Collagen fiber organization has been found to be implicated in breast cancer prognosis. In this study, we evaluated whether computerized features of Collagen Fiber Orientation Disorder in Tumor-associated Stroma (CFOD-TS) on Hematoxylin & Eosin (H&E) slide images were prognostic of Disease Free Survival (DFS) in early stage Estrogen Receptor Positive (ER+) Invasive Breast Cancers (IBC). A Cox regression model named M_CFOD-TS, was constructed using cohort S_t (N = 78) to predict DFS based on CFOD-TS features. The prognostic performance of M_CFOD-TS was validated on cohort S_v (N = 219), a prospective clinical trial dataset (ECOG 2197). M_CFOD-TS was prognostic of DFS in both S_t and S_v, independent of clinicopathological variables. Additionally, the molecular pathways regarding cell cycle regulation were identified as being significantly associated with M_CFOD-TS derived risk scores. Our results also found that collagen fiber organization was more ordered in patients with short DFS. Our study provided a H&E image-based pipeline to derive a potential prognostic biomarker for early stage ER+ IBC without the need of special collagen staining or advanced microscopy techniques.

已发现胶原纤维组织与乳腺癌预后有关。在这项研究中，我们评估了苏木精和曙红 (H&E) 幻灯片图像上肿瘤相关基质中胶原纤维定向障碍 (CFOD-TS) 的计算机化特征是否可预测早期雌激素受体阳性 (ER+) 的无病生存 (DFS) ) 浸润性乳腺癌 (IBC)。一个名为 M _{CFOD-TS 的}Cox 回归模型是使用队列 S _t ( N  = 78)构建的，以基于 CFOD-TS 特征预测 DFS。M _CFOD-TS的预后性能在队列 S _v ( N  = 219)、前瞻性临床试验数据集 (ECOG 2197) 上得到验证。M _CFOD-TS是 S _t和 S _v中 DFS 的预后，独立于临床病理变量。此外，关于细胞周期调节的分子途径被确定为与 M _CFOD-TS衍生的风险评分显着相关。我们的结果还发现，短 DFS 患者的胶原纤维组织更有序。我们的研究提供了一个基于 H&E 图像的管道，无需特殊的胶原染色或先进的显微镜技术，即可为早期 ER+IBC 推导出潜在的预后生物标志物。