Search Results (177)

The year 2025 has been transformative in breast oncology, marked by the maturation of pivotal adjuvant trials, the introduction of novel ADCs, and the validation of proactive biomarker-driven strategies across all molecular subtypes. ASCO, ESMO, and SABCS contributed pivotal updates that further refined treatment paradigms. This systematic review synthesizes and critically evaluates pivotal Phase II/III clinical trials presented at major oncology conferences (ASCO 2025, ESMO 2025, SABCS 2025) and published in high-impact journals during 2025. A curated selection of pivotal Phase II/III trials, and major prospective trials published or presented in 2025 was performed. Data extraction focused on trial design, population, interventions, efficacy endpoints, and safety outcomes. Narrative synthesis was organized by disease stage and molecular subtype. Key 2025 findings (50 clinical trials) include: (1) confirmation of overall survival benefit with adjuvant CDK4/6 inhibitors in HR+/HER2− early breast cancer (monarchE: HR = 0.842, p = 0.0273); (2) establishment of trastuzumab deruxtecan (T-DXd) as a new standard in high-risk HER2+ early disease (DESTINY-Breast05: IDFS HR = 0.47) and first-line metastatic settings (DESTINY-Breast09: PFS HR = 0.58); (3) validation of TROP2-directed ADCs as first-line therapy for metastatic triple-negative breast cancer (ASCENT-03: PFS HR = 0.62; BEGONIA: ORR 79%); (4) paradigm shift to proactive, liquid biopsy-guided therapy switching (SERENA-6: PFS HR = 0.44); (5) updated efficacy and safety of the oral SERD imlunestrant from the EMBER-3 trial, supporting its role in ESR1-mutated advanced breast cancer and in combination with abemaciclib; (6) confirmation of long-term survival benefit for neoadjuvant carboplatin in early TNBC and new positive adjuvant data; (7) pivotal advances in HER2+ metastatic disease sequencing with tucatinib and T-DXd; (8) evidence supporting optimized adjuvant endocrine therapy in HER2+/HR+ early disease; and (9) emergence of novel agents with improved therapeutic indices, including PROTAC degraders, oral SERDs, and mutant-selective PI3K inhibitors. The 2025 evidence base has fundamentally reshaped breast cancer management, establishing new standards of care across all subtypes. Unifying themes include biomarker-driven personalization, strategic treatment sequencing, management of unique toxicities, and emphasis on patient-reported outcomes. Future challenges include optimizing treatment integration, managing financial toxicity, and ensuring equitable global access. Full article

High-speed electrical wireline links, spanning Serializer/Deserializer backplanes and cables, chip-to-chip and die-to-die interfaces, wide-parallel single-ended (SE) buses, and simultaneous-bidirectional (SBD) buses, increasingly operate under severe insertion loss, long channel memory, and strong multi-lane interference. Equalization is therefore a central enabler for reliable symbol recovery in the presence of inter-symbol interference (ISI), echo, and near-/far-end crosstalk. This review synthesizes recent principles, architectures, and silicon-proven implementations of wireline equalizers with an emphasis on practical hardware constraints. It further organizes key research trajectories in high-speed wireline communications across three domains: (i) Time-domain equalization and detection for ISI-limited channels, spanning feed-forward equalizers, latency-relaxed decision-feedback equalization architectures that mitigate stringent feedback-loop constraints, and partial-response signaling combined with reduced-complexity maximum-likelihood sequence detection to enhance resilience against extended channel memory. (ii) Advanced modulation and frequency-domain processing, marking the transition from conventional 4-level pulse-amplitude modulation toward higher-order constellations and multicarrier techniques, notably discrete multitone and orthogonal frequency-division multiplexing, which necessitates modulation-aware frequency-domain equalization and adaptive bit- and power-loading algorithms. (iii) Crosstalk and echo mitigation for dense SE and SBD systems, including cancellation filtering in a multiple-input multiple-output framework and coding-aided interference suppression approaches. Across these domains, we present the fundamental trade-offs between equalization performance, algorithmic convergence, power-area efficiency, and latency. Full article

Antibody–drug conjugates (ADCs) have reshaped the treatment landscape of urothelial carcinoma (UC) by enabling selective delivery of highly potent cytotoxic agents to tumor cells. Enfortumab vedotin, sacituzumab govitecan, and HER2-directed ADCs have demonstrated meaningful clinical activity across metastatic and earlier disease settings, with enfortumab vedotin plus pembrolizumab now established as a first-line standard of care. Despite these advances, therapeutic responses remain heterogeneous, and resistance frequently limits durability. This review summarizes current knowledge on predictors of response and mechanisms of resistance to ADCs in UC, highlighting the roles of target antigen expression and heterogeneity, genomic alterations, payload sensitivity, drug efflux transporters, and tumor microenvironmental factors. We discuss emerging biomarkers beyond antigen abundance, patterns of cross-resistance and treatment sequencing, and evolving strategies to overcome resistance, including next-generation ADC design and rational combination therapies. Advancing biomarker-driven patient selection and addressing mechanisms of resistance will be critical to maximizing the durability and clinical impact of ADCs in urothelial carcinoma. Full article

Background/Objectives: The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is characterized by an enriched stroma, hampering the effectiveness of therapy. This co-clinical study aimed to (1) provide insight into early post-treatment changes in the TME using multiparametric magnetic resonance imaging (mpMRI)-derived quantitative imaging biomarkers (QIBs) in a preclinical PDAC model treated with radiotherapy and correlate these QIBs with histology; (2) evaluate the feasibility of obtaining these QIBs in patients with PDAC using clinically approved mpMRI data acquisitions. Methods: Athymic mice (n = 12) at pre- and post-treatment as well as patients with PDAC (n = 11) at pre-treatment underwent mpMRI including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) data acquisition sequences. DW and DCE data were analyzed using monoexponential and extended Tofts models, respectively. DeepLIIF quantified the total percentage (%) of tumor cells in hematoxylin and eosin (H&E)-stained tissues from athymic mice. Spearman correlation and Wilcoxon signed rank tests were performed for statistical analysis. Results: In the preclinical PDAC model, mean pre- and post-treatment ADC and K^trans values differed significantly (p < 0.01), changing by 20.50% and 20.41%, respectively, and the median total tumor cells quantified by DeepLIIF was 24% (range: 15–53%). Post-treatment ADC values and relative change in v_e (rΔv_e) showed a significant negative correlation with total tumor cells (ρ = −0.77, p < 0.014 for ADC and ρ = −0.77, p = 0.009 for rΔv_e). In patients with PDAC, pre-treatment mean ADC and K^trans values were 1.76 × 10⁻³ (mm²/s) and 0.24 (min⁻¹), respectively. Conclusions: QIBs in both preclinical and clinical settings underscore their potential for future co-clinical research to evaluate emerging drug combinations targeting both tumor and stroma. Full article

The clinical significance of perivascular spaces (PVS) remains controversial. Radiomics refers to the extraction of quantitative features from medical images using pixel-based computational approaches. This study aimed to compare the radiomics features of normal-appearing white matter (NAWM) in patients with low and high PVS scores to reveal microstructural differences that are not visible macroscopically. Adult patients who underwent cranial MRI over a one-month period were retrospectively screened and divided into two groups according to their global PVS score. Radiomics feature extraction from NAWM was performed at the level of the centrum semiovale on FLAIR and ADC images. Radiomics features were selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression during the initial model development phase, and predefined radiomics scores were evaluated for both sequences. A total of 160 patients were included in the study. Radiomics scores derived from normal-appearing white matter demonstrated good discriminative performance for differentiating high vs. low perivascular space (PVS) burden (AUC = 0.853 for FLAIR and AUC = 0.753 for ADC). In age- and scanner-adjusted multivariable models, radiomics scores remained independently associated with high PVS burden. These findings suggest that radiomics analysis of NAWM can capture subtle white matter alterations associated with PVS burden and may serve as a non-invasive biomarker for early detection of microvascular and inflammatory changes. Full article

Background: Magnetic resonance imaging (MRI) plays an increasingly important role in the evaluation of scrotal and penile disorders, complementing ultrasonography in cases where findings are equivocal or complex. With its superior soft-tissue contrast, multiplanar capability, and advanced functional sequences, MRI provides unparalleled anatomic and tissue characterization across a wide range of male genital pathologies. Summary: This review summarizes current clinical applications of MRI in scrotal and penile imaging and discusses its diagnostic value, protocol optimization, and interpretive features. In scrotal pathology, MRI accurately differentiates torsion, trauma, infection, and neoplasms, aiding in the distinction between benign and malignant testicular lesions and supporting testis-sparing management. Quantitative diffusion and perfusion metrics further refine lesion characterization. In andrology, MRI biomarkers such as apparent diffusion coefficient (ADC), magnetization transfer ratio (MTR), and proton spectroscopy serve as promising non-invasive indicators of spermatogenic activity in male infertility. In penile imaging, MRI enables precise local staging of carcinoma, assessment of plaque morphology and activity in Peyronie’s disease, evaluation of tissue viability in priapism, and detection of prosthesis-related complications. Conclusions: MRI has become an essential problem-solving tool in the assessment of scrotal and penile diseases, enhancing diagnostic confidence and surgical planning. Future directions include protocol standardization, quantitative parameter validation, and the integration of radiomics and artificial intelligence to improve reproducibility and clinical impact. Full article

Background/Objectives: This study aimed to evaluate the diagnostic accuracy of Apparent Diffusion Coefficient (ADC) values, derived from Diffusion-Weighted Imaging (DWI), in differentiating benign and malignant ascites. Methods: This retrospective study included 150 patients (85 benign, 65 malignant) who underwent abdominal MRI. All patients were scanned on a DWI sequence (b-values: 0, 500, and 1000 s/mm²). Two experienced radiologists, blinded to clinical and cytological outcomes, measured the mean ADC (ADCmean) from three distinct ROIs and the minimum ADC (ADCmin) from the area of lowest signal intensity on the ADC map. The diagnostic performance of ADC parameters and the Serum-Ascites Albumin Gradient (SAAG) was assessed using Receiver Operating Characteristic (ROC) curve analysis. Results: The mean values of ADCmean (3162 ± 204 × 10⁻⁶ mm²/s) and ADCmin (2885 ± 148 × 10⁻⁶ mm²/s) in the malignant group were significantly lower than those in the benign group (3596 ± 239 and 3322 ± 218 × 10⁻⁶ mm²/s; p = 0.006 and p = 0.0016, respectively). Inter-observer agreement was good for both ADCmean (ICC = 0.844) and ADCmin (ICC = 0.879). In the ROC analysis, ADCmin demonstrated the highest diagnostic performance (AUC: 0.930). An optimal cut-off value for ADCmin of ≤ 2983 × 10⁻⁶ mm²/s yielded 81.5% sensitivity and 85.8% specificity. The diagnostic performance of ADCmin was found to be superior to that of ADCmean (AUC: 0.877) and SAAG (AUC: 0.919). Conclusions: ADC values derived from DWI, particularly ADCmin, represent a highly accurate, non-invasive, and reproducible biomarker for differentiating benign from malignant ascites. The identified ADCmin threshold provides quantitative parameter that can aid in patient triage, especially when cytology is inconclusive, potential surrogate for fluid characterization. Full article

Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor marked by diffuse infiltration into surrounding brain tissue. The peritumoral zone often appears normal on imaging yet harbors microscopic invasion. While perfusion-based studies, such as arterial spin labeling (ASL), have profiled this region, longitudinal radiomic monitoring remains limited. This study investigates delta radiomics using multiparametric MRI (mpMRI) in a GBM mouse model to track subtle peritumoral changes over time. Methods: A G7 GBM xenograft model was established in nine nude mice, imaged at 9- and 12 weeks post-implantation using MRI (T1W, T2W, T2 mapping, DWI-ADC, FA, and ASL) and co-registered histopathology (H&E, HLA staining). Tumor and peritumoral regions were manually segmented, and 107 radiomic features (shape, first-order, texture) were extracted per sequence and histology. The delta features were calculated and compared between timepoints. Results: The robust T2W texture and T2 map first-order features demonstrated the greatest sensitivity and reproducibility in capturing temporal peritumoral brain zone changes, distinguishing between time points used by K-mean. Conclusions: Delta radiomics offers added value over static analysis for early monitoring of peritumoral brain zone changes. The first-order and texture features of radiomics could serve as robust biomarkers of peritumoral invasion. These findings highlight the potential of longitudinal MRI-based radiomics to characterize glioblastoma progression and inform translational research. Full article

Therapies targeting human epidermal growth factor receptor 2 (HER2) have substantially improved overall survival in patients with HER2-positive metastatic breast cancer. Approximately 31% of these patients develop brain metastases, representing a significant therapeutic challenge. This review classifies anti-HER2 therapies into three categories: monoclonal antibodies (MABs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The mechanisms of action and clinical impacts of these agents are examined, with particular attention to intracranial efficacy. The introduction of trastuzumab increased overall survival (OS) from 20.3 to 25.1 months compared to chemotherapy alone. The addition of pertuzumab further extended survival to 57.1 months, as demonstrated in the CLEOPATRA trial. Among ADCs, T-DM1 improved OS to 29.9 months versus 25.9 months in the EMILIA trial, while T-DXd extended OS to 52.6 months in DESTINY-Breast03. T-DXd also demonstrated notable intracranial activity, achieving a 64.9% objective response rate in patients with active brain metastases. In the HER2CLIMB trial, tucatinib reduced intracranial progression by 68% and improved OS (24.7 vs. 19.2 months) in patients with active brain metastases. Recent advances have increased median OS from approximately 20 months prior to trastuzumab to over 50 months with current therapies. Future research should focus on optimizing treatment sequencing, refining biomarker-driven approaches, and developing targeted strategies for brain metastases to further improve long-term survival outcomes. Full article

Background/Objectives: The therapeutic landscape of advanced or metastatic urothelial carcinoma (UC) has shifted from platinum chemotherapy to precision immuno-oncology. Immune checkpoint inhibitors (ICIs)—pembrolizumab, nivolumab, and avelumab—show efficacy across platinum-refractory, maintenance, and adjuvant settings, yet benefit is limited to subsets, underscoring the need for biomarkers. Antibody–drug conjugates (ADCs), notably enfortumab vedotin(EV), and targeted agents such as FGFR inhibitors further expand options. This review synthesizes current evidence and emerging paradigms to guide combinations and sequencing. Methods: We performed a narrative synthesis of peer-reviewed trials (emphasizing pivotal phase III studies), key translational investigations, and contemporary guidelines on ICIs, ADCs, HER2-directed therapies, FGFR inhibitors, molecular subtyping, and genomic profiling in UC, integrating efficacy signals, biomarker associations, and practical implications for sequencing. Results: ICIs now occupy multiple settings, but heterogeneous benefit highlights the importance of molecularly informed selection. EV alone and with pembrolizumab has produced unprecedented first-line activity, prompting a strategic shift. Molecular subtyping and genomic profiling delineate phenotypes with variable immune responsiveness and targetable vulnerabilities, enabling rational combinations and refined sequencing. Ongoing trials are evaluating next-generation ADCs, HER2-directed approaches, and dual checkpoint blockade to achieve durable, personalized disease control. Conclusions: Management of locally advanced or metastatic UC is converging on precision immuno-oncology, wherein biomarker-driven selection, molecular subtyping, and thoughtful sequencing of ICIs, ADCs, and targeted agents are central to optimizing outcomes. Active trials and translational advances are expected to refine personalized strategies and embed molecular guidance into routine care. Full article

Background: Antibody-drug conjugates (ADCs) have ushered in a new era of precision oncology by combining the targeting specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs. However, the cellular and molecular mechanisms underlying their dose-limiting ocular toxicity remain unclear. Elahere™, the first FDA-approved ADC targeting folate receptor α (FRα), demonstrates remarkable efficacy in platinum-resistant ovarian cancer but causes keratitis and other ocular toxicities in some patients. Notably, FRα is not expressed in the corneal epithelium—the primary site of damage—highlighting the urgent need to elucidate its underlying mechanisms. The aim of this study was to identify the cell-type-specific molecular mechanisms underlying Elahere-induced ocular toxicity. Methods: Sprague-Dawley rats were treated with intravenous Elahere (20 mg/kg) or vehicle weekly for five weeks. Ocular toxicity was determined by clinical examination and histopathology. Corneal single-cell suspensions were analyzed using the BD Rhapsody single-cell RNA sequencing (scRNA-seq) platform. Bioinformatic analyses to characterize changes in corneal cell populations, gene expression, and signaling pathways included cell clustering, differential gene expression, pseudotime trajectory inference, and cell-cell interaction modeling. Results: scRNA-seq profiling of 47,606 corneal cells revealed significant damage to the ocular surface and corneal epithelia in the Elahere group. Twenty distinct cell types were identified. Elahere depleted myeloid immune cells; in particular, homeostatic gene expression was suppressed in phagocytic macrophages. Progenitor populations (limbal stem cells and basal cells) accumulated (e.g., a ~2.6-fold expansion of limbal stem cells), while terminally differentiated cells decreased in corneal epithelium, indicating differentiation blockade. Endothelial cells exhibited signs of injury and inflammation, including reduced angiogenic subtypes and heightened stress responses. Folate receptor alpha, the target of Elahere, was expressed in endothelial and stromal cells, potentially driving stromal cells toward a pro-fibrotic phenotype. Fc receptor genes were predominantly expressed in myeloid cells, suggesting a potential mechanism underlying their depletion. Conclusions: Elahere induces complex, multi-compartmental ocular toxicity characterized by initial perturbations in vascular endothelial and immune cell populations followed by the arrest of epithelial differentiation and stromal remodeling. These findings reveal a cascade of cellular disruptions and provide mechanistic insights into mitigating Elahere-associated ocular side effects. Full article

Accurate preoperative staging of bladder cancer on MRI remains challenging because visual reads vary across observers. We investigated a multiparametric MRI (mpMRI) radiomics approach to predict muscle invasion (≥T2) and prospectively tested it on a validation cohort. Eighty-four patients with urothelial carcinoma underwent 1.5-T mpMRI per VI-RADS (T2-weighted imaging and DWI-derived ADC maps). Two blinded radiologists performed 3D tumor segmentation; 37 features per sequence were extracted (LifeX) using absolute resampling. In the training cohort (n = 40), features that differed between non-muscle-invasive and muscle-invasive tumors (Mann–Whitney p < 0.05) underwent ROC analysis with cut-offs defined by the Youden index. A compact descriptor combining GLRLM-LRLGE from T2 and GLRLM-SRLGE from ADC was then fixed and applied without re-selection to a prospective validation cohort (n = 44). Histopathology within 6 weeks—TURBT or cystectomy—served as the reference. Eleven T2-based and fifteen ADC-based features pointed to invasion; DWI texture features were not informative. The descriptor yielded AUCs of 0.934 (training) and 0.871 (validation) with 85.7% sensitivity and 96.2% specificity in validation. Collectively, these findings indicate that combined T2/ADC radiomics can provide high diagnostic accuracy and may serve as a useful decision support tool, after multicenter, multi-vendor validation. Full article

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of infectious disease mortality worldwide. Global TB control efforts face several hurdles, including the lack of a broadly effective vaccine, limited sensitivity of current diagnostics, particularly for paucibacillary and extrapulmonary TB, and significant adverse effects associated with prolonged small-molecule drug regimens. The growing prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains further underscores the urgent need for innovative therapeutic strategies. We outline characteristics of next-generation TB therapeutics. We show that antibody (Ab)-drug conjugates (ADCs) satisfy many of those desirable characteristics. Since a major hurdle to this approach lies in Mtb-specific Abs, we highlight an open-access resource comprising a broad panel of Mtb-specific mouse monoclonal antibodies targeting key factors involved in Mtb survival, immune evasion, and pathogenesis. These critical Mtb virulence factors include heat shock proteins (GroES, DnaK, and HspX), surface-associated or secreted proteins (LAM, Ag85, HBHA, Mpt64/CFP-21, and PhoS1/PstS1), cell wall/envelope-associated proteins (LprG/p27), and detoxifying enzymes (KatG and SodA). The resource provides full-length sequences of the immunoglobulin variable regions, enabling antibody engineering and facilitating translational TB research across vaccine design, diagnostic development, and immunotherapeutic applications, in addition to ADCs. This ADC targeted delivery strategy holds promise for overcoming TB heterogeneity and eliminating both active and dormant Mtb populations within a single therapeutic formulation and offers a novel avenue for precision TB treatment. Full article

The 2021 WHO classification of brain tumours revolutionised the oncological field by emphasising the role of molecular, genetic and pathogenetic advances in classifying brain tumours. In this context, incidental gliomas have been increasingly identified due to the widespread performance of standard and advanced MRI sequences and represent a diagnostic and therapeutic challenge. The impactful decision to perform a surgical procedure deeply relies on the non-invasive identification of features or parameters that may correlate with brain tumour genetic profile and grading. Therefore, it is paramount to reach an early and proper diagnosis through neuroradiological techniques, such as MRI. Standard MRI sequences are the cornerstone of diagnosis, while consolidated and emerging roles have been awarded to advanced sequences such as Diffusion-Weighted Imaging/Apparent Diffusion Coefficient (DWI/ADC), Perfusion-Weighted Imaging (PWI), Magnetic Resonance Spectroscopy (MRS), Diffusion Tensor Imaging (DTI) and functional MRI (fMRI). The current novelty relies on the application of AI in brain neuro-oncology, mainly based on radiomics and radiogenomics models, which enhance standard and advanced MRI sequences in predicting glioma genetic status by identifying the mutation of multiple key biomarkers deeply impacting patients’ diagnosis, prognosis and treatment, such as IDH, EGFR, TERT, MGMT promoter, p53, H3-K27M, ATRX, Ki67 and 1p19. AI-driven models demonstrated high accuracy in glioma detection, grading, prognostication, and pre-surgical planning and appear to be a promising frontier in the neuroradiological field. On the other hand, standardisation challenges in image acquisition, segmentation and feature extraction variability, data scarcity and single-omics analysis, model reproducibility and generalizability, the black box nature and interpretability concerns, as well as ethical and privacy challenges remain key issues to address. Future directions, rooted in enhanced standardisation and multi-institutional validation, advancements in multi-omics integration, and explainable AI and federated learning, may effectively overcome these challenges and promote efficient AI-based models in glioma management. The aims of our multidisciplinary review are to: (1) extensively present the role of standard and advanced MRI sequences in the differential diagnosis of iLGGs as compared to HGGs (High-Grade Gliomas); (2) give an overview of the current and main applications of AI tools in the differential diagnosis of iLGGs as compared to HGGs (High-Grade Gliomas); (3) show the role of MRI, radiomics and radiogenomics in unravelling glioma genetic profiles. Standard and advanced MRI, radiomics and radiogenomics are key to unveiling the grading and genetic profile of gliomas and supporting the pre-operative planning, with significant impact on patients’ differential diagnosis, prognosis prediction and treatment strategies. Today, neuroradiologists are called to efficiently use AI tools for the in vivo, non-invasive, and comprehensive assessment of gliomas in the path towards patients’ personalised medicine. Full article

Background: Muscle-invasive bladder cancer (MIBC) is associated with high recurrence and mortality rates. While cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy remains the standard of care, many patients are ineligible for cisplatin. Recent advances in immunotherapy and biomarker research are reshaping perioperative strategies, aiming to personalize treatment and improve outcomes. Methods: We conducted a comprehensive narrative review of the recent literature and clinical trials on the perioperative treatment of MIBC. We focused on published phase II and III trials assessing neoadjuvant and adjuvant strategies, including immunotherapy, antibody-drug conjugates (ADCs), combination regimens, and circulating tumor DNA (ctDNA)-based approaches. Results: Numerous trials (e.g., PURE-01, ABACUS, NABUCCO, AURA, NIAGARA) have demonstrated the feasibility and efficacy of immune checkpoint inhibitors (ICIs) in both cisplatin-eligible and -ineligible populations. Combination strategies, including ICIs plus chemotherapy or ADCs, have shown promising pathological complete response rates and event-free survival. In the adjuvant setting, nivolumab improved disease-free survival and received regulatory approval. Biomarkers such as PD-L1 and ctDNA are emerging tools for predicting treatment response and recurrence risk, although prospective validation is ongoing. Conclusions: The treatment paradigm for MIBC is shifting toward multimodal and biomarker-driven approaches. Integration of ICIs into perioperative management, especially in combination with chemotherapy or ADCs, may enhance outcomes. ctDNA shows potential as a predictive and prognostic biomarker, guiding therapeutic decisions and surveillance. Future research should focus on refining patient selection, optimizing treatment sequencing, and validating ctDNA-guided strategies to personalize care while minimizing overtreatment. Full article