This application proposes the fourth renewal of the UNC Breast Cancer SPORE. Originally funded in 1992, the UNC SPORE has used significant institutional investment and the distinctive SPORE elements: funding flexibility, interdisciplinary collaboration, bidirectional translational research, developmental programs, and interSPORE partners to build an outstanding program in translational breast cancer research. The UNC SPORE'S combination of population-based research, molecular genetics, breast cancer biology, health disparities research, tissue-acquiring clinical trials, database development, and expertise in bioinformatics and biostatistics was made possible with long-term SPORE support. Interaction between disciplines has resulted in substantial productivity, as measured by important findings published in high impact journals, career advancement for junior investigators, developmental research leading to grants and new SPORE projects, multiple funded interSPORE collaborations, and innovative approaches to breast cancer etiology, classification, prognosis, and therapy. Our projects are conceptually linked by studies of breast cancer molecular intrinsic subtypes, particularly the triple negative breast cancers, basal-like cancer and a newly-defined subtype, Claudin low. We feature a nation leading population science study of breast cancer and minority disparities, the Carolina Breast Cancer Study (CBCS), entering its 20th year of SPORE funding. Our molecular genetics translational group is developing new technology for intrinsic subtyping with which to analyze clinically-annotated samples from CBCS and local, national, and international trials. Novel translational studies of gene expression, tumor microevironment and a systems approach to the kinome will utilize both preclinical models and human tumors. The projects are entitled: 1) Carolina Breast Cancer Study: Genomic and epidemiologic determinants of breast cancer minority disparities. 2) Targeting the infiltrating immune cells in Claudin-low tumors. 3) Development and validation of predictive markers for triple negative breast cancers. 4) Stromal response subtypes in breast cancer risk and progression 5) Quantitative proteomic analysis of the human kinome in Claudin-low and basal-like breast cancer Five of the co-Project leaders are products of the SPORE career development program. Two of the projects resulted from our SPORE Developmental Research Program. The SPORE is supported by exceptional infrastructure and institutional commitment from the UNC Lineberger Comprehensive Cancer Center and three SPORE-funded cores: Pathology, Genomics, Biostatistics &Bioinformatics, and Administration.

Public Health Relevance

The UNC Breast Cancer SPORE contributes to the clinical application of molecular subtyping to breast cancer discovery, prognostication, conduct of clinical trials, and understanding of minority disparities in breast cancer. Our projects continue to explore the effect of intrinsic subtype on the predisposition, progression, and therapeutic resistance of difficult-to-treat breast cancers. UNO SPORE's technology development, population-based studies, and analysis of clinical trials will have substantial translational impact.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA058223-21S1
Application #
8907367
Study Section
Special Emphasis Panel (ZCA1-RPRB-0 (M1))
Program Officer
Ogunbiyi, Peter
Project Start
1997-08-05
Project End
2017-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
21
Fiscal Year
2014
Total Cost
$97,292
Indirect Cost
$33,284
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Mobley, Robert J; Raghu, Deepthi; Duke, Lauren D et al. (2017) MAP3K4 Controls the Chromatin Modifier HDAC6 during Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition. Cell Rep 18:2387-2400
Kohler, Racquel E; Gopal, Satish; Miller, Anna R et al. (2017) A framework for improving early detection of breast cancer in sub-Saharan Africa: A qualitative study of help-seeking behaviors among Malawian women. Patient Educ Couns 100:167-173
Valle, Carmina G; Deal, Allison M; Tate, Deborah F (2017) Preventing weight gain in African American breast cancer survivors using smart scales and activity trackers: a randomized controlled pilot study. J Cancer Surviv 11:133-148
Sharma, Priyanka; López-Tarruella, Sara; García-Saenz, Jose Angel et al. (2017) Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts. Clin Cancer Res 23:649-657
Mullooly, Maeve; Yang, Hannah P; Falk, Roni T et al. (2017) Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients. Breast Cancer Res 19:8
Hoffman, Joshua D; Graff, Rebecca E; Emami, Nima C et al. (2017) Cis-eQTL-based trans-ethnic meta-analysis reveals novel genes associated with breast cancer risk. PLoS Genet 13:e1006690
Visvanathan, Kala; Fackler, MaryJo S; Zhang, Zhe et al. (2017) Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study. J Clin Oncol 35:751-758
Zawistowski, Jon S; Bevill, Samantha M; Goulet, Daniel R et al. (2017) Enhancer Remodeling during Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacologic Targeting of the P-TEFb Complex. Cancer Discov 7:302-321
Bowerman, Charles J; Byrne, James D; Chu, Kevin S et al. (2017) Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer. Nano Lett 17:242-248
Heng, Yujing J; Lester, Susan C; Tse, Gary Mk et al. (2017) The molecular basis of breast cancer pathological phenotypes. J Pathol 241:375-391

Showing the most recent 10 out of 548 publications