Pretreatment DCE-MRI Resolves Response Quality Within Pathologic Endpoints in Neoadjuvant Breast Cancer

Pathologic complete response (pCR) is a strong neoadjuvant endpoint, yet 5-15% of complete responders recur and clinical/genomic variables do not reliably identify them. We tested whether pretreatment dynamic contrast-enhanced MRI entropy - intratumoral enhancement heterogeneity - resolves response quality hidden within pCR and residual cancer burden (RCB). Across four cohorts (1,200 patients), a prespecified entropy threshold defined favorable and adverse structural states. Crossing structure with pathology yielded a four-tier framework spanning 4.1-fold recurrence in I-SPY1 and 7.7-fold at response extremes. In I-SPY2, 55 of 219 complete responders (25.1%) were structurally adverse, pretreatment. In an external HER2-positive responder synthesis (I-SPY1 pathology-confirmed pCR plus UCSF best-response proxy; n = 33, 10 events), adverse structure was associated with higher recurrence risk (HR = 2.87, 95% CI 1.38-5.96) capturing 7 of 10 recurrences, enriching rather than determining risk. In a HER2-positive RCB-0 subset, recurrence was 12.5% with favorable and 80.0% with adverse structure; Firth Cox regression preserved the association (HR = 8.13, 95% CI 1.71-49.21; n = 21, 6 events). In Duke (n = 908; 76 events), favorable structure remained independently associated with lower distant-recurrence risk (adjusted HR = 0.61, 95% CI 0.41-0.91). RNA linked favorable structure to a directionally reproduced immune-architecture program among non-overlapping patients within ISPY2; EMT-pathway enrichment was favorable-side, while the adverse tier contained a broadly immune-depleted substate. Yet full-cohort RNA models weakly discriminated structural state and did not recover continuous entropy. Pretreatment MRI therefore does not replace pCR or RCB; it reveals response-quality differences that these endpoints compress and identifies a recurrence-enriched group for prospective validation.

MagViT: Interpretable Multi-Magnification Transformers with Patient-Level Model Selection for Breast Histopathology

Breast cancer is one of the most common types of cancer among women around the world. Rapid detection and early treatment can hinder its progress to more complex stages and can impede its spread to other parts of the body. Histopathological image classification is the most common task in cancer detection due to its robustness in analyzing cellular data. Breast histopathology classification requires handling both multi-scale tissue morphology and clinically relevant generalization beyond the source domain. This paper presents MagViT, an interpretable multi-magnification transformer framework with scale-gated fusion and patient-level model selection. The model uses four BreakHis magnifications (40X, 100X, 200X, 400X) and extracts per-scale representations with a ViT backbone, and combines them via a learnable gate that masks missing scales. Patient-level five-fold cross-validation with a fixed seed has been run and compared with three architectural branches. The most accurate branch is then selected as the final model due to the strongest patient-level accuracy while retaining the simplest fusion pathway. On BreakHis, our architecture achieves a mean image accuracy of 0.9191, a mean patient accuracy of 0.9643, and a mean macro-F1 of 0.9042. External transfer experiments provide preliminary evidence of cross-dataset generalization under controlled adaptation settings on BUSI (image accuracy 0.8306, macro-F1 0.7480, patient accuracy 0.8291) and IDC (image accuracy 0.8577, macro-F1 0.8191, patient accuracy 0.8372). Grad-CAM visualization indicates that the model focuses on diagnostically significant and meaningful regions across magnifications. Relative to prior ViT-centered BreakHis work, this study emphasizes patient-level selection and cross-dataset robustness under a reproducible protocol.

Clinical Feasibility of Low-Magnification Fluorescence Imaging for Breast Cancer Margin Detection Using Texture Analysis and Deep Learning

High-resolution images of unprocessed surgical breast tissue can be obtained using microscopy with ultraviolet surface excitation (MUSE). This technique is considered a promising method for checking surgical margins during breast cancer surgery. In this study, MUSE images at 4x and 10x magnifications were compared using patch-level classification methods. Texture analysis (TA) based on local binary patterns (LBP) and deep learning (DL) with a base Vision Transformer (ViT) model were used. Both methods achieved similar performance at both magnifications. Using DL method, both 4x and 10x magnifications achieved 96.30% sensitivity, 100% specificity and 98.18% accuracy. Using TA method, 4x achieved better specificity (100% vs 93.33%) and 10x yielded higher sensitivity (100% vs 93.33%), but both had the same accuracy (96.67%). No clear improvement in performance was observed with 10x magnification. These results show that 4x imaging achieves the same diagnostic accuracy as 10x imaging. At the same time, 4x offers a larger field of view and faster image capture. Therefore, lower magnification can be effectively used in MUSE systems for accurate and efficient intraoperative margin assessment.

Pre- to Post-Contrast Synthesis of Breast DCE-MRI using Latent Bridge Matching

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is central to breast cancer imaging, but gadolinium administration increases scan burden and motivates contrast-reduced alternatives, including synthetic contrast generation. We propose a latent bridge matching (LBM) framework for synthesizing peak-enhanced breast DCE-MRI from pre-contrast images in the MAMA-SYNTH challenge setting. Instead of starting from Gaussian noise as in conventional latent diffusion models (LDMs), the proposed model learns a conditional bridge between paired pre-contrast and peak-enhanced VAE latents. A latent UNet predicts the remaining correction from intermediate bridge states to the peak-enhanced latent, enabling iterative refinement while keeping the trajectory anchored to patient-specific anatomy. We evaluated two LBM conditioning variants on 91 DUKE validation cases. For the tumor-conditioned variant, tumor masks were used as conditioning inputs. Tumor-conditioning improved performance compared with pre-contrast conditioning, reducing MSE from 1.023 to 0.940 and FRD from 7.523 to 4.716, while increasing tumor SSIM from 0.355 to 0.429. The tumor-conditioned LBM also outperformed the evaluated LDM baseline on this validation cohort. These results suggest that latent bridge matching is a promising pre-contrast-anchored formulation for virtual contrast enhancement, while further work is needed to validate generalization and remove dependence on ground-truth tumor masks at inference.

Longitudinal 3D Foundation Modeling for Neoadjuvant Breast Cancer Response Prediction from Serial DCE-MRI

Pathologic complete response (pCR) is an important endpoint in neoadjuvant chemotherapy (NAC) for breast cancer, and predicting pCR from imaging during treatment could support treatment response assessment. Many existing imaging-based approaches rely on a single static timepoint, which fails to capture changes that occur during treatment. In this work, we present a longitudinal framework that combines a frozen 3D foundation encoder (Pillar-0) with our Temporal Dynamics Network (TDN) to predict treatment response from serial Dynamic Contrast-Enhanced (DCE) MRI acquired across four clinical timepoints from pre-treatment to pre-surgery. The TDN combines time-aware volumetric embeddings with clinical and treatment data to predict pCR. Evaluated on 982 patients from the combined I-SPY2 and ACRIN-6698 cohort, the proposed model achieves strong performance across all reported metrics when longitudinal 3D imaging is fused with clinical data (test AUROC: 73.6%, balanced accuracy: 69.1%). While clinical variables provide the strongest individual predictive signal, longitudinal 3D imaging contributes complementary information when fused with clinical data, improving pCR prediction. Our source code is available at: https://github.com/omarftt/longitudinal_temporal_pillar.

Harnessing Adversarial Distillation to Customise Debiased, Disease-Specific Pathology Foundation Models for Breast Cancer

Pathology foundation models (PFMs) provide strong tissue representations and have become central to digital pathology. However, deployment in disease-specific settings is limited by 1) the high computational cost of billion-parameter PFMs and 2) distribution mismatch and non-biological bias inherited from pan-cancer, multi-centre pre-training, including site-specific signatures and imbalanced disease prevalence. These factors can encourage shortcut learning and under-emphasise subtle morphology required for reliable modelling of a specific cancer type. We present SmartStu (a Smart Student), a framework to customise compact, breast-cancer-specific PFMs via distillation whilst mitigating confounding. SmartStu distils representations from multiple teacher PFMs into a lightweight student backbone. Crucially, we introduce adversarial distillation that leverages a dedicated noise model trained to predict nuisance, edge-dominated cues on the distillation set. Using this noise model as a counterexample, the adversarial objective encourages the student to recognise, yet suppress, features predictive of nuisance targets. We further incorporate multi-teacher ensemble distillation and an auxiliary self-supervised objective with artefact injection. We validate SmartStu on three external cohorts (Yale HER2, SLN-Breast, and BRACS) with multiple tiny backbones. SmartStu yields breast-cancer-specific PFMs that are over $30\times$ smaller than general PFMs whilst largely preserving, and sometimes improving, downstream performance measured by balanced accuracy (bAcc) and AUC. Code is available at https://github.com/zwchen03/advDistall.

Dense Temporal Contrast Synthesis via Conditioned Latent Transport

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is essential for breast cancer management, but reliance on gadolinium-based contrast agents (GBCAs) restricts use in contraindicated populations, prolongs scan protocols, and presents environmental toxicity concerns. Contrast synthesis offers a non-invasive alternative; however, existing approaches struggle to balance spatial realism with temporal continuity, suffer from slow iterative sampling, underutilize structural priors, and lack clinical validation. We propose a novel conditioned latent transport framework that predicts contrast enhancement in a single forward pass. By anchoring the latent trajectory to the pre-contrast anatomy and applying continuous time conditioning, the model synthesizes patient-specific contrast evolution at any acquisition time. The proposed approach outperforms baseline and the state-of-the-art models across spatial, perceptual, temporal, and distributional metrics. Evaluated on an independent external cohort, the method demonstrates robustness to domain shifts induced by scanner noise as well as differing acquisition protocol. Furthermore, our synthetic contrast enhancement significantly improved downstream tumor segmentation performance, yielding a 22.4% relative increase in Dice coefficient (0.60 vs. 0.49 baseline pre-contrast, p < 0.01), reducing boundary segmentation error by over 39%, while outperforming all other generative model baselines. Finally, a reader study involving four breast radiologists evaluated the image quality, kinetic fidelity, and diagnostic viability of our synthesized sequences across 40 randomly selected cases. The results demonstrated that in 70% of cases, synthesized images provided sufficient clinical information to support the same management decisions as real DCE-MRI, suggesting a path toward safer and faster contrast-free or contrast-reduced imaging workflows.

What Carries the Signal in Pathology Foundation-Model Atlases? A Patient-Level Controlled Benchmark in Breast Cancer

Pathology foundation models are reported to encode molecular programmes in tissue morphology, but the evidence is usually a cohort-wide ranked gene list rather than a prediction for a held-out patient. We rebuild such an analysis with the patient as the unit of evidence and ask which pipeline component carries signal. Across 11 frozen backbones, four pre-specified gene programmes and 285 TCGA-BRCA patients with paired slides and RNA-seq (44 cells; GroupKFold by patient, all preprocessing fitted inside the fold), ridge regression on mean-pooled embeddings predicts held-out programme scores at Spearman rho = 0.25-0.56, UNI2 strongest on all four (immune 0.556). A matched permutation null gives raw p ~ 1e-4 at 10,000 permutations for every cell; Holm-adjusted p = 0.0044. The signal is real but not uniformly morphological. Against competing models on the same patients and folds, embeddings beat tissue composition for ER/luminal, proliferation and immune (+0.280, +0.284, +0.479; p <= 0.003) but not basal, where compartment fractions alone reach 0.469 against the embedding's 0.493 (p = 0.77). Fifty-four interpretable cell-count features come within 0.043-0.085 on every programme. The geometric machinery contributes nothing measurable, and we identify why: the geodesic graph selects neighbours by Euclidean nearest-neighbour search and only reweights edges already chosen, so the topology is Euclidean by construction (Riemannian minus Euclidean = +0.0010, 95% CI [-0.0007, +0.0029]). Applied consistently the geometry is worse (-0.0117). Ridge regression beats the graph-and-metric decoder by +0.097 (CI [+0.069, +0.127]). The driver-count metric common in this literature is near-uninformative here: 91.8% of random six-gene panels recover >=5/6 drivers.

Superpixel-Based QUBO for Scalable Quantum-Enhanced Medical Image Segmentation

Quadratic unconstrained binary optimization (QUBO) has emerged as a powerful framework for medical computing problems. Binary decision variables naturally represent clinical choices, making QUBO formulations well-suited for quantum annealing hardware. However, a fundamental scalability challenge limits practical deployment: problem size grows rapidly with input dimensionality, creating computational bottlenecks that restrict applications to simplified scenarios. This paper addresses this challenge through hierarchical problem reduction, as demonstrated in medical image segmentation, where pixel-level QUBO formulations create over 65,000 variables for a 256x256 image, forcing existing approaches to downsample to 42x42 resolution and discard 97% of pixel information. A superpixel-based QUBO framework is proposed using simple linear iterative clustering (SLIC) to group pixels into perceptually meaningful regions, then formulate segmentation as QUBO over a region adjacency graph (RAG) combining min-cut and smoothness objectives. Validation on INbreast mammography breast cancer images demonstrates a 4.2% improvement in segmentation quality (mean IoU 0.76 vs 0.73) with 33 computational speedup (0.67s vs 21.97s) and a 97.3% reduction in problem size (1764 to 48 variables), all achieved while processing full-resolution images rather than downsampled versions. The reduced problem size also fits well within current quantum annealer connectivity limits, removing the embedding overhead that has historically blocked direct deployment of pixel-level QUBO segmentation on quantum hardware.

An unsupervised clustering analysis of breast cancer data derived from electronic health records enhanced through UMAP dimensionality reduction

Breast cancer is one of the most widespread types of cancer, affecting approximately 8 million women worldwide. Electronic health records of patients diagnosed with this disease can serve as valuable datasets for computational analyses, enabling the discovery of new insights about the pathology. Unsupervised clustering, in particular, can identify groups of patients with medically significant features, revealing data trends that might otherwise go unnoticed by medical doctors. In this study, we first applied the DBSCAN density-based clustering method to three independent datasets derived from electronic medical records of patients with mammary carcinoma. Subsequently, to enhance our results, we preceded the DBSCAN application with a dimensionality reduction phase using UMAP. We evaluated our clustering outcomes using three statistical indices (DBCV, DCSI, and DISCO). Our results confirm the effectiveness of combining UMAP with DBSCAN for clustering data derived from electronic health records, paving the way for the medical interpretation of the patient groups identified by our approach.

Agentic systems for breast cancer treatment recommendations

Large language models (LLMs) are increasingly being explored for clinical decision support, but their reliability in complex oncology treatment planning remains unclear. We evaluated agentic LLM systems for breast cancer treatment recommendation generation using 72 real clinical cases across stages I to IV and 1,147 case-specific rubrics generated through Asymmetric Information Rubric Generation (AIRG), in which the rubric generator had access to real clinical decisions unavailable to the evaluated models. Seven pipelines were compared, including single-LLM baselines, tool-augmented systems, and multi-agent architectures with fact checking and autonomous subagent spawning. The best-performing configuration, Claude Opus 4.8 with the D&C+SA pipeline, achieved a global score of 0.594 $\pm$ 0.025. Tool use and increased agent autonomy had mixed effects, improving performance in some settings but degrading it in others. Performance varied by clinical domain and disease stage, and oncologist-led error analysis revealed persistent clinically relevant failures, including incorrect or missing recommendations, flawed justifications, citation errors, outdated claims, and overconfidence. These findings suggest that agentic LLM systems can generate clinically relevant breast cancer recommendations, but remain insufficient for unsupervised clinical use.

BiLoG-Net: A Bi-Context Location-Guided Network for Breast Mass Segmentation and Malignancy Classification in Mammography

Breast cancer remains the most commonly diagnosed malignancy among women worldwide, yet accurate detection and characterization of breast masses in mammography remain challenging due to subtle intensity variations, heterogeneous tissue densities, and indistinct lesion boundaries that complicate radiological interpretation. To address these limitations, we propose BiLoG-Net, a deep learning framework that jointly performs breast mass segmentation and malignancy classification through bi-context location-aware feature modeling and segmentation-guided attention mechanisms. Our architecture integrates a novel encoder-decoder paradigm with Fire-based feature extraction, lightweight global and local feature enhancement modules, and adaptive location-aware gating to simultaneously capture long-range contextual dependencies and fine-grained boundary-sensitive details. Unlike conventional multi-stage pipelines, our tightly coupled multi-task design enables mutual reinforcement between pixel-level localization and image-level diagnosis, reducing error propagation while producing spatially grounded malignancy predictions. Evaluated on CBIS-DDSM and INBreast benchmarks, BiLoG-Net achieves state-of-the-art performance with Dice scores of 94.20% and 93.10%, classification accuracies of 95.20% and 93.60%, and AUC values of 97.10% and 96.00%, respectively, substantially outperforming existing CNN and transformer-based baselines. By combining precise boundary delineation with reliable malignancy assessment in a single end-to-end model, this work holds strong potential for clinical computer-aided detection systems, helping radiologists prioritize suspicious cases and improve screening efficiency in busy clinical settings.

Token-Based Dual-view Fusion and Adaptation of Large Vision Models for Breast Cancer Classification

Accurate breast cancer classification from mammography requires effective integration of complementary information from craniocaudal (CC) and mediolateral oblique (MLO) views, which provide a more complete characterization of breast abnormalities. However, existing multi-view learning approaches typically rely on feature-level aggregation or single-stage cross-attention, which can entangle view-specific and shared representations and restrict interaction to limited network depths. To address these limitations, we propose a token-centric dual-view learning framework that unifies prompt-based adaptation and cross-view fusion within a frozen vision transformer backbone. The framework reformulates inter-view interaction as structured token-level communication, where dedicated fusion tokens explicitly encode bidirectional information exchange between CC and MLO views via cross-attention, serving as intermediate carriers of cross-view dependencies rather than relying on direct feature fusion. Unlike conventional methods that apply fusion at a single layer, fusion modules are inserted at multiple transformer depths, enabling progressive and repeated interaction across the encoder hierarchy. Fusion tokens are reintegrated into the token sequence and refined by subsequent transformer layers, facilitating hierarchical propagation of complementary information while preserving view-specific structure. Experiments on VinDr-Mammo and CMMD datasets demonstrate consistent improvements over linear probing, prompt-only adaptation, and conventional fusion baselines. On the VinDr-Mammo BI-RADS classification task, the framework achieves 50.40% F1-score and 0.8090 AUC, including a 0.10 AUC improvement over a dual-view fusion baseline in the binary setting. Ablation studies further validate the effectiveness of token-based fusion and multi-depth interaction design.

Graph Representation Learning of Longitudinal Medical Imaging Trajectories for Treatment Response Prediction

In patients with breast cancer, pathological complete response (pCR) has been established as a clinically meaningful surrogate marker for long-term outcomes. While commonly treated with neoadjuvant chemotherapy (NACT), effective treatment decision-making remains challenging, as therapeutic response can vary substantially across patients, calling for predictive models capable of accurately estimating individualized treatment response. To address this, we propose an imaging-based 3D spatio-temporal framework for treatment response prediction that integrates a state-of-the-art graph neural network with relational modeling of temporal interactions across timepoints alongside three novel complementary self-supervised treatment trajectory representation learning objectives. Experiments across a cohort of 585 patients from the public ISPY-2 dataset demonstrate that our method substantially outperforms both vision and self-supervised learning baselines across several classification metrics. Alongside establishing a breast cancer pCR prediction benchmark, we include a principled ablation of our method and further introduce and empirically assess the impact of the available number of DCE-MRI timepoints per patient trajectory and the inclusion of inter-scan time-differences. Overall, our study substantiates the utility of clinically meaningful longitudinal medical imagaging modeling for predicting NACT-induced pCR. We will publicly share our code repository and a user-friendly PyPI library for dataset curation upon publication, effectively promoting reproducible open-source research.

Pretreatment MRI reveals a latent, molecular-subtype-independent structural phenotype that organizes treatment trajectories and recurrence risk

Pathologic complete response and tumor shrinkage measure whether breast cancer responds to neoadjuvant therapy, but not whether that response was structurally favorable, persistent, or hidden beneath volume loss. We built an outcome-blind longitudinal DCE-MRI manifold from I-SPY2 trajectories to test whether pretreatment imaging carries a structural response phenotype missed by conventional descriptors. The dominant axis of response geometry was not recoverable from the full clinical and genomic stack -- age, receptor subtype, MammaPrint, PAM50, treatment arm, and tumor burden -- but became strongly recoverable once baseline structural entropy was added. A constrained representation mapping recovered the same axes as unconstrained decomposition, establishing the structure as intrinsic rather than a post-hoc interpretation. The phenotype persisted through therapy, and as treatment proceeded the volumetric signal faded while entropy stayed separated -- a crossover from burden to structural persistence. Among complete responders, structurally disordered tumors could shrink more early yet remain structurally disordered, a volumetric deception invisible to endpoint labels. External analyses in UCSF, I-SPY1, and Duke established recurrence relevance under representation-dependent boundaries, and a representation-family commensurability assessment showed why feature-name matching is insufficient: the same label can fail, transport, or entangle with extraction geometry. Pretreatment MRI therefore exposes a structural response phenotype that endpoint-based language leaves invisible -- including, among complete responders, a pretreatment imaging signal of structurally distinct response states that awaits prospective validation.

ClinRAG-GRAPH: Clinical-prior Retrieval-Augmented Graph Model with Domain Adversarial Learning for Breast pCR Prediction

Neoadjuvant chemotherapy (NAC) response prediction is clinically important for treatment stratification in breast cancer. However, robust pre-treatment pathological complete response (pCR) prediction remains challenging due to insufficient cross-modal modeling, multicenter imaging heterogeneity, and weak evidence-grounded interpretability. We propose ClinRAG-GRAPH, a Clinically informed Retrieval-Augmented Generation Graph framework, for pre-treatment pCR prediction from DCE-MRI, structured clinical variables, and biopsy-derived pathological biomarkers. ClinRAG-GRAPH constructs an intra-patient clinical-prior graph and applies a prior-guided relation-aware graph convolutional network for structured multimodal representation learning. To improve cross-center robustness, we introduce a dual-branch domain-adversarial learning strategy to suppress protocol-related MRI bias while preserving pCR-relevant features. To enhance interpretability, we further incorporate large language model (LLM)-driven subgraph RAG module that retrieves clinically analogous historical cases and integrates retrieved evidence for pCR inference. We assemble a large-scale multicenter NAC breast cancer cohort for extensive validation, drawing from two public sources and three in-house centers.Results show that ClinRAG-GRAPH achieves AUCs of 0.815 on the internal test set and 0.774/0.712 on two external test sets, demonstrating robust pre-treatment pCR prediction across centers. The code is available at the anonymized https://github.com/miccai26-1181/ClinRAG-GRAPH.

A Multi Center Breast FNAC Whole-Slide Cytology Dataset for AI-Assisted Patch-Wise Classification Using C1 to C5 Reporting Categories

We present a multi center breast fine needle aspiration cytology (FNAC) dataset designed for patch wise classification using C1 to C5 reporting labels. The prospective dataset includes 321 patients and 470 whole-slide images (WSIs) collected from participating tertiary medical centers in India between May 2023 and March 2026. Slides were stained using Papanicolaou (190 WSIs) or MayGrunwald Giemsa (280 WSIs), scanned on a Hamamatsu NanoZoomer S360 at 40X magnification and 0.25 microns per pixel, and stored directly in NDPI format. Across the 470 WSIs, 446 WSIs contain annotated patch regions, yielding 7,398 PNG image patches with expert-verified C1 to C5 labels. The release includes NDPI WSIs, WSI-level GeoJSON annotation files, extracted patch images, deidentified metadata, a data dictionary, a validation summary, a manifest linking WSIs to Zenodo records, and code for dataset inspection and reuse. The complete dataset is approximately 950 GB and is available through Zenodo.

Benchmarking Machine Learning Models for Multi-Omics-Based Breast Cancer Prediction

Estrogen Receptor (ER) status is a critical biomarker in breast cancer diagnosis, prognosis, and treatment selection. Recent advances in high-throughput sequencing technologies have enabled the generation of multi-omics datasets that provide complementary molecular information for computational prediction tasks. This study presents a systematic benchmarking analysis of classical machine learning models for ER status prediction using transcriptomic (RNA expression), genomic (copy number variation; CNV), and proteomic (RPPA) data from the TCGA-BRCA cohort. A rigorous experimental framework incorporating stratified train-test splitting, stratified five-fold cross-validation, class imbalance handling, and fold-specific feature selection was employed to ensure reliable evaluation and prevent data leakage. Random Forest, XGBoost, LightGBM, CatBoost, Support Vector Machines (SVM), and Logistic Regression were evaluated across single-omic and multi-omic settings. Results demonstrated that RNA expression provided the strongest predictive signal, while multi-omic integration yielded modest but consistent improvements over individual modalities. Among all evaluated approaches, Random Forest achieved the best overall performance in the integrated multi-omic setting, obtaining a balanced accuracy of 90.3\% and an ROC-AUC of 97.1\%. Furthermore, recurrent selection of biologically relevant genes, including \textit{ESR1}, \textit{PGR}, \textit{FOXA1}, and \textit{GATA3}, supported the biological validity of the learned models. These findings indicate that carefully regularized classical machine learning methods remain highly effective for small, high-dimensional genomic datasets and that multi-omic integration provides complementary information for breast cancer ER status prediction.

JASPR: Joint Spatial Representation learning of histology and spatial genomics for improved virtual genomic screening and clinical prognostication

Recent studies have shown that spatial properties of tumors are critical for understanding disease biology and predicting patient outcomes. These spatial properties are increasingly uncovered through complementary modalities: spatial transcriptomics (ST) captures spatially-resolved molecular states, while hematoxylin and eosin-stained whole slide images (HE) reveal tissue morphology. While approaches are emerging to fuse these modalities, effective methods that learn not only joint representations but also incorporate spatial context across modalities are lacking. Here, we present JASPR (Joint Spatial Representation learning), a self-supervised deep learning framework that integrates HE images and ST data through a cross-modal reconstruction objective that incorporates spatial context within HE images and ST profiles. It employs shared modules to capture universal spatial properties across modalities, while modality-specific experts encode features unique to morphological and genomic data. We train and validate JASPR on breast cancer datasets, demonstrating that its learned joint representation substantially improves HE-based prediction of 9,248 genes and provides prognostic value for breast cancer outcomes.

Federated Survival Analysis in Healthcare: A Multi-Model Evaluation on Cross-Institutional Heterogeneous Breast Cancer Data

Survival analysis is central to clinical decision-making, yet reliable time-to-event models require large, diverse cohorts that are rarely available at a single institution, while privacy regulations restrict the centralization of patient data. Federated learning (FL) offers a privacy-preserving alternative by training shared models without exchanging raw data, but its effectiveness for survival modeling under realistic, heterogeneous conditions remains insufficiently understood. This paper presents a systematic, multi-model evaluation of federated survival analysis on a cross-institutional breast cancer cohort with naturally heterogeneous distributed clients. Three representative survival models, the Cox Proportional Hazards model, DeepSurv, and Random Survival Forest (RSF), are compared across centralized, local, and federated training, and three federated optimization strategies (FedAvg, FedProx, and FedAdam) are assessed for the gradient-based models. Results show that FL consistently outperforms local training and approaches, and occasionally exceeds, centralized performance, while RSF offers the best overall balance of discrimination, calibration, and robustness across heterogeneous clients. We further find that performance depends on the diversity of client distributions, and that FedAvg and FedProx are stronger and more stable than FedAdam. Based on these findings, we derive practical, decision-oriented guidelines mapping data, privacy, interpretability, and resource constraints to recommended model and training-paradigm choices for federated survival modeling in healthcare.

HERO: Hypothesis-Driven Evidence Retrieval from Omics for Multi-Task Breast Cancer Analysis

Matched multi-omics can improve WSI-based biomarker and prognosis prediction, but most existing pipelines use omics as a paral lel feature stream or textual context rather than as an explicit retrieval constraint. HERO asks whether observed omics can be a testable mor phology hypothesis: a sparse pathway-to-morphology prior maps DNA methylation and miRNA into a K-dimensional intent vector m (K=16), TF-IDF retrieval over structured 10 captions selects endpoint-relevant regions, and a cosine gate c=cos(m,v) triggers deterministic deficit driven repair when c<τc. This closed-loop design bounds VLM calls, reduces reliance on embedding-based semantic matching, and makes every retrieval and verification step lexically auditable. On TCGA-BRCA (930WSIs, patient-level 5-fold CV), HERO sets new state-of-the-art across ER, PR, HER2, subtype, and risk prediction, outperforming both multimodal fusion and VLM-based baselines.

MammoExpert: Benchmarking Chain-of-Thought Reasoning in Mammography Diagnosis

Mammography is an essential tool for breast cancer detection, with millions of examinations conducted annually. However, publicly available high-quality mammography datasets for AI development remain limited in both scale and annotation richness, particularly regarding pathological subtype coverage and structured diagnostic reasoning annotations. In this paper, we present MammoExpert, the first mammography dataset with Chain-of-Thought reasoning annotations across three diagnostic phases: (i) primal observation, (ii) factual assessment, and (iii) diagnostic synthesis. Comprising 2,379 mammography images covering 67 WHO-classified histopathology subtypes, each exam provides 42 radiographic features annotated by nine senior radiologists. We evaluate its performance on the breast lesion classification task, demonstrating superior accuracy and reasonability compared to existing classification models. Combining public dataset CBIS-DDSM with MammoExpert yields 7.1\% classification accuracy improvement, while the training model to learn CoT reasoning achieves another 4\% gain on the MammoExpert test set. Similar improvements are observed on INBreast and Vindr datasets, where the full approach yields accuracy gains of 6.9\% and 6.7\%, respectively. MammoExpert can serve as a benchmark for interpretable breast lesion diagnosis through explicit CoT reasoning.

DSU-Net: An Attention-Enhanced Dense Skip U-Net for Breast Lesion Segmentation in Mammographic Images

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, making early detection essential for effective treatment. Mammography is the primary screening modality; however, accurate delineation of suspicious lesions remains challenging and subject to inter-observer variability. Automated segmentation methods can assist radiologists by providing consistent and efficient lesion localization. This study presents DSU-Net, an attention-enhanced Dense Skip U-Net architecture for automated breast lesion segmentation in mammographic images. The proposed framework integrates dense skip connections and attention mechanisms to improve feature propagation, preserve spatial information, and enhance lesion boundary delineation. Experiments were conducted using the Curated Breast Imaging Subset of the Digital Database for Screening Mammography (CBIS-DDSM). To address severe foreground-background imbalance, a composite loss function combining Dice loss, focal loss, and binary cross-entropy loss was employed during training. The proposed model achieved a Dice Similarity Coefficient of 0.9421, an Intersection over Union of 0.8905, an accuracy of 0.9711, and an AUC-ROC of 0.9878 on the validation dataset. Qualitative evaluation demonstrated accurate delineation of lesions with varying sizes and morphologies, while quantitative results confirmed robust discrimination between lesion and background regions. These findings demonstrate that DSU-Net provides accurate and reliable breast lesion segmentation in mammographic images and highlights the potential of attention-guided deep learning for computer-aided breast cancer screening and diagnosis.

BreastGPT: A Multimodal Large Language Model for the Full Spectrum of Breast Cancer Clinical Routine

Breast cancer remains a leading cause of cancer-related mortality among women. Its clinical management requires multimodal reasoning across a clinical workflow that spans \textit{screening}, \textit{diagnosis} and \textit{treatment planning}, where each stage involves distinct imaging modalities, task objectives, and reasoning patterns. However, constrained by data scarcity and model versatility, existing medical MLLMs are typically evaluated on isolated modalities or narrow task families, limiting their ability to support workflow-level clinical reasoning. In this work, we first introduce \textbf{BreastStage}, a workflow-aligned breast imaging instruction corpus comprising 1.86M instruction-following pairs curated from 17 sub-datasets across 5 imaging modalities and 136 task templates. Its held-out split, \textbf{BreastStage-Bench}, provides a comprehensive benchmark for evaluating multimodal reasoning across the breast cancer care continuum. Building on this corpus, we propose \textbf{BreastGPT}, a unified MLLM equipped with a dual-branch visual encoder and concept-preserving token compression to bridge the scale gap between standard radiology and gigapixel pathology. On BreastStage-Bench, BreastGPT achieves 75.66\% closed-ended accuracy and 89.92\% open-ended score, outperforming both general-purpose and medical-specific MLLMs across clinical stages and task formats. These results suggest that workflow-aligned data and cross-scale visual modeling are critical for clinically grounded medical MLLMs. All data, code, and model checkpoints are released at https://yangyy-liu.github.io/BreastGPT.io.

Multi-Modal Machine Learning for Breast Cancer Recurrence Prediction

Breast cancer recurrence, a leading cause of long-term mortality among survivors, requires timely and accurate risk assessment to guide follow-up care and treatment planning. Traditional predictive models, often limited to either structured or unstructured data alone, struggle to capture the full clinical context. This study examines the impact of integrating multi-modal clinical data, including treatment records, pathology reports, and clinician notes, on recurrence prediction. By integrating a rule-based regular expression extraction mechanism with a rigorous precedence-based conflict reconciliation strategy, our approach effectively recovers definitive tumor characteristics from free-text pathology narratives to augment structured records. We also benchmark performance against commonly used feature sets from prior breast cancer studies to assess the added value of multi-modal integration. Single-source and multi-modal inputs are evaluated across a range of machine learning models. Results show that multi-modal integration consistently improves predictive accuracy compared to single-modal methods.

Benchmarking Pathology Foundation Models for Breast Cancer Survival Prediction

Pathology foundation models (PFMs) have recently emerged as powerful pretrained encoders for computational pathology, enabling transfer learning across a wide range of downstream tasks. However, systematic comparisons of these models for clinically meaningful prediction problems remain limited, especially in the context of survival prediction under external validation. In this study, we benchmark widely used and recently proposed PFMs for breast cancer survival prediction from whole-slide histopathology images. Using a standardized pipeline based on patch-level feature extraction and a unified survival modeling framework, we evaluate model representations across three independent clinical cohorts comprising more than 5,400 patients with long-term follow-up. Models are trained on one cohort and evaluated on two independent external cohorts, enabling a rigorous assessment of cross-dataset generalization. Overall, H-optimus-1 achieves the strongest survival prediction performance. More broadly, we observe consistent generational improvements across model families, with second-generation PFMs outperforming their first-generation counterparts. However, absolute performance differences between many recent PFMs remain modest, suggesting diminishing returns from further scaling of pretraining data or model size alone. Notably, the compact distilled model H0-mini slightly outperforms its larger teacher model H-optimus-0, despite using fewer than 8% of the parameters and enabling significantly faster feature extraction. Together, these results provide the first large-scale, externally validated benchmark of PFMs for breast cancer survival prediction, and offer practical guidance for efficient deployment of PFMs in clinical workflows.