Project 3: Inter-Relationships and Prognostic Significance of Breast Cancer Radiomic Risk Features, Tissue Microenvironment, and Adiposity

SUMMARY / ABSTRACT The risk of breast cancer among U.S. women dramatically differs across racial and ethnic populations. Nonetheless, Asian American and Native Hawaiian/Pacific Islander (AANHPI) ethnic minority women have been historically underrepresented in breast cancer research. Consequently, there are major gaps in understanding

the basis of disparities in these populations including high incidence and mortality among Native Hawaiians and a steadily rising incidence with comparatively favorable outcomes among Japanese Americans. Obesity and breast density, established breast cancer risk factors, vary widely across AANHPI women and have direct

implications for mammographic screening and primary prevention. Our research to date provides strong evidence that body fat distribution, including visceral adipose tissue (VAT), is an important predictor of breast cancer risk. The influence of adiposity on breast density and other aspects of breast architecture that can be

discerned through mammographic screening (e.g. radiomic features) is not well understood. Our long-term goal is to elucidate the breast cancer disparities seen in understudied minority AANHPI subgroups (Native Hawaiian, Micronesian, Japanese, Chinese, Filipina) that can be translated to improved prevention, early detection, and

therapeutic strategies. Our central hypothesis is that established radiomic risk features have unique associations with breast cancer incidence in AANHPI subgroups and that they are correlated with tissue biomarkers of risk and prognosis and with obesity, especially VAT. Study resources include the statewide

Hawai`i Pacific Islands Mammography Registry linked to the SEER Hawai`i Tumor Registry and its Residual Tissue Repository (RTR), and to the Hawai`i component of the Multiethnic Cohort Study (MEC). Our study is focused on the minority health of AANHPI, with the following aims: 1) Characterize the relationships of

established breast imaging radiomic risk features with tissue protein biomarker expression profiles reflecting the tissue microenvironment and breast cancer prognosis and with disease-specific survival; 2) Characterize the joint relationships of breast radiomic risk features and different measures of adiposity, including VAT, with

post-menopausal breast cancer risk among Native Hawaiian, Japanese American, and White MEC participants. 3) Calibrate commonly used risk prediction models for breast cancer by including established breast radiomic (AI and machine learning) risk features from 2D and 3D mammography in AAPHI and White women overall and by estrogen/progesterone receptor and HER-2 status. The expected outcome of the

proposed study is to further our understanding of unique relationships between imaging biomarkers derived from advanced machine learning approaches and race/ethnicity, tissue molecular characteristics and adiposity phenotypes, which will improve risk and prognosis model accuracy and better identify high risk women for further

assessment or tailored therapy.