Racial Disparity in Ductal Carcinoma in Situ: Risk-Predictive and Actionable Biomarkers for Early Intervention

Area of Science:

• Oncology
• Genetics
• Immunology

Background:

• Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer, but lacks biomarkers to differentiate indolent from aggressive lesions.
• Black women with DCIS experience higher progression rates, mortality, and are diagnosed with more aggressive subtypes than White women, despite similar healthcare access.
• This disparity suggests underlying biological and tissue microenvironmental factors influencing DCIS progression.

Purpose of the Study:

• To review emerging evidence on molecular and systemic changes driving racial disparities in DCIS progression.
• To highlight racial distinctions in key biological pathways and identify potential biomarkers associated with aggressive disease in Black women.
• To propose an integrated framework for understanding DCIS progression and reducing racial disparities in breast cancer outcomes.

Main Methods:

• Literature review synthesizing evidence on molecular pathways, epigenetic alterations, and immune microenvironment in DCIS.
• Analysis of racial differences in Wnt/β-catenin signaling, metabolic dysregulation, immune response, and genomic instability tolerance.
• Identification and discussion of candidate biomarkers (e.g., KIFC1, ACKR1/DARC) linked to aggressive DCIS in Black women.

Main Results:

• Racial disparities in DCIS progression are linked to distinct molecular pathways including Wnt/β-catenin signaling, metabolic dysregulation, immune remodeling, and genomic instability.
• Epigenetic alterations, obesity-associated inflammation, and immune dysregulation may contribute to these disparities during the pre-invasive stage.
• Candidate biomarkers like KIFC1 and ACKR1/DARC are disproportionately associated with aggressive DCIS in Black women, potentially driving progression.

Conclusions:

• DCIS progression is driven by coordinated molecular programs enabling survival under stress, not isolated alterations.
• Current risk assays incompletely capture these pathways and may underestimate biologically meaningful racial disparities.
• Pathway-level, microenvironment-informed, and population-representative approaches are needed for accurate DCIS risk stratification and to reduce breast cancer disparities.