SPORE in Breast Cancer

Overall – Abstract
This is the competitive renewal for year 30-34 of the UNC Breast Cancer SPORE. SPORE goals and aims
have been reinvigorated every five years with advice from a robust advocate group and an insightful series of
external and internal advisors. However, the emphasis on racial, ethnic, and lower socioeconomic status (SES)
breast cancer disparities, genomic technology and analytic capacity, subtyping/biomarker research and
therapeutic resistance have been consistent, as has the recruitment and mentoring of junior faculty. Career
development has returned dividends, with multiple SPORE leaders being previous recipients of CEP funds.
One constant since 1992 is a biospecimen, epidemiologic, and clinical data-rich population-based Carolina
Breast Cancer Study (CBCS). CBCS Phase 3 (3,000 new cases, 2008-2013) has collected ten years of
follow-up; CBCS 4 will recruit an additional 3,000 new cases, again oversampling Black (50% of study
population) and younger (50% of study) women, who are typically understudied in genomic and health services
research. CBCS has made seminal contributions to our understanding of Triple Negative Breast Cancer
(TNBC) and other subtypes in Black and White populations with 230+ papers published (47 from this cycle),
many high impact and heavily cited. Understanding and addressing racial disparities in breast cancer is a
longstanding emphasis of this SPORE, and CBCS in particular, which will focus on a cells-to-society model
wherein tumor biology and immune response are part of a complex system that includes differences in health
care access and social environments. All 4 projects, which share a focus on TNBC that disproportionately
afflicts Black and young women, will contribute to understanding across this spectrum.
Continued institutional investment, averaging $2-$2.5M yearly, allows the renewed SPORE to: i) Incorporate
new technologies and methods; ii) Develop infrastructure for population and translational research; and iii)
Support junior and mid-level faculty from the population, basic, and clinical sciences. In the past 5 years the
CEP supported 17 new faculty (12 women and 8 URM individuals) who successfully competed for foundation,
cooperative group, and NCI funding. DRP funded multiple collaborative projects (two are among the 4 Projects
in this application). With EAB, Advocate, and Executive Committee input, the MPIs Perou and Carey selected
four Projects, focusing on disparities, biomarkers, immune-based therapeutics and TNBC therapeutic
resistance: Project #1 – Carolina Breast Cancer Study (CBCS): Linking Tumor Biology to Social Determinants
(Troester PhD, and Reeder-Hayes MD, MBA MSc), Project #2 – Determinants of Response and Resistance to
DNA-Damaging Radiation Plus Immunotherapy Combinations in TNBC (Gupta MD, PhD, and Vincent MD),
Project #3 – Development of Novel Therapies and Biomarkers for TNBC (Perou PhD, and Carey MD, ScM),
Project #4 – Activity of CAR-T Cell Therapy for Patients with Metastatic TNBC (Dotti PhD, Serody MD, and
Dees MD, ScM).