is notable for intensive biospecimen acquisition, including biopsies, for translational studies in the Co-Leaders'labs. Project 4: "Improving breast cancer risk prediction for women with benign breast disease" addresses the highly important need for better prediction of risk in the individual patient utilizing features present in the patient's benign breast tissue (BBD). This project will identify novel biomarkers and build a risk prediction model using the large Mayo BBD Cohort with subsequent validation in a SPORE-SPORE collaboration. These research projects are supported by three highly interactive cores: Core A: Administrative Core, Core B;. Biospecimen and Pathology Core, and Core C: Biostatistics 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 Development 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, core facilities, and the research programs in the SPORE are all integrated into the MCCC and, collectively, will advance knowledge and translate findings into the clinic for the benefit of women with, or at risk for, breast cancer.

Public Health Relevance

Breast cancer is the most common cancer in women and the Mayo Clinic Breast Cancer SPORE proposes to continue to conduct research that through translation will reduce morbidity and mortality from the disease. This will be accomplished through two projects addressing risk of developing breast cancer and two projects directed at improving therapy of breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA116201-09
Application #
8724923
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (M1))
Program Officer
Kuzmin, Igor A
Project Start
2005-09-21
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
9
Fiscal Year
2014
Total Cost
$2,783,997
Indirect Cost
$707,115
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Abubakar, Mustapha; Orr, Nick; Daley, Frances et al. (2016) Prognostic value of automated KI67 scoring in breast cancer: a centralised evaluation of 8088 patients from 10 study groups. Breast Cancer Res 18:104
Cichon, Magdalena A; Moruzzi, Megan E; Shqau, Tiziana A et al. (2016) MYC Is a Crucial Mediator of TGFβ-Induced Invasion in Basal Breast Cancer. Cancer Res 76:3520-30
de la Hoya, Miguel; Soukarieh, Omar; López-Perolio, Irene et al. (2016) Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms. Hum Mol Genet 25:2256-2268
Durand, Nisha; Bastea, Ligia I; Long, Jason et al. (2016) Protein Kinase D1 regulates focal adhesion dynamics and cell adhesion through Phosphatidylinositol-4-phosphate 5-kinase type-l γ. Sci Rep 6:35963
Shi, Jiajun; Zhang, Yanfeng; Zheng, Wei et al. (2016) Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer. Int J Cancer 139:1303-17
Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B et al. (2016) Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium. Hum Genet 135:137-54
(2016) Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus. Nat Commun 7:12675
Li, Xu; Wang, Wenqi; Xi, Yuanxin et al. (2016) FOXR2 Interacts with MYC to Promote Its Transcriptional Activities and Tumorigenesis. Cell Rep 16:487-97
Schmidt, Marjanka K; Hogervorst, Frans; van Hien, Richard et al. (2016) Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers. J Clin Oncol 34:2750-60
Chiba, Akiko; Hoskin, Tanya L; Hallberg, Emily J et al. (2016) Impact that Timing of Genetic Mutation Diagnosis has on Surgical Decision Making and Outcome for BRCA1/BRCA2 Mutation Carriers with Breast Cancer. Ann Surg Oncol 23:3232-8

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