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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.

Collagen fiber orientation disorder from H&E images is prognostic for early stage breast cancer: clinical trial validation