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Peer-reviewedCC BY 4.0Frontiers in Oncology

A reproducible open-data framework for interpretable breast cancer diagnosis and cytopathology education

  1. 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University
  2. 2Department of Nuclear Medicine, The First Affiliated Hospital of University of Science and Technology of China (USTC)
  3. 3Department of Oncology, The 901 Hospital of the Joint Logistics Support Force of the People’s Liberation Army of China

Abstract

Introduction: Quantitative nuclear morphology links cytopathological assessment with interpretable diagnostic modeling and provides a practical foundation for teaching medical artificial intelligence. This study evaluated a reproducible framework that connects nuclear feature interpretation, malignant-versus-benign classification, and evidence-based assessment of diagnostic decisions.

Methods: The Wisconsin Diagnostic Breast Cancer dataset included 569 fine-needle aspiration samples (212 malignant and 357 benign) represented by 30 image-derived nuclear features. Seven supervised classifiers were compared using nested stratified cross-validation with five outer folds and four inner folds. Assessment covered ROC-AUC, precision-recall performance, probability calibration, training-derived decision thresholds, exploratory decision-curve analysis, feature importance, and leakage-controlled feature reduction.

Results: The radial basis function support vector machine achieved a ROC-AUC of 0.995, while the interpretable linear support vector machine (SVM) achieved 0.994, without a significant pairwise difference from the radial basis function SVM or logistic regression. For the linear SVM, fold-specific Youden thresholds yielded held-out accuracy of 0.981, sensitivity of 0.962, specificity of 0.992, F1-score of 0.974, and Matthews correlation coefficient of 0.959. Sensitivity-prioritized thresholding increased sensitivity to 0.991, with specificity of 0.866. The Brier score was 0.021. Nuclear texture, size, symmetry, and contour-related characteristics contributed prominently to model interpretation. A leakage-controlled 20-feature model retained a ROC-AUC of 0.996 and a precision-recall area under the curve of 0.994.

Discussion: The framework integrates quantitative cytopathology with reproducible model appraisal in a coherent teaching sequence. Nuclear feature distributions and importance patterns connect cellular morphology with diagnostic reasoning; classifier comparisons, calibration, and confusion matrices illustrate distinct dimensions of model performance; and alternative operating thresholds show how predictive probabilities translate into diagnostic decisions. Nested validation and reduced-feature analysis furnish practical examples for teaching data partitioning, feature redundancy, interpretability, and critical evaluation of medical AI. This shared analytical pathway provides case-based material for cytopathology, oncology, and interdisciplinary medical data science education.

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BibTeX
@article{li2026reproducible,
  title = {{A reproducible open-data framework for interpretable breast cancer diagnosis and cytopathology education}},
  author = {Min Li and Xinxin Zhang and Xiaosu Xie and Yu Shi and Xueyang Hu and Nana Huang and Zilu Wang},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1921082},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1921082/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A reproducible open-data framework for interpretable breast cancer diagnosis and cytopathology education
AU  - Min Li
AU  - Xinxin Zhang
AU  - Xiaosu Xie
AU  - Yu Shi
AU  - Xueyang Hu
AU  - Nana Huang
AU  - Zilu Wang
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1921082
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1921082/full
AB  - Introduction: Quantitative nuclear morphology links cytopathological assessment with interpretable diagnostic modeling and provides a practical foundation for teaching medical artificial intelligence. This study evaluated a reproducible framework that connects nuclear feature interpretation, malignant-versus-benign classification, and evidence-based assessment of diagnostic decisions.  Methods: The Wisconsin Diagnostic Breast Cancer dataset included 569 fine-needle aspiration samples (212 malignant and 357 benign) represented by 30 image-derived nuclear features. Seven supervised classifiers were compared using nested stratified cross-validation with five outer folds and four inner folds. Assessment covered ROC-AUC, precision-recall performance, probability calibration, training-derived decision thresholds, exploratory decision-curve analysis, feature importance, and leakage-controlled feature reduction.  Results: The radial basis function support vector machine achieved a ROC-AUC of 0.995, while the interpretable linear support vector machine (SVM) achieved 0.994, without a significant pairwise difference from the radial basis function SVM or logistic regression. For the linear SVM, fold-specific Youden thresholds yielded held-out accuracy of 0.981, sensitivity of 0.962, specificity of 0.992, F1-score of 0.974, and Matthews correlation coefficient of 0.959. Sensitivity-prioritized thresholding increased sensitivity to 0.991, with specificity of 0.866. The Brier score was 0.021. Nuclear texture, size, symmetry, and contour-related characteristics contributed prominently to model interpretation. A leakage-controlled 20-feature model retained a ROC-AUC of 0.996 and a precision-recall area under the curve of 0.994.  Discussion: The framework integrates quantitative cytopathology with reproducible model appraisal in a coherent teaching sequence. Nuclear feature distributions and importance patterns connect cellular morphology with diagnostic reasoning; classifier comparisons, calibration, and confusion matrices illustrate distinct dimensions of model performance; and alternative operating thresholds show how predictive probabilities translate into diagnostic decisions. Nested validation and reduced-feature analysis furnish practical examples for teaching data partitioning, feature redundancy, interpretability, and critical evaluation of medical AI. This shared analytical pathway provides case-based material for cytopathology, oncology, and interdisciplinary medical data science education.
SN  - 2234-943X
ER  -