{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:55Z","timestamp":1785437035250,"version":"3.56.0"},"reference-count":201,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Center","award":["P067152"],"award-info":[{"award-number":["P067152"]}]},{"award":["P067152"],"award-info":[{"award-number":["P067152"]}],"id":[{"id":"https:\/\/ror.org\/0065zqt33","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ductal carcinoma in situ (DCIS) is a non-invasive precursor to invasive breast cancer. DCIS incidence continues to rise, yet its clinical management remains constrained by the absence of reliable biomarkers that can adequately distinguish indolent lesions from those with high invasive potential, to circumvent over- or under-treatment. Black women with DCIS are significantly more likely to progress to invasive breast cancer, are disproportionately diagnosed with high-grade, hormone receptor-negative lesions, and experience elevated risk of recurrence and mortality relative to White women with DCIS. These disparities persist despite comparable access to screening and treatment, suggesting underlying biological and tissue microenvironmental factors. This review synthesizes emerging evidence implicating early molecular and systemic changes that may be driving the disparity in DCIS progression. We highlight racial distinctions in interconnected pathways involving Wnt\/\u03b2-catenin signaling, metabolic and nutritional dysregulation, immune microenvironment remodeling, and cellular tolerance of genomic instability. We further discuss how epigenetic alterations, obesity-associated inflammation, and immune dysregulation may arise during the pre-invasive stage that intersect with social and environmental exposures to influence racial differences in lesion fate. We spotlight candidate biomarkers disproportionately associated with aggressive disease in Black women\u2014including KIFC1, a mediator of centrosome clustering and genomic instability tolerance, and ACKR1\/DARC, a regulator of chemokine gradients and immune trafficking\u2014as potential drivers of progression-permissive states. This review advances an integrated, equity-informed framework for DCIS progression that links early tumor evolution to coordinated alterations in genomic instability, immune regulation, metabolic signaling, and stress-adaptive pathways. Importantly, we propose that DCIS progression is governed not by isolated molecular alterations but by coordinated programs that enable survival under genomic and immunologic stress. Current clinical risk assays, which primarily capture tumor-intrinsic proliferation and hormone signaling, do not fully resolve these pathways and may therefore incompletely reflect biologically meaningful racial disparities. This synthesis underscores the need for pathway-level, microenvironment-informed, and population-representative approaches to DCIS risk stratification. Advancing such frameworks will be essential for identifying actionable biomarkers, refining early intervention strategies, and ultimately reducing racial disparities in breast cancer outcomes.<\/jats:p>","DOI":"10.3390\/cancers18111794","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:19:42Z","timestamp":1780316382000},"page":"1794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Racial Disparity in Ductal Carcinoma in Situ: Risk-Predictive and Actionable Biomarkers for Early Intervention"],"prefix":"10.3390","volume":"18","author":[{"given":"Dana","family":"Franklin","sequence":"first","affiliation":[{"name":"City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmashree","family":"Rida","sequence":"additional","affiliation":[{"name":"Rowland Hall, Salt Lake City, UT 84102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-2881","authenticated-orcid":false,"given":"Nikita","family":"Jinna","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41416-019-0478-6","article-title":"Ductal carcinoma in situ: To treat or not to treat, that is the question","volume":"121","author":"Lips","year":"2019","journal-title":"Br. 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