Performance of externally validated machine learning models based on histopathology images for the diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer: A systematic review

Abstract

Numerous machine learning (ML) models have been developed for breast cancer using various types of data. Successful external validation (EV) of ML models is important evidence of their generalizability. The aim of this systematic review was to assess the performance of externally validated ML models based on histopathology images for diagnosis, classification, prognosis, or treatment outcome prediction in female breast cancer. A systematic search of MEDLINE, EMBASE, CINAHL, IEEE, MICCAI, and SPIE conferences was performed for studies published between January 2010 and February 2022. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed, and the results were narratively described. Of the 2011 non-duplicated citations, 8 journal articles and 2 conference proceedings met inclusion criteria. Three studies externally validated ML models for diagnosis, 4 for classification, 2 for prognosis, and 1 for both classification and prognosis. Most studies used Convolutional Neural Networks and one used logistic regression algorithms. For diagnostic/classification models, the most common performance metrics reported in the EV were accuracy and area under the curve, which were greater than 87% and 90%, respectively, using pathologists' annotations/diagnoses as ground truth. The hazard ratios in the EV of prognostic ML models were between 1.7 (95% CI, 1.2-2.6) and 1.8 (95% CI, 1.3-2.7) to predict distant disease-free survival; 1.91 (95% CI, 1.11-3.29) for recurrence, and between 0.09 (95% CI, 0.01-0.70) and 0.65 (95% CI, 0.43-0.98) for overall survival, using clinical data as ground truth. Despite EV being an important step before the clinical application of a ML model, it hasn't been performed routinely. The large variability in the training/validation datasets, methods, performance metrics, and reported information limited the comparison of the models and the analysis of their results. Increasing the availability of validation datasets and implementing standardized methods and reporting protocols may facilitate future analyses.

Keywords: Breast neoplasms; Machine learning; Pathology; Systematic review; Validation studies.

Fig. 1

PRISMA flow diagram of the studies identification process for the systematic review.

Fig. 2

Distribution of the records reviewed during the Title/Abstract screening by year (January 1, 2010–February 28, 2022).

Fig. 3

Prediction model Risk Of Bias Assessment Tool (PROBAST) Graphical presentation—(1) risk of bias results and (2) applicability.

Fig. 4

ML models site-specific iterative development steps review.

Fig. 5

Record that passed the Title/Abstract screening and the full-text screening.

Fig. 6

Record that passed the Title/Abstract screening and the full-text screening.

Fig. 7

Record that passed the Title/Abstract screening but did not pass the full-text screening (because EV was not performed).

Fig. 8

Record that passed the Title/Abstract screening but did not pass the full-text screening (because EV was not performed).

Fig. 9

Record that did not pass the Title/Abstract screening (because EV was not performed).

Fig. 10

Record that did not pass the Title/Abstract screening (because the model was only trained with microarray and clinical data).

Fig. 11

Record that did not pass the Title/Abstract screening (because the model was only trained with ultrasound images).

Fig. 12

Record that did not pass the Title/Abstract screening (because the model was developed to detect mitoses).

Fig. 13

Record that did not pass the Title/Abstract screening (because the model was developed to predict the expression of biomarkers).