Search Results (1,560)

Background: Neoadjuvant chemoimmunotherapy is now a standard approach for resectable stage II–III non-small cell lung cancer (NSCLC), demonstrating improved pathological response and survival. However, its safety in physiologically high-risk surgical patients is unclear, as these groups are underrepresented in trials. This study compares 30-day and 90-day mortality and oncological outcomes of neoadjuvant chemoimmunotherapy followed by surgery versus upfront surgery within a high-risk multidisciplinary team (MDT) cohort. Methods: A retrospective single-centre study was performed, including consecutive high-risk MDT patients undergoing resection for stage II -III NSCLC between January 2022 and December 2025. High-risk status was defined by established physiological, cardiopulmonary, and comorbidity criteria. Patients were stratified into neoadjuvant chemoimmunotherapy followed by surgery (Chemo-IO; n = 33) or upfront surgery (n = 57). The primary outcome was 30-day mortality. Secondary outcomes included 90-day mortality, R0 resection rate, and length of hospital stay. Inverse probability of treatment weighting (IPTW) based on propensity scores was used to balance baseline differences between groups. Results: Ninety patients were included. Patients receiving neoadjuvant therapy had a greater comorbidity burden (Charlson Comorbidity Index 3.2 ± 1.5 vs. 1.4 ± 1.7, p < 0.001) and more advanced disease (stage III: 57.6% vs. 29.8%, p = 0.014). Thirty-day mortality was 0% in the Chemo-IO group and 1.8% following upfront surgery. After IPTW adjustment, neoadjuvant therapy was not associated with increased perioperative mortality. Ninety-day mortality was similar between groups (3.0% vs. 3.5%; IPTW OR 0.91, 95% CI 0.05–15.39, p = 0.948). R0 resection rates were numerically higher following Chemo-IO (87.9% vs. 78.9%; IPTW OR 3.42, 95% CI 0.71–16.59, p = 0.127). Median hospital stay was identical in both cohorts (6 days), with no significant difference after weighting (p = 0.722). Conclusions: Neoadjuvant chemoimmunotherapy appears safe and feasible in carefully selected high-risk patients with resectable stage II–III NSCLC. Despite greater comorbidity burden and more advanced disease, short-term perioperative outcomes were not compromised, while a trend towards improved R0 resection rates was observed. These findings support the consideration of multimodal treatment strategies within high-risk MDT pathways. Full article

Background: Immune-checkpoint blockade (ICB) is a recent addition to the treatment options for breast cancer, especially the triple-negative (TNBC) subset. Inhibiting immunosuppressive factors in the tumor microenvironment (TME) and preventing or reversing T cell exhaustion may increase the likelihood of a response to ICB. We have shown that decitabine and guadecitabine, DNA methyltransferase inhibitors (DNMTi), prevent the systemic and TME accumulation of myeloid-derived suppressor cells (MDSCs), which are immunosuppressive. Results: Here, we show that adding DNMTi to the neoadjuvant + adjuvant ICB-based treatment of ICB-resistant 4T1 and E0771 murine tumors in Balb/C and C57Bl/6 mice, respectively, effectively reduced the tumor burden, with 52% of 4T1 tumors completely regressing across several studies. DNMTi-based therapy overcame ICB resistance (ICBR) in a selected subline of E0771, and treated tumors showed a reduction in MDSCs. We also show that, in E0771, DNMTi can overcome ICBR to multiple checkpoint inhibitors, and in 4T1, it can modulate anti-tumor immunity by enhancing central memory T cell (Tcm) formation and reducing T cell exhaustion. Conclusion: These pre-clinical findings support the further investigation of incorporating DNMTi as a new immunotherapy modality for TNBC. Full article

Background: Germline PALB2 variants are associated with hereditary breast cancer risk, but their clinical impact in Central Asian populations remains largely uncharacterized. This case study aims to evaluate the clinical significance of PALB2 variants in two Kazakh women with early-onset breast cancer. Methods: Molecular genetic testing identified germline PALB2 pathogenic variants (NM_024675.4:c.18_22delGAAGC and NM_024675.4:c.1034T>G) in two Kazakh women with early-onset invasive ductal carcinoma. Clinical courses, treatment responses, and outcomes were followed. Results: Neither patient had a reported family history of breast or other malignancies. Patient 1, a 26-year-old pregnant woman, was diagnosed with stage IIIB luminal B, HER2-negative invasive ductal carcinoma and received neoadjuvant chemotherapy, radical surgery, radiotherapy, endocrine therapy, and subsequent treatment for metastatic disease. Despite an initial response, she developed extensive skeletal metastases and died from metastatic breast cancer. Patient 2, a 33-year-old woman, presented with de novo stage IV luminal B, HER2-negative invasive ductal carcinoma with hepatic metastases. Following multimodal treatment, including chemotherapy, surgery, radiotherapy, endocrine suppression, and systemic therapy for disease progression, she experienced further metastatic spread and ultimately died from breast cancer-related complications. Conclusions: Both patients exhibited aggressive clinical courses characterized by early disease onset, metastatic progression, and poor outcomes despite comprehensive treatment. These cases highlight the potential clinical significance of germline PALB2 variants in apparently sporadic breast cancer and underscore the importance of genetic testing, risk assessment, and genetic counselling in young breast cancer patients, particularly in underrepresented. Full article

Background/Objectives: Hepatoid adenocarcinoma is a rare adenocarcinoma subtype. Synchronous esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma with hepatoid differentiation is exceptionally uncommon. This report describes lesion-specific staging, pathological response assessment, and individualized management after neoadjuvant chemoimmunotherapy. Methods: De-identified clinical, imaging, laboratory, operative, and pathological data were retrospectively reviewed. Both lesions were staged according to the AJCC 8th edition and reassessed using the CAP modified Ryan four-tier tumor regression grading system. Results: A 61-year-old man presenting with dysphagia had separate ESCC and gastric cardia adenocarcinoma, both staged cT2N0M0. One cycle of pembrolizumab 200 mg, nab-paclitaxel 300 mg, and cisplatin 100 mg was administered. Agranulocytosis precluded further neoadjuvant therapy; after neutrophil recovery, R0 resection was performed. Pathological review showed ESCC ypT1aN0M0, score 1, and cardia adenocarcinoma ypT1aN0M0, score 3, with approximately 30% regional hepatoid differentiation. All 10 examined lymph nodes were negative. AFP was not measured before treatment; post-treatment/preoperative values were 14.45 and 14.68 ng/mL, and the postoperative value was 6.08 ng/mL. Postoperative tislelizumab monotherapy was selected as an individualized, non-standard strategy, mainly because of affordability. At approximately 6 months after surgery, no recurrence, metastasis, or maintenance-related adverse event was identified. Conclusions: This case emphasizes biopsy under-sampling and lesion-specific staging and pathological assessment. The regression-score difference is descriptive and confounded by baseline burden, histology, and one-cycle exposure; the AFP findings do not validate a surveillance biomarker. Full article

Head and neck squamous cell carcinoma (HNSCC) remains a significant global health burden with limited survival improvement in locally advanced disease despite multimodal therapy. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have demonstrated substantial clinical benefit in recurrent or metastatic HNSCC, establishing PD-1 blockade as a standard of care. Similar approaches in locally advanced disease, including concurrent administration with chemoradiotherapy or use in the adjuvant setting, have not demonstrated improvement in survival outcomes across multiple randomized trials. Perioperative strategies incorporating neoadjuvant and adjuvant checkpoint inhibition have shown improved event-free and disease-free survival in resectable disease. Meta-analyses of concurrent and adjuvant approaches confirm limited benefit in unselected populations, with modest improvements restricted to biologically defined subgroups. Trial outcomes across disease settings demonstrate a consistent pattern in which therapeutic efficacy varies despite the use of similar agents. Rather than simply summarizing these clinical findings, this review integrates evidence across recurrent/metatstatic, unresected locally advanced and perioperative disease settings into a biologically focused framework to help explain the varying efficacies of immune checkpoint inhibition in HNSCC. Current evidence indicates that the effectiveness of immunotherapy in HNSCC is determined by the biologic context of treatment, including tumor antigen availability, host immune competence, and timing of immune activation. Administration of checkpoint blockade in the presence of intact tumor antigen and preserved immune function is associated with improved outcomes, whereas treatment delivered during or after cytotoxic therapy is limited by lymphopenia and reduced antigen exposure. By synthesizing randomized clinical evidence through this biologic framework, the review provides a conceptual perspective that may help explain previous trial outcomes and inform future biomarker-driven patient selection and treatment sequencing. Optimization of immunotherapy in HNSCC will depend on the integration of immune activation with disease context rather than an escalation of therapeutic intensity. Full article

Background/Objectives: Deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) colorectal cancer (CRC) are highly sensitive to immune checkpoint blockade. We evaluated the efficacy, safety, and clinical maturity of neoadjuvant PD-1-based immunotherapy in localized disease. Methods: This PRISMA-compliant systematic review included prospective studies of neoadjuvant PD-1-based therapy in localized dMMR/MSI-H CRC. Proportions were pooled on the logit scale using inverse-variance random-effects models with the Paule–Mandel estimator. Pathologic complete response (pCR) was the primary outcome; major pathologic response (MPR), immune-related adverse events (irAEs), surgery, clinical complete response (cCR), organ preservation, and long-term outcomes were secondary outcomes. Results: Five prospective studies were included. Four studies, comprising 305 treated patients and 292 pathologically evaluable patients, contributed five treatment arms to the quantitative synthesis. The pooled pCR proportion was 0.65 (95% CI, 0.54–0.74), and the pooled MPR proportion was 0.89 (95% CI, 0.79–0.94). Exploratory subgroup analyses suggested higher response proportions with combination regimens, but clinical and methodological differences confounded these predominantly indirect comparisons. Any-grade irAEs occurred in 0.54 (95% CI, 0.36–0.71), whereas grade ≥3 irAEs occurred in 0.06 (95% CI, 0.04–0.10). The pooled surgery proportion was 0.96 (95% CI, 0.86–0.99), although this outcome largely reflected protocol-mandated surgery. cCR and organ preservation were promising in selected rectal-cancer cohorts. Survival and recurrence data were immature and unsuitable for quantitative pooling. Conclusions: Neoadjuvant PD-1-based immunotherapy is a highly promising investigational strategy for localized dMMR/MSI-H CRC. Nevertheless, predominantly early-phase evidence, indirect comparisons, heterogeneous endpoints, and limited follow-up preclude definitive conclusions regarding routine clinical adoption. Full article

Background/Objectives: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is an important prognostic marker in HER2-positive breast cancer (BC). However, reliable pre-treatment predictors based on routinely available clinical data remain limited. This study evaluated whether clinicopathologic and baseline magnetic resonance imaging (MRI) variables could predict NAC response using classical machine learning (ML) approaches. Methods: A retrospective cohort of 112 patients with HER2-positive BC treated with NAC was analysed, including 57 patients who achieved pCR and 55 who did not. Fourteen pre-treatment variables were evaluated, including hormone receptor (HR) status, tumour grade, ER and PR expression, Ki67, nodal status, age, and baseline MRI characteristics. Seventy ML classifiers were compared using a fully nested leave-one-out cross-validation (LOOCV) framework. Performance was assessed using accuracy, area under the receiver operating characteristic curve (AUROC), Cohen’s kappa, sensitivity, specificity, and F1-score. Results: A support vector machine (SVM) with a radial basis function (RBF) kernel achieved the highest observed accuracy (82.1%) among the 70 evaluated classifiers. The corresponding AUROC was 83.3%, Cohen’s kappa was 64.2%, and sensitivity, specificity, and F1-score were 87.7%, 76.4%, and 83.3%, respectively. HR-related variables, particularly PR and ER expression, together with Ki67 and baseline MRI features, ranked among the most influential predictors. Despite relying exclusively on routinely available pre-treatment variables, the model demonstrated meaningful predictive performance. Conclusions: ML applied to routinely available clinicopathologic and baseline MRI variables showed promising ability to predict pCR before treatment initiation in HER2-positive BC. The proposed approach may support pre-treatment clinical risk assessment using information already generated during routine clinical assessment. Nevertheless, prospective multicentre external validation, calibration assessment, and evaluation of clinical utility are required before implementation in routine clinical practice. Full article

Breast cancer (BC) can be treated by combinations of surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapies. High-risk patients, including all patients with axillary involved lymph nodes with triple-negative BC (TNBC) and Her2-positive BC, are treated by neoadjuvant chemotherapy (NAC). For high-risk patients, immunotherapy for TNBC, trastuzumab and pertuzumab then trastuzumab deruxtecan for Her2-positive BC have improved survival. In this narrative review, we will discuss therapy for small triple-negative and HER2-positive early BC without involved or suspicious axillary lymph nodes. Upfront surgery is recommended for cT1a-b cN0 usN0 TNBC and Her2-positive BC with adjuvant therapy for pT1b pN0 BC, discussed case by case for pT1a pN0 Her2-positive BC. No adjuvant chemotherapy is considered for pT1a TNBC. However, lymph vascular invasion can also be contributive on pathologic results. For pT1c pN0 TNBC and Her2-positive BC, adjuvant therapy is recommended. For cT2 or cN+ TNBC and Her2-positive BC, NAC is the treatment recommended with adjuvant therapy after surgery according to pathologic results. For cT1c cN0 usN0 TNBC and Her2-positive BC, upfront surgery is the usual treatment proposed but NAC can be strongly considered according to clinic pathologic characteristics, tumor size 10–15 mm or 16–20 mm, grade, young age (≤35-years) and co-morbidities, particularly for elderly patients. Recent tools such as TIL level determined on core needle biopsy may help when considering NAC or upfront surgery and systemic therapy regimens. Other prognostic tools can contribute to the determined therapeutic strategy and systemic therapy regimens with escalation or de-escalation, such as TNBCDX or HER2DX, possibly in combination with TIL level. Full article

Background: Breast cancer treatment is often based on multimodal approaches in locally advanced stages typically including neoadjuvant chemotherapy (NACT). There are limited options for the assessment of prognosis and early identification of future non-responders, which has led to the study of circulating cell-free DNA (cfDNA) and its tumor-derived subset, circulating tumor DNA (ctDNA), for potential use as non-invasive markers for prediction of response and prognosis associated with NACT. Methods: We have evaluated the literature on approaches to the use of cfDNA and/or ctDNA as potential biomarkers for NACT. Results: Out of 142 references going back to 2010, we found there were 87 original research reports, 39 reviews, 10 clinical trial reports and six case reports. A detailed analysis revealed several distinctive ways that markers were evaluated in a clinical setting. The original studies have focused on cfDNA, especially cfDNA integrity, whereby increasing integrity levels correlate with tumor shrinkage, reductions in proliferation markers, and hence indicate a better prognosis. Similarly, epigenetic alterations have shown promising results, with methylated ctDNA levels decreasing in responders. Further studies demonstrated the utility of ctDNA persistence through the NACT as strongly associated with shorter disease-free and overall survival. The most recent approaches of longitudinal ctDNA monitoring were found to be valuable for early identification of patients at high risk for post-operative recurrence. Conclusions: It should be noted that while most reports indicate the important role of circulating DNA in the assessment of prognosis and early detection of recurrence, there is currently only a limited utility in the prediction of eventual neoadjuvant therapy outcomes. Full article

Introduction: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, with a subset progressing to locally advanced (laSCC) or metastatic (mSCC) stages. The introduction of anti-PD1 immunotherapy has transformed treatment, but real-world data remain limited, particularly in immunosuppressed patients. Methods: This single-centre, retrospective study included 189 patients with advanced cSCC treated between 2012 and 2022. Demographic, clinical, and treatment data were analyzed to assess clinical management and outcomes before and after the introduction of anti-PD1. Results: Among the 189 patients, 72.5% were male, with a median age of 79 years. Overall, 86 patients presented with laSCC and 103 with mSCC. In 100 patients, a preceding primary cSCC was documented, and its complete resection (R0) was associated with significantly better overall survival (OS) after diagnosis of advanced disease (p < 0.001). Immunosuppressed patients, including organ transplant recipients and those with chronic lymphocytic leukemia (CLL), had significantly reduced OS (p = 0.017 and p = 0.0059, respectively). First-line treatment prior to 2018 predominantly involved surgery and radiotherapy. Following the introduction of anti-PD1 therapy, its use increased rapidly in both first- and second-line settings. From 2018 onward, the number of advanced cSCC cases discussed at the multidisciplinary tumorboard increased approximately threefold. Median OS was significantly longer for mSCC patients treated in the post-2018 era (p = 0.025), while the survival disadvantage of CLL patients compared to non-CLL patients widened, suggesting limited benefit from advances in systemic therapy in this subgroup. Best overall response to first-line anti-PD1 correlated significantly with OS, with complete responders achieving a 1-year progression-free survival of 83.3%. Conclusions: The introduction of anti-PD1 has demonstrated improved survival outcomes in advanced cSCC, though significant challenges remain for immunosuppressed patients, particularly those with CLL and solid organ transplant recipients. Future research should focus on optimizing treatment for these high-risk groups, therapeutic sequencing, and the role of perioperative (neoadjuvant and adjuvant) immunotherapy strategies. Full article

Background: Spread through air spaces (STAS) is a prognostic factor for survival in non-small cell lung cancer (NSCLC), but the chance to identify it before surgery remains challenging. In this study, we consider clinical, pathological and metabolic factors, with the aim to identify possible STAS predictors in NSCLC. Methods: Clinical and pathological characteristics of patients who underwent anatomical lung resection from 1 January 2018 to 31 December 2023 were retrospectively reviewed and analyzed. Patients with GGO, AIS, or MIA tumors, metastases, or undergoing neoadjuvant therapy were excluded. The parameters assessed by ¹⁸F-FDG PET/CT were: SUVmax, SUVmean, SUVpeak, TLG and MTV. The primary endpoint was the association between clinical, metabolic, and pathologic characteristics with the presence of STAS. A univariate and multivariate logistic regression model was developed to identify independent predictors of STAS. Results: The final analysis was conducted on 224 patients. Non-lepidic-acinar adenocarcinomas showed a statistically significant higher risk of STAS than the lepidic-acinar histotype: 20.8% vs. 4.3%, p = 0.003, OR 5.87, 95%CI 1.83–18.78. Furthermore, tumor grade was significantly associated with STAS: 4.6% in G1–G2 tumors vs. 23.5% in G3 tumors (p = 0.001, OR 5.79, 95%CI 2.12–15.78); as well as lymph vascular invasion (p = 0.034) and tumor size >2 cm (p = 0.017). Multivariate analysis confirmed high tumor grade as an independent risk factor (OR 4.73, 95%CI 1.16–19.23, p = 0.030). Conclusions: In our study, risk of STAS is not correlated with metabolic parameters, while adenocarcinoma subtypes and tumors grading seem to stratify the risk of STAS occurrence. These results may be consolidated in an external validation analysis to possibly better plan the extent of lung resection. Full article

Objective: To examine survival outcomes and identify clinicopathological factors associated with survival in patients with advanced-stage endometrial cancer who received neoadjuvant chemotherapy before interval debulking surgery (NACT-IDS). Methods: A single-center retrospective cohort study was conducted of patients who were diagnosed with advanced-stage (2009 FIGO IIIB, IIIC, IV) endometrial cancer (2012–2024) and underwent NACT-IDS. Tumor response to NACT was determined with computed tomography and the RECIST criteria, and demographic, clinicopathologic, perioperative, and tumor molecular features (mismatch repair protein [MMR] status and p53 pattern) were collected from medical chart review. Association between tumor molecular features and response to NACT was determined. Primary endpoints were progression-free and overall survival, analyzed with univariate Cox and stratified Kaplan–Meier analysis. Results: Of 42 consecutive patients (median age of 68 years), the majority (n = 26; 61.9%) had a partial tumor response to NACT, with only five (11.9%) having a complete response, four (9.5%) having stable disease, and seven (16.7%) having progressive disease. Most cases had no residual tumor after IDS (n = 35; 83.3%). MMR protein status was associated with the tumor response to NACT (p = 0.013), but p53 status was not. During follow-up, 24 patients died (57.1%), and 31 (73.8%) died or had disease progression. Tumor response to NACT and resection margin status were associated with progression-free survival in unadjusted analyses, but no covariate adjustment was possible with limited sample size. Conclusions: This study highlights MMR-deficiency, response to NACT, and surgical resection status as clinicopathologic features of interest for future studies of prognostic factors and alternative therapies in advanced-stage endometrial cancer. Full article

Background/Objectives: Early prediction of pathologic complete response (pCR) during neoadjuvant therapy could improve diagnostic assessment of treatment response, adaptive treatment monitoring, and early prognostic stratification in breast cancer, but longitudinal public MRI archives are not immediately ready for reproducible paired-image modeling. The aim of this study was to develop a reproducible longitudinal breast MRI workflow from the public ACRIN 6698/BMMR2 archive and to compare handcrafted radiomics with frozen deep image embeddings for early treatment-response modeling and imaging-based pCR prediction. Methods: The raw archive was reduced to a validated 183-patient cohort with matched T0 and T1 cropped DCE image–mask pairs, preserved predefined train/test assignment, and binary pCR labels. Handcrafted radiomic features were extracted at T0 and T1 using a MIRP-based workflow, longitudinal delta descriptors were constructed, and train-only cleaning, filtering, and feature selection were applied before predictive modeling. In parallel, lesion-centered paired 2.5D tensors were generated for image-based deep analysis. Exploratory end-to-end paired deep-learning models were evaluated but showed substantial overfitting. Therefore, a frozen pretrained ResNet18 feature-extraction strategy was used to derive T0, T1, DELTA, and AVG image embeddings, which were then modeled using train-only selection and classical classifiers. Results: In the handcrafted radiomics branch, the strongest refined model was the T1-only random forest model with 10 selected features, achieving an AUROC of 0.670 and an AUPRC of 0.405 on the independent test subset. In the frozen deep-embedding branch, the best configuration by AUROC was the DELTA-only random forest model with 30 selected features (AUROC 0.672, AUPRC 0.408), whereas the strongest configuration by AUPRC was the AVG-only logistic regression model with 100 selected features (AUROC 0.666, AUPRC 0.472). End-to-end paired deep-learning models were technically feasible but were not retained because of marked overfitting. Conclusions: A complex public longitudinal breast MRI archive can be converted into a reproducible modeling cohort for early response assessment. Within this framework, handcrafted radiomics and frozen deep image embeddings yielded comparable exploratory discrimination but emphasized different representation spaces: the strongest handcrafted signal was concentrated in the early-treatment T1 phenotype, whereas the strongest deep signal was concentrated in latent longitudinal change and integrated paired-image state. These findings indicate that longitudinal breast MRI-derived biomarkers warrant further investigation for early treatment-response assessment; however, the present models remain exploratory and require independent external validation before any clinical application. Full article

Background: Locally advanced thyroid cancer is associated with a poor prognosis and high surgical morbidity. This study evaluated the feasibility and outcomes of neoadjuvant treatment including targeted therapy with locoregional interventions. Methods: We retrospectively analyzed 17 patients with locally advanced thyroid cancer who received neoadjuvant treatment, including tyrosine kinase inhibitors (TKIs), transarterial embolization (TAE), and radiofrequency ablation (RFA), either alone or in combination. The primary outcome was the proportion of patients who proceeded to R0 or R1 surgical resection following neoadjuvant treatment. Secondary outcomes included tumor response assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and changes in surgical morbidity evaluated using the MGH/MEEI–MSK–MD Anderson surgical morbidity complexity score (MMM score) and the Invasive Thyroid Class. Results: Five patients (29%) achieved R0/R1 resection, including four with R0 resection. Most patients demonstrated reduced tumor burden and surgical complexity, as reflected by improvements in the MMM score and the Invasive Thyroid Class. The objective response rate was 47% and the 12-month progression-free survival rate was 58.2%. Conclusion: Neoadjuvant treatment may improve tumor downstaging and surgical feasibility in selected patients with initially unresectable thyroid cancer. Further prospective studies are required to validate these findings. Full article

Axillary lymph node management in early-stage breast cancer has undergone a fundamental transformation over the past three decades, shifting from routine radical clearance to precision-guided de-escalation. Ultrasound (US) has emerged as the central imaging modality in this paradigm shift, serving as the first-line tool for preoperative nodal assessment, guidance for biopsy and clip placement, monitoring of response to neoadjuvant chemotherapy (NAC), and localization of marked nodes for targeted axillary dissection (TAD). This review systematically examines the evolution of axillary management in early-stage breast cancer through a US-centric lens. We summarize the historical transition from Halstedian axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB), critically appraise the landmark trials—Z0011, AMAROS, OTOASOR, and SOUND—that have progressively de-escalated axillary surgery, and detail the role of US in preoperative staging (including conventional B-mode, superb microvascular imaging, contrast-enhanced US, elastography, and AI-assisted diagnostics), US-guided biopsy and node marking, and post-NAC TAD. We further explore the integration of US with liquid biopsy, multigene profiling, and molecular subtype-guided systemic therapy to enable individualized decision-making. Finally, we propose a stepwise US-centric clinical algorithm and discuss future directions, including AI-powered real-time interpretation, imaging-omics, and US-guided targeted therapy. This review provides a comprehensive framework for incorporating ultrasound as a key component of multidisciplinary decision-making—alongside pathological, surgical, radiotherapeutic, and molecular inputs—in contemporary axillary management. Full article