A population-level digital histologic biomarker for enhanced prognosis of invasive breast cancer

• Published in: Nature medicine Vol. 30; no. 1; pp. 85 - 97
• Main Authors: Amgad, Mohamed, Hodge, James M., Elsebaie, Maha A. T., Bodelon, Clara, Puvanesarajah, Samantha, Gutman, David A., Siziopikou, Kalliopi P., Goldstein, Jeffery A., Gaudet, Mia M., Teras, Lauren R., Cooper, Lee A. D.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 2024; Nature Publishing Group
• Subjects: 631/114/1305; 631/114/1564; 631/67/1347; 639/166/985; 692/53/2422; Biomarkers; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cellular structure; Deep learning; Disease prevention; Genomes; Infectious Diseases; Lung cancer; Medical prognosis; Metabolic Diseases; Metastases; Molecular Medicine; Neurosciences; Ovarian cancer; Prognosis; Survival; Tumor microenvironment; Tumors
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/s41591-023-02643-7

Breast cancer is a heterogeneous disease with variable survival outcomes. Pathologists grade the microscopic appearance of breast tissue using the Nottingham criteria, which are qualitative and do not account for noncancerous elements within the tumor microenvironment. Here we present the Histomic Prognostic Signature (HiPS), a comprehensive, interpretable scoring of the survival risk incurred by breast tumor microenvironment morphology. HiPS uses deep learning to accurately map cellular and tissue structures to measure epithelial, stromal, immune, and spatial interaction features. It was developed using a population-level cohort from the Cancer Prevention Study-II and validated using data from three independent cohorts, including the Prostate, Lung, Colorectal, and Ovarian Cancer trial, Cancer Prevention Study-3, and The Cancer Genome Atlas. HiPS consistently outperformed pathologists in predicting survival outcomes, independent of tumor–node–metastasis stage and pertinent variables. This was largely driven by stromal and immune features. In conclusion, HiPS is a robustly validated biomarker to support pathologists and improve patient prognosis. Deep learning enables comprehensive and interpretable scoring for breast cancer prognosis prediction, outperforming pathologists in multicenter validation and providing insight on prognostic biomarkers.