Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand how the tumor microenvironment (TME) changes with transition to IBC, we used Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to analyze 140 clinically annotated surgical resections covering the full spectrum of breast cancer progression. We compared normal, DCIS, and IBC tissues using machine learning tools for multiplexed cell segmentation, pixel-based clustering, and object morphometrics. Transition from DCIS to IBC was found to occur along a trajectory marked by coordinated shifts in location and function of myoepithelium, fibroblasts, and infiltrating immune cells in the surrounding stroma. Taken together, this comprehensive study within the HTAN Breast PreCancer Atlas offers insight into the etiologies of DCIS, its transition to IBC, and emphasizes the importance of the TME stroma in promoting these processes.

中文翻译：

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向浸润性乳腺癌的转移与肿瘤基质的结构和组成的进行性改变有关

导管原位癌（DCIS）是一种浸润前病变，被认为是浸润性乳腺癌（IBC）的前兆。为了了解肿瘤微环境（TME）随着向IBC过渡的变化，我们使用飞行时间多路离子束成像（MIBI-TOF）和37重抗体染色板分析了140例临床注释的手术切除，涵盖了所有乳腺癌进展。我们使用机器学习工具比较了正常，DCIS和IBC组织，以进行多路细胞分割，基于像素的聚类和对象形态计量学。发现从DCIS过渡到IBC的轨迹沿肌上皮，成纤维细胞和周围基质中浸润的免疫细胞的位置和功能协调移动的轨迹。在一起