Administrative Supplement to Cancer Center Support Grant (CCSG)

Project Summary
Early-onset breast cancer (EOBC), diagnosed in adults aged 18-49, exhibits alarming incidence increases of
1.4% annually in the U.S. compared to 0.7% in older cohorts. Among Asian American/Pacific Islander women,
incidence has risen by 2.7% annually, with particularly aggressive biology characterized by higher rates of triple-
negative and HER2-positive subtypes, and 10-15% lower 5-year survival rates. Despite rising incidence (1.4%
annually) and 10-15% lower survival rates, a critical knowledge gap remains: why healthy young adults develop
aggressive cancers decades earlier than expected. We hypothesize early-onset breast cancer arises from a
distinct molecular-physical structure axis where specific lifestyle factors drive unique physical tissue changes in
young women's normal breast tissue, creating cancer-prone microenvironments that bypass typical age-related
cancer development pathways. Our lab's developed computational pathology methods (ecPath, TLPath) enable
quantitative measurement of tissue architecture from standard H&E images. We will analyze 263 EOBC tumor
biopsies and 113 normal adjacent tumor (NAT) samples (44 from EOBC cases) from The Cancer Genome Atlas
(TCGA), identifying adjacent normal tissue architecture unique to EOBC transformation, connecting findings to
corresponding features in Genotype-Tissue Expression Project (GTEx, 514 normal breast samples) to identify
lifestyle and clinical factors accelerating cancer-prone tissue patterns, and mapping underlying molecular drivers.
This research will establish the first comprehensive molecular-lifestyle-physical feature axis unique to EOBC,
revealing how lifestyle factors accelerate cancer-prone tissue changes in young women and providing novel
preventive intervention targets.

Grant Number: 3P30CA030199-44S1
NIH Institute/Center: NIH
Principal Investigator: Paul Boutros