Deep learning-enabled breast cancer hormonal receptor status determination from base-level H&E stains.

Journal: Nature communications
Published Date:

Abstract

For newly diagnosed breast cancer, estrogen receptor status (ERS) is a key molecular marker used for prognosis and treatment decisions. During clinical management, ERS is determined by pathologists from immunohistochemistry (IHC) staining of biopsied tissue for the targeted receptor, which highlights the presence of cellular surface antigens. This is an expensive, time-consuming process which introduces discordance in results due to variability in IHC preparation and pathologist subjectivity. In contrast, hematoxylin and eosin (H&E) staining-which highlights cellular morphology-is quick, less expensive, and less variable in preparation. Here we show that machine learning can determine molecular marker status, as assessed by hormone receptors, directly from cellular morphology. We develop a multiple instance learning-based deep neural network that determines ERS from H&E-stained whole slide images (WSI). Our algorithm-trained strictly with WSI-level annotations-is accurate on a varied, multi-country dataset of 3,474 patients, achieving an area under the curve (AUC) of 0.92 for sensitivity and specificity. Our approach has the potential to augment clinicians' capabilities in cancer prognosis and theragnosis by harnessing biological signals imperceptible to the human eye.

Authors

  • Nikhil Naik
    Salesforce Research, 575 High St, Palo Alto, CA, 94301, USA. nnaik@salesforce.com.
  • Ali Madani
    Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, 208A Stanley Hall #1762, Berkeley, CA, 94720-1762, USA.
  • Andre Esteva
    Artera, Inc., Los Altos, CA.
  • Nitish Shirish Keskar
    Salesforce Research, 575 High St, Palo Alto, CA, 94301, USA.
  • Michael F Press
    Department of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Ave, Los Angeles, CA, 90033, USA.
  • Daniel Ruderman
    Genentech Inc., South San Francisco, California, USA.
  • David B Agus
    Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, 12414 Exposition Blvd, Los Angeles, CA, 90064, USA.
  • Richard Socher
    Salesforce Research, 575 High St, Palo Alto, CA, 94301, USA.