  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 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 (...)
