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 outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium (TBCRC) 038 study and the Resource of Archival Breast Tissue (RAHBT) cohorts. We identify 812 genes associated with ipsilateral recurrence within five years from treatment and develop a classifier 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 compositions 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. Strand et al. have performed a large, comprehensive study to generate a spatially resolved breast precancer atlas. They present a prognostic classifier that predicts both precancer recurrence and invasive progression, which may form the basis for a future clinical test to guide breast precancer treatment.

导管癌原位（DCIS）是浸润性乳腺癌（IBC）最常见的前体，具有变化的倾向。我们通过分析来自转化乳腺癌研究联盟（TBCRC）038研究和档案乳腺组织（RAHBT）COHORTS的54年患者中位数的中位随访774例DCIS样品，对DCI进行了多尺度，整合的分子分析。我们在治疗后五年内确定了与同侧复发相关的812个基因，并开发了一个分类器，该分类器可以预测两个队列中DCIS或IBC复发。与复发有关的途径包括增殖，免疫反应和代谢。鉴定出不同的基质表达模式和免疫细胞组成。我们采用原位方法的多尺度方法来产生乳腺癌的空间分析地图集，在这种方法中，可以直接比较互补方式并与常规病理学发现，疾病状态和临床结果进行比较。 Strand等。已经进行了一项大型，全面的研究，以产生空间分辨的乳房预科师地图集。他们提出了预后的分类器，该分类器既可以预测预科生的复发和侵入性进展，又可能构成未来临床测试以指导乳腺癌治疗的基础。