ArticleBreast cancer research : BCR2025
Evolutionary measures show that recurrence of DCIS is distinct from progression to breast cancer.
Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Integrated Multi-Omics Reveals Cellular States and Microenvironmental Remodeling in Coexisting DCIS and IDC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Diagnosis of Extensive DCIS with Progressive Microcalcifications over a Period of 11 Years.Diagnostics (Basel, Switzerland) · 2026Article
- Metabolic plasticity of sphingolipids governs cancer cell fitness in acidic tumor ecosystems.bioRxiv : the preprint server for biology · 2026Article
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Abstract
backgroundProgression from pre-cancers like ductal carcinoma in situ (DCIS) to invasive disease (cancer) is driven by somatic evolution and is altered by clinical interventions. We hypothesized that genetic and/or phenotypic intra-tumor heterogeneity would predict clinical outcomes for DCIS since it serves as the substrate for natural selection among cells.
methodsWe profiled two samples from two geographically distinct foci from each DCIS in both cross-sectional (n = 119) and longitudinal cohorts (n = 224), with whole exome sequencing, low-pass whole genome sequencing, and a panel of immunohistochemical markers.
resultsIn the longitudinal cohorts, the only statistically significant associations with time to non-invasive DCIS recurrence were the combination of treatment (lumpectomy only vs mastectomy or lumpectomy with radiation, HR 12.13, p = 0.003, Wald test with FDR correction), ER status (HR 0.16 for ER+ compared to ER-, p = 0.0045), and divergence in SNVs between the two samples (HR 1.33 per 10% divergence, p = 0.018). SNV divergence also distinguished between pure DCIS and DCIS synchronous with invasive disease in the cross-sectional cohort. In contrast, the only statistically significant associations with time to progression to invasive disease were the combination of the width of the surgical margin (HR 0.67 per mm, p = 0.043) and the number of mutations that were detectable at high allele frequencies (HR 1.30 per 10 SNVs, p = 0.02). No predictors were significantly associated with both DCIS recurrence and progression to invasive disease, suggesting that the evolutionary scenarios that lead to these clinical outcomes are markedly different.
conclusionsThese results imply that recurrence with DCIS is a clinical and biological process different from invasive progression.
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