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

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.