A Robustness-Oriented Quantum–Classical Hybrid Machine Learning Pipeline for Breast Cancer Diagnosis: External Validation, Explainability, and Rigorous Benchmarking in the NISQ Era
Background: Breast cancer remains a leading cause of cancer-related mortality, and reliable computational decision support is increasingly viewed as a complement to expert pathological assessment rather than a replacement for it. Variational quantum classifiers (VQCs) and Quantum Support Vector Machines (QSVMs) have recently been promoted as candidate models for medical classification, yet most published comparisons rely on internal hold-out validation alone and report only a single point estimate of discrimination, omitting calibration, decision-analytic value, and explainability—three ingredients that any clinically credible model must furnish. Methods: We assembled a complete quantum–classical machine learning pipeline and evaluated it under a deliberately stringent protocol designed to expose, rather than conceal, the limitations of current Noisy Intermediate-Scale Quantum (NISQ)-era models. The analytical hypothesis was conservative and stated in advance; in light of saturated classical baselines on this benchmark, we did not anticipate a quantum advantage in raw discrimination, and we framed the study as a methodological probe rather than as a competition. Using the Wisconsin Diagnostic Breast Cancer (WDBC) dataset (n = 569) for development and an independent Wisconsin Original (WBC) cohort (n = 683) for external validation, we benchmarked five classical learners (XGBoost, LightGBM, CatBoost, RandomForest, RBF-SVM), two quantum models (an eight-qubit VQC implemented in PennyLane and a ZZ-feature-map QSVM implemented in Qiskit), and a stacked hybrid ensemble. The evaluation framework combined Optuna-driven hyperparameter optimisation, internal–external cross-validation, and external validation on the independent WBC cohort. Robustness and interpretability were then probed through circuit depth and embedding rotation ablation, depolarising noise stress tests, learning curve and feature stability analysis, decision curve analysis, and dual SHAP-based explanations covering both a direct tree-based explanation and a quantum surrogate. Reporting followed the TRIPOD + AI guideline. Results: On the internal test partition, RBF-SVM achieved the highest discrimination (AUC = 0.998), with XGBoost, LightGBM, CatBoost, the hybrid ensemble, and the VQC clustering between 0.992 and 0.996; the QSVM with a ZZ-fidelity kernel underperformed substantially (AUC = 0.727). Pairwise tests for correlated ROC curves indicated that most differences among top models were not statistically significant. On the external WBC cohort, model rankings reorganised, as RBF-SVM (AUC = 0.986, 95% CI 0.946–0.997), RandomForest (0.985, 95% CI 0.945–0.996), VQC (0.983, 95% CI 0.942–0.995), and the hybrid ensemble (0.982, 95% CI 0.941–0.995) all retained near-ceiling discrimination with extensively overlapping confidence intervals. Ablation analysis demonstrated that the choice of embedding rotation is decisive—Z-rotation embeddings collapsed VQC performance to chance levels (AUC ≈ 0.50), whereas X- and Y-rotations preserved it. Depolarising noise up to p = 0.10 had a negligible effect on the VQC, and SHAP analyses converged on worst concave points, mean concave points, and worst area as the dominant predictors across both classical and quantum models. Decision curve analysis showed positive net benefit for both classical and hybrid models across the clinically meaningful threshold range, exceeding both the treat-all and treat-none reference strategies throughout. Conclusions: In the present regime, the principal contribution of QML is not raw discrimination—modern classical learners are already at the data ceiling—but the construction of a rigorous, reproducible, externally validated, and interpretable benchmarking framework in which quantum models can be fairly compared with their classical counterparts. Because evaluation was confined to curated benchmark datasets rather than real-world clinical populations, the interpretability and net benefit findings reported here should be read as benchmark-level evidence and not as a demonstration of readiness for clinical deployment.
Background: Breast cancer remains a leading cause of cancer-related mortality, and reliable computational decision support is increasingly viewed as a complement to expert pathological assessment rather than a replacement for it. Variational quantum classifiers (VQCs) and Quantum Support Vector Machines (QSVMs) have recently been promoted as candidate models for medical classification, yet most published comparisons rely on internal hold-out validation alone and report only a single point estimate of discrimination, omitting calibration, decision-analytic value, and explainability—three ingredients that any clinically credible model must furnish. Methods: We assembled a complete quantum–classical machine learning pipeline and evaluated it under a deliberately stringent protocol designed to expose, rather than conceal, the limitations of current Noisy Intermediate-Scale Quantum (NISQ)-era models. The analytical hypothesis was conservative and stated in advance; in light of saturated classical baselines on this benchmark, we did not anticipate a quantum advantage in raw discrimination, and we framed the study as a methodological probe rather than as a competition. Using the Wisconsin Diagnostic Breast Cancer (WDBC) dataset (n = 569) for development and an independent Wisconsin Original (WBC) cohort (n = 683) for external validation, we benchmarked five classical learners (XGBoost, LightGBM, CatBoost, RandomForest, RBF-SVM), two quantum models (an eight-qubit VQC implemented in PennyLane and a ZZ-feature-map QSVM implemented in Qiskit), and a stacked hybrid ensemble. The evaluation framework combined Optuna-driven hyperparameter optimisation, internal–external cross-validation, and external validation on the independent WBC cohort. Robustness and interpretability were then probed through circuit depth and embedding rotation ablation, depolarising noise stress tests, learning curve and feature stability analysis, decision curve analysis, and dual SHAP-based explanations covering both a direct tree-based explanation and a quantum surrogate. Reporting followed the TRIPOD + AI guideline. Results: On the internal test partition, RBF-SVM achieved the highest discrimination (AUC = 0.998), with XGBoost, LightGBM, CatBoost, the hybrid ensemble, and the VQC clustering between 0.992 and 0.996; the QSVM with a ZZ-fidelity kernel underperformed substantially (AUC = 0.727). Pairwise tests for correlated ROC curves indicated that most differences among top models were not statistically significant. On the external WBC cohort, model rankings reorganised, as RBF-SVM (AUC = 0.986, 95% CI 0.946–0.997), RandomForest (0.985, 95% CI 0.945–0.996), VQC (0.983, 95% CI 0.942–0.995), and the hybrid ensemble (0.982, 95% CI 0.941–0.995) all retained near-ceiling discrimination with extensively overlapping confidence intervals. Ablation analysis demonstrated that the choice of embedding rotation is decisive—Z-rotation embeddings collapsed VQC performance to chance levels (AUC ≈ 0.50), whereas X- and Y-rotations preserved it. Depolarising noise up to p = 0.10 had a negligible effect on the VQC, and SHAP analyses converged on worst concave points, mean concave points, and worst area as the dominant predictors across both classical and quantum models. Decision curve analysis showed positive net benefit for both classical and hybrid models across the clinically meaningful threshold range, exceeding both the treat-all and treat-none reference strategies throughout. Conclusions: In the present regime, the principal contribution of QML is not raw discrimination—modern classical learners are already at the data ceiling—but the construction of a rigorous, reproducible, externally validated, and interpretable benchmarking framework in which quantum models can be fairly compared with their classical counterparts. Because evaluation was confined to curated benchmark datasets rather than real-world clinical populations, the interpretability and net benefit findings reported here should be read as benchmark-level evidence and not as a demonstration of readiness for clinical deployment.
Breast cancer is rated as one of the top leading diagnosed and deadliest cancers affecting women worldwide and causing high mortality rate among cancers. With the data-driven applications, hybrid quantum-classical machine learning models have evolved as significant alternatives for handling complex feature spaces with the growing interest in quantum computing. This paper presents a systematic comparative study of classical and quantum machine learning approaches for breast cancer classification using the Wisconsin Breast Cancer Dataset. In this architecture we have preprocessed classical feature vectors using standard normalized techniques and parallelly quantum states are mapped through data embedding techniques which relies on parameterized rotational gates. In this work we have implemented all quantum models using the Pennylane library, resulting in hybrid quantum–classical optimization on near-term quantum simulators. The comparison results in multiple classical and quantum models. In classical we have Support Vector Machine (SVM), K-Nearest Neighbors (KNN) and Convolutional Neural Networks (CNN), which are compared with the quantum-based models such as the Variational Quantum Classifier (VQC), Quantum Support Vector Machine (QSVM) and Quantum Convolutional Neural Network (QCNN). In QSVM, we have performed dimensionality reduction using Principal Component Analysis (PCA) before to quantum embedding, and quantum-generated features are used to train a classical linear SVM. The evaluation metrics results in accuracy, precision, recall, F1-score, ROC curves and confusion matrices. The classical models achieves the accuracy in the range of 94%-96%, whereas competitive performance of quantum models demonstrate depending on the embedding strategy and circuit configuration. In the implemented quantum models, the variational quantum classifier achieved the highest classification accuracy of 96.06%, surpassing other evaluated models. These results demonstrate quantum embedding combined with variational quantum circuits can effectively capture discriminative patterns in medical datasets, indicating the implementation of quantum machine learning models for breast cancer diagnosis with the present quantum simulating platforms.
In recent years, quantum machine learning (QML) has emerged as a promising approach for medical decision-making, with representative methods such as Quantum Support Vector Machines (QSVMs), Quantum Neural Networks (QNNs), and Variational Quantum Circuits (VQCs). Among these, VQCs are distinguished by their expressive capability; however, their training on small biomedical datasets often results in instability and high variance. To address this issue, we propose a heterogeneous ensemble of six shallow VQCs evaluated on the Wisconsin Breast Cancer Diagnostic (WBCD) dataset, which contains 569 diagnostic samples characterized by 30 cytological features and binary class labels differentiating benign and malignant cases. The ensemble introduces diversity through distinct feature maps, circuit architectures, and optimization strategies, using rotation gates (RX, RY, RZ) combined with entangling layers (CNOT, CZ). Model reliability is estimated from out-of-bag errors, with normalized weights calculated as the inverse of the mean squared error, and final decisions obtained via weighted soft voting. The preprocessing pipeline involves median imputation and standardization, followed by principal component analysis (PCA) to compress the 30-dimensional space into three to four principal components for quantum encoding. In our experiments, individual VQCs trained on the full dataset exhibited unstable accuracies ranging from 80% to 96% across three–four qubits, whereas the proposed ensemble achieved consistent performance of 95.71% (3 qubits) and 96.43% (4 qubits), reducing variance and matching strong classical baselines such as SVM and Random Forest. All models were implemented in PennyLane, utilizing the Lightning.qubit simulator for shot-free optimization and the default.mixed device for noise-aware evaluation, demonstrating the potential of weighted quantum ensembles for reliable biomedical classification.
Breast cancer continues to be among the most common causes of cancer death globally, with early and precise diagnosis playing a pivotal role in enhancing patient survival. Traditional machine learning (ML) techniques have shown great promise in the field of medical imaging and diagnosis; however, the emergence of quantum machine learning (QML) offers new avenues for the improvement of pattern discovery and diagnostic accuracy in high-dimensional medical data. This work describes a thorough benchmark comparison of quantum and classical machine learning methods for breast cancer diagnosis over the Wisconsin Diagnostic Breast Cancer data and mammographic image data. We compare variational quantum classifiers (VQC), quantum kernel methods (QKM), quantum convolutional neural networks (QCNNs), and hybrid quantum-classical neural structures with traditional classical baselines like support vector machines (SVM) and convolutional neural networks (CNN). QKM techniques perform better in high-dimensional feature spaces and better generalize on external validation sets. This implementation framework describes in depth how to develop, train, and deploy QML models in the clinical workflow, including optimization approaches, code structures, and deployment issues. The work demonstrates that it is possible to streamline breast cancer screening and diagnosis using QML with more accurate and more efficient solutions, which would lead to a huge impact on patient outcomes.
Quantum assisted machine learning (QML) have the potential to outperform the classical Machine Learning models by utilizing the quantum feature maps embeddings and variational circuits. In this study, a Hybrid Quantum Support Vector Machine (QSVM) and Quantum Neural Network (QNN) is proposed for supervised classification applied to the Breast Cancer Wisconsin Dataset. The QSVM component employs fidelity quantum kernels with three distinct feature maps—Z, ZZ and Pauli—to transform classical data into quantum states. The QNN is implemented using a variational quantum classifier based on the EstimatorQNN, which enables quantum-trainable parameters for enhanced feature extraction. The proposed hybrid methodology is evaluated using seven principal features, and experiments are conducted on IBM’s state vector Qiskit Aer local simulator. Performance is assessed based on accuracy, recall, precision, F1-score, and confusion matrix. Additionally, statistical significance is evaluated using paired t test and F test to compare the performance of different quantum feature maps and to validate improvements made in the Hybrid Model. The results demonstrate that the hybrid QSVM/QNN approach improves classification performance not only in terms of accuracy by achieving above 90% accuracy but also by reducing computational cost. This work contributes to the advancement of quantum enhanced machine learning (ML) algorithms by demonstrating the hybrid quantum-classical approach in structured data classification.
Introduction: In recent years, high-dimensional clinical and genomic data have gained significant importance for prognosis and personalized medicine in breast cancer. But the use of quantum machine learning (QML) on such data is limited by the availability of few qubits, the computation time of quantum simulation, and dimensionality reduction. This work systematically compares several QML architectures for breast cancer classification in the presence of realistic and simulator constraints. Methods: The experiments were performed on a dataset of METABRIC breast cancer patients (2,509 patients). After handling missing values and one-hot encoding, there were 63 features in the processed data set. The feature space was reduced by Principal Component Analysis (PCA) to 12, 4 and 2 components for the implementations of quantum computers, respectively, with 56.10 ± 0.14%, 26.78 ± 0.57% and 16.23 ± 0.33% of the variance retained. Three QML models were tested: Quantum Neural Networks (QNN), Quantum K-Nearest Neighbors (QKNN), and Quantum Support Vector Machines (QSVM), with the models being simulated. Seven classical classification models were tested: Logistic Regression, SVM with RBF kernel, K-Nearest Neighbors, Random Forest, XGBoost, LightGBM and Multilayer Perceptron, both with PCA-matched and full 63-feature representation. All primary results are reported with 5-fold cross validation. Results: Among the evaluated QML architectures, QKNN using 12 principal components achieved the strongest performance, attaining an accuracy of **75.11% ± 3.76%**, an F1-score of **0.7088 ± 0.0433**, and a ROC-AUC of **0.8148 ± 0.0394**. Even though all of the QML models performed significantly poorly in comparison to classical models trained on the entire 63-feature data set, the latter models were able to achieve about **94% accuracy** with XGBoost, Random Forest, and Logistic Regression. The comparison also showed the effect of information loss due to PCA is significant in predictive performance in both classical and quantum models. Discussion: The results show that for high dimensional breast cancer data, currently available simulator-based QML models can learn meaningful patterns with limited quantum resources, but are not as effective as powerful classical machine learning models when complete feature representations are available. The study does not report any sort of quantum advantage or clinical use, but rather a benchmark of current QML architectures that has been rigorously calculated and repeated, with a focus on the impact of dimensionality reduction, validation approaches, and simulator limitations, as well as outlining challenges that need to be overcome prior to practical implementation on real quantum hardware.
Variational quantum classifiers (VQCs) are often compared with classical models under unequal data partitions, tuning budgets, or statistical treatment. We benchmark a 4-qubit VQC against logistic regression, an RBF-SVM, random forest, a quantum-kernel SVM (QSVM), and a majority-class control on Breast Cancer Wisconsin (n=569), Coimbra (n=116), and Golub leukemia (n=72), using five stratified folds across five seeds (25 paired blocks per dataset), identical training-fold-fitted preprocessing, and Nadeau–Bengio corrected paired tests with Holm correction. A first arm with a frozen configuration and the common [0, π] angle encoding left the VQC at 0.563, 0.515, and 0.576 accuracy (majority 0.617, 0.552, 0.652). In a second arm, in which every model was tuned by the same inner cross-validation and the encoding scale was a tuned hyperparameter, VQC accuracy rose to 0.864, 0.616, and 0.747. On Wisconsin the VQC stayed significantly below every matched classical model (differences 0.079–0.097, Holm p≤0.006) but above the majority class; on Golub it was significantly below only the SVM (Holm p=0.016); on Coimbra no comparison was significant. A QSVM with the same feature map exceeded the VQC numerically on every dataset, and three optimizers reached the same training loss in pilot diagnostics, pointing to the encoding and the variational head rather than the optimizer. The Wisconsin arms also differ in sample size (120 versus 569). Results apply to this low-qubit, PCA-compressed, exactly simulated setting and do not indicate a quantum advantage.