Grant Number:	1R01CA301785-01A1 Interpret this number
Primary Investigator:	Loo, Lenora
Organization:	University Of Hawaii At Manoa
Project Title:	Identification of Biological Mechanisms and Risk Factors Contributing to Progression of Dcis to Invasive Breast Cancer Among Aanhpi Populations.
Fiscal Year:	2026

ABSTRACT Ductal carcinoma in situ (DCIS), the earliest stage (Stage 0) of breast cancer, accounts for approximately 20% of newly diagnosed breast cancers in the U.S. DCIS results from the over-proliferation of breast epithelial cells that remain confined within the breast ductal system. It is a non-obligate precursor to invasive breast cancer, with fewer than 50% of DCIS patients subsequently progressing to invasive cancer. Therefore, DCIS presents a clinical challenge: discriminating patients at high risk of progression to invasive breast cancer from those patients with an indolent DCIS tumor that will not. The ability to accurately stratify DCIS tumors by risk of progression is essential for guiding a more precise treatment course, thereby minimizing the potential for under- or over- treatment for this patient population. Moreover, there are differences in risk of DCIS progression among different racial and ethnic groups, including understudied U.S. minorities. We have previously reported stark disparities in DCIS risk of progression across Asian American and Native Hawaiian/Pacific Islander (AANHPI) patients. Specifically, Native Hawaiian, Filipino, and Japanese DCIS patients had an increased risk of being diagnosed with a subsequent ipsilateral invasive breast cancer compared to Whites. Our preliminary studies have identified lifestyle and sociodemographic risk factors for DCIS in our multiethnic population as well as variation in breast tumor markers in AANHPI patients compared to Whites. Collectively, our findings underscore the critical gap in knowledge of multilevel factors that contribute to racial and ethnic differences in the pathogenesis of early breast cancer. We will leverage the comprehensive exposure data and biospecimens of the Multiethnic Cohort and the Hawaii Tumor Registry to address our central hypothesis that differences in social and biological factors contribute to racial and ethnic disparities in risk of DCIS progression to invasive breast cancer. We propose to identify lifestyle, sociodemographic, and clinical predictors of risk of DCIS progression to invasive breast cancer in AANHPI (Aim 1); identify DCIS tumor molecular mechanisms predicting risk of progression and non- progression, including features specific to AANHPI (Aim 2); identify DCIS tumor molecular mechanisms of progression by comparing paired DCIS and subsequent invasive tumors from the same individual (Aim 3). Our overall objective is to elucidate the etiology and the underlying biological mechanisms with the long-term goal of improving risk prediction of DCIS progression to invasive breast cancer among the largely understudied AANHPI populations.





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