Differences in Molecular Subtype Reference Standards Impact AI-based Breast Cancer Classification with Dynamic...

Background Breast cancer tumors can be identified as different luminal molecular subtypes depending on either immunohistochemical (IHC) staining or St Gallen criteria that includes Ki-67. Purpose To characterize molecular subtypes and understand the impact of disagreement among IHC and St Gallen molecular subtype reference standards on artificial intelligence classification of luminal A and luminal B tumors with use of radiomic features extracted from dynamic contrast-enhanced (DCE) MRI scans. Materials and Methods In this retrospective study, 28 radiomic features previously extracted from DCE-MRI scans of breast tumors imaged between February 2015 and October 2017 were examined in the following groups: (a) tumors classified as luminal A by both reference standards ("agreement"), (b) tumors classified as luminal A by IHC and luminal B by St Gallen ("disagreement"), and (c) tumors classified as luminal B by both ("agreement"). Luminal A or luminal B tumor classification with use of radiomic features was conducted with use of three sets: (a) IHC molecular subtyping, (b) St Gallen molecular subtyping, and (c) agreement tumors. The Kruskal-Wallis test was followed by the Mann-Whitney U test to determine pair-wise differences of radiomic features among agreement and disagreement tumors. Fivefold cross-validation with use of stepwise feature selection and linear discriminant analysis classified tumors in each set, with performance measured with use of area under the receiver operating characteristic curve (AUC). Results A total of 877 breast cancer tumors from 872 women (mean age, 48 years [range, 19-75 years]) were analyzed. Six features (sphericity, irregularity, surface area to volume ratio, variance of radial gradient histogram, sum average, volume of most enhancing voxels) were different (P ≤ .001) among agreement and disagreement tumors. AUC (median, 0.74 [95% CI: 0.68, 0.80]) was higher than when using tumors subtyped by either reference standard (IHC, 0.66 [0.60, 0.71], P = .003; St Gallen, 0.62 [0.58, 0.67], P = .001). Conclusion Differences in reference standards can hinder artificial intelligence classification performance of luminal molecular subtypes with dynamic contrast-enhanced MRI. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bae in this issue.