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

Haojia Li; Kaustav Bera; Paula Toro; PingFu Fu; Zelin Zhang; Cheng Lu; Michael Feldman; Shridar Ganesan; Lori J Goldstein; Nancy E Davidson; Akisha Glasgow; Aparna Harbhajanka; Hannah Gilmore; Anant Madabhushi

doi:10.1038/s41523-021-00310-z

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

NPJ Breast Cancer. 2021 Aug 6;7(1):104. doi: 10.1038/s41523-021-00310-z.

Authors

Haojia Li¹, Kaustav Bera², Paula Toro², PingFu Fu³, Zelin Zhang⁴, Cheng Lu², Michael Feldman⁵, Shridar Ganesan⁶, Lori J Goldstein⁷, Nancy E Davidson⁸, Akisha Glasgow⁹, Aparna Harbhajanka⁹, Hannah Gilmore⁹, Anant Madabhushi^{10

11}

Affiliations

¹ Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH, USA. hxl735@case.edu.
² Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH, USA.
³ Case Western Reserve University, Department of Population and Quantitative Health Sciences, School of Medicine, Cleveland, OH, USA.
⁴ Nanjing University of Information Science and Technology, Jiangsu Key Laboratory of Big Data Analysis Technique, Nanjing, China.
⁵ University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
⁶ Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
⁷ Fox Chase Cancer Center, Philadelphia, PA, USA.
⁸ Fred Hutchinson Cancer Research Center, University of Washington, and Seattle Cancer Care Alliance, Seattle, WA, USA.
⁹ University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
¹⁰ Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH, USA. axm788@case.edu.
¹¹ Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH, USA. axm788@case.edu.

Abstract

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.

Abstract

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