Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts

Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical out-comes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Transla-tional Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classi-fier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell com-positions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.

Automated summary

Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC) with variable progression. By analyzing 774 DCIS samples, we identified 812 genes associated with ipsilateral recurrence within 5 years and developed a classifier to predict DCIS or IBC recurrence. Pathways related to recurrence include proliferation, immune response, and metabolism. Our approach generated a spatially resolved atlas of breast precancers using in situ methods, allowing direct comparison and correlation with conventional pathology findings, disease states, and clinical outcomes.