Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become a cornerstone in the first-line management of hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer. Despite their clinical efficacy, most patients eventually experience disease progression, and optimal treatment strategies following CDK4/6 inhibitor resistance remain unclear. Emerging evidence suggests that switching endocrine therapy (ET) while continuing cyclin inhibition may provide additional clinical benefit. Dalpiciclib, a selective CDK4/6 inhibitor, in combination with physician-selected ET, represents a potential option in this setting. Concurrently, 16α-[18F]fluoro-17β-estradiol ([18F]FES) PET/CT, a novel imaging modality targeting estrogen receptors (ER), enables non-invasive, whole-body assessment of ER expression in metastatic lesions, offering a personalized approach to treatment selection. This is a prospective, single-center, single-arm Phase II clinical trial evaluating the efficacy and safety of dalpiciclib plus ET in HR+/HER2- advanced breast cancer patients who progressed on prior CDK4/6 inhibitor therapy. Forty eligible patients with confirmed metastases and at least one [18F]FES-positive lesion will be enrolled. Participants will receive dalpiciclib combined with ET as determined by the treating physician. The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Beyond evaluating efficacy, this single-center phase II trial will provide practical insight into the feasibility of [18F]FES PET/CT-guided patient selection, including standardized imaging workflows and multidisciplinary implementation in routine clinical research. Positive outcomes may support a personalized, imaging-guided strategy to prolong disease control after prior CDK4/6 inhibitor progression. Approved by the Ethics Committee of Peking Union Medical College Hospital (Approval number: K3629); registered at ClinicalTrials. gov (NCT05613270).

Preoperative Prediction of Axillary Lymph Node Metastasis in Breast Cancer Using a Three-tier MRI Radiomics Model with Nested Cross-validation.

Whole genome sequencing of locally advanced and metastatic breast carcinoma unravels relevant molecular signatures and novel events.

Metastatic presentation of breast cancer in India: evidence from national cancer registry (2009-2020).

Real-world progression-free survival 2 (PFS2) and tumor response of CDK4/6 inhibitors plus an aromatase inhibitor in patients with HR+/HER2- metastatic breast cancer in US routine clinical practice.

Hormone receptor-positive, human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC) represents the most common subtype of MBC and has undergone substantial therapeutic evolution. Treatment has shifted from sequential endocrine therapy (ET) and chemotherapy toward personalized strategies incorporating molecularly targeted agents and antibody-drug conjugates (ADCs), with increasing emphasis on quality of life and shared decision making. CDK4/6 inhibitors plus ET remain a first-line standard of care in high-resource settings, demonstrating consistently improved progression-free survival (PFS) and, for select agents, overall survival (OS). Management in special populations requires additional consideration of trial and real-world data, toxicity profiles, and patient preferences. Beyond ET, ADCs are reshaping the landscape. Trastuzumab deruxtecan expanded therapeutic utility across HER2-low and HER2-ultralow disease, whereas sacituzumab govitecan and datopotamab deruxtecan provide later-line options. As ADCs emerge as earlier therapies, questions regarding sequencing, cross-resistance, and toxicity remain central to clinical decision making. Metastasis-directed therapy (MDT) in oligometastatic and oligoprogressive breast cancer also requires nuanced decision making. Despite high local control rates with stereotactic body radiotherapy, randomized trials have not demonstrated consistent improvements in PFS or OS in unselected populations. Current evidence supports systemic therapy as the foundation of management, with MDT selectively considered for oligoprogression, symptom prevention, or within clinical trials. Ultimately, management of hormone receptor-positive/HER2-negative MBC requires dynamic integration of tumor biology, systemic therapy advances, and patient-defined goals of care. As therapeutic complexity increases, shared decision making and equitable access to evidence-based and supportive care services remain essential for delivering high-quality, individualized oncology care.

Unmet need for patients with metastatic triple-negative breast cancer initiating first-line treatment: data from the prospective German tumor registry OPAL.

Antibody-drug conjugate sequencing in HER2-positive metastatic breast cancer: Real-world outcomes of trastuzumab deruxtecan with and without prior T-DM1 exposure.

CDK4/6 inhibitor ribociclib and doxorubicin combination treatment inhibits breast cancer bone metastasis and enhances T-cell targeted therapy.

International comparisons of survival after recurrent metastatic breast cancer in four countries: A population-based study.

Breast cancer (BC) remains one of the leading causes of cancer-related mortality among women worldwide, with distant metastasis being the primary contributor to poor prognosis. However, the molecular mechanisms driving BC metastasis are not yet fully understood. We integrated three public microarray datasets (GSE14776, GSE103357, and GSE32489) to identify the differentially expressed genes (DEGs) associated with breast cancer metastasis. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene identification were performed using bioinformatics tools including DAVID, STRING, Cytoscape, and R. The prognostic significance of hub genes was assessed using Kaplan-Meier plotter and GEPIA. Expression validation was conducted through UALCAN, immunohistochemistry (IHC), and single-cell RNA sequencing (scRNA-seq) analysis from the GSE180286 dataset. A total of 295 co-DEGs were identified across the three datasets, enriched in pathways such as MAPK signaling, Rap1 signaling, and cell adhesion molecules. Twenty hub genes were identified from the PPI network, with eight showing strong prognostic value. Among them, PRC1 and POLR3H emerged as potential novel biomarkers. IHC confirmed the differential protein expression of PRC1, CDCA8, KIF14, and POLR3H. scRNA-seq analysis revealed that these hub genes were predominantly expressed in malignant epithelial and EMT (epithelial-mesenchymal transition) cells, particularly those from metastatic lymph node sites. This integrative analysis combining bulk and single-cell transcriptomic data identified key metastasis-associated genes in breast cancer. PRC1 and POLR3H, in particular, may serve as novel prognostic biomarkers and potential therapeutic targets.

Triple-negative breast cancer (TNBC) remains a highly aggressive disease with limited therapeutic options, and metastasis is the leading cause of patient mortality which highlights a major unmet medical need. Nevertheless, the mechanisms regulating metastatic progression remain poorly understood. Extracellular vesicles (EVs) have recently emerged as key mediators of the intercellular communication. Ubiquitously secreted, these nanoparticles provide a convenient and informative glimpse into cellular physiology given that their molecular composition shall reflect the state of their parent cell. Therefore, in this study, we aim to show that lipid profiles of EVs may differentiate malignant from non-malignant cells and to reveal biomarkers associated with TNBC. For this reason, we investigated the lipid composition of EVs released by cancer cells (MDA-MB-231, MDA-MB-453 and MDA-MB-468 representing TNBC) and non-malignant (MCF10A) human breast epithelial cells, with the goal of highlighting specific lipid profiles that might serve as potential biomarkers for TNBC. EV isolation and characterization were performed in accordance with MISEV2023 guidelines, while lipidomic profiling was carried out using an untargeted liquid chromatography and high-resolution mass spectrometry approach. We annotated over 500 complex lipid species. Multivariate analysis was used to explore major trends in the dataset, separating EVs derived from cancerous and non-cancerous cells and capturing differences among TNBC-derived EVs, reflecting their distinct genetic background. Further supervised modelling revealed distinct TNBC lipidomic signatures including phosphatidylcholines with alkyl chains of C18:0_C19:1, C20:1_C22:5, C18:1_C22:6 or C15:0_C22:5, C17:0_C20:3 and phosphatidylserine C32:0 which consistently emerged as shared lipid species across TNBC-derived EVs, highlighting their potential as biomarkers for the detection of TNBC. Furthermore, we highlighted lipid subsets specific to each of the investigated TNBC's source of EVs for in-depth molecular subtyping of TNBC.

Pseudoginsenoside F11 enhances YBX1-mediated transcriptional repression of PRPS2 to inhibit the stemness and pulmonary metastasis of triple- negative breast cancer.

Chemotherapy (CT) remains the standard first-line treatment for advanced triple-negative breast cancer (aTNBC), despite the emergence of innovative therapies, including targeted therapies (TT) and immune checkpoint inhibitors (ICI). Studies have shown that the treatment strategies for aTNBC vary widely, with inconsistent efficacy acrossdifferent treatment modalities. A comprehensive search was carried out in electronic databases, such as PubMed and Embase, for systematic reviews and randomized clinical trials (RCTs) that investigated the efficacy of TT, ICI, and CT to treat aTNBC until June 2025. Seventeen published meta-analyses and 52 RCTs reporting the prognosis of the disease treated with TT, ICI, and CT in aTNBC patients were analyzed. It showed that in terms of prolonging PFS, both the TT group and the ICI group were superior to the CT group [ICI: HR = 0.81 (0.69, 0.94); TT: HR = 0.68 (0.62, 0.74)]. In terms of OS, the TT group was superior to the CT group [HR = 0.77 (0.68, 0.88)]. In the subgroup analysis of TT, compared with CT alone, both sacituzumab govitecan (SG) monotherapy and trilaciclib combined with chemotherapy (TRI_CT) significantly improved the time of PFS [SG: HR = 0.41 (0.30, 0.56); TRI_CT: HR = 0.62 (0.46, 0.86)] and OS [SG: HR = 0.48 (0.33, 0.70); TRI_CT: HR = 0.41 (0.28, 0.59)]. This umbrella review supports SG monotherapy and TRI_CT as the first choice for patients with aTNBC. Additionally, the review was rated as high-quality evidence using AMSTAR 2, the credibility classification standard, and GRADE rating. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and is registered with PROSPERO: CRD420251034666.

Bone metastasis (BoM) is a frequent complication of solid tumors, leading to poor prognosis and reduced survival. CD103⁺ tumor-infiltrating lymphocytes (TILs) are critical for antitumor immunity, yet studies have largely focused on CD8⁺ subsets, leaving CD103⁺CD4⁺ cells poorly characterized. Bone aspirates containing malignant cells were obtained from patients with symptomatic spinal and/or pelvic metastases of breast cancer (BC), prostate cancer (PC), or non-small cell lung cancer (NSCLC). Age-matched bone marrow samples from individuals without malignancy (NMCs) were controls. Multiparametric flow cytometry (MFC) was utilized to assess the expression of CD103 and exhaustion markers (TIGIT, PVRIG, KIR2DL5, CD39) in CD3+ cells. CD103⁺CD3+ T cells are significantly elevated in BoM compared to NMC, driven by an increase in CD103⁺CD4⁺ cells, despite a relative decrease in frequency of CD103⁺CD8⁺ cells. Furthermore, CD103+CD4+ cells from BoM displayed a significantly increased fraction of the central memory (CM) phenotype. Expression and coexpression of TIGIT, PVRIG, KIR2DL5 and CD39 on CD103+ cells both in the CD4 and CD8 compartment was significantly increased in BoM, compared within CD103- within BoM and CD103+ in NMC. In conclusion, BoM exhibit a distinct T-cell composition, highlighted by an increase in CD103⁺CD4⁺ cells displaying an increased CM phenotype. In BoM, cregulatory receptor expression is increased on CD103⁺ T cells, with distinct coexpression signatures in both CD4⁺ and CD8⁺ cells. Functional studies will determine whether targeting these checkpoint pathways can improve immunotherapy for metastatic bone disease.

FAP-targeting peptide-directed nanoprobes enable tumor microenvironment-activatable MR/NIRF imaging of breast cancer primary tumor and lung metastases.

Association between diarrhea and survival in patients with HER2-positive advanced breast cancer treated with pyrotinib-based therapy: A landmark analysis from the real-world PRETTY study.

Economic benefit of expanding mammography screening for breast cancer in Colombia: A cost modelling analysis.

Objective: To construct a prediction model integrating molecular markers, imaging features, and clinicopathological characteristics for brain metastasis (BM) of breast cancer and provide a quantitative tool for clinical precise stratification of breast cancer. Methods: A total of 346 breast cancer patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from January 2018 to December 2023 were enrolled, including 214 cases in the BM group and 132 cases in the control group. The patients were divided into a training set (242 cases) and an internal validation set (104 cases) at a ratio of 7∶3. A total of 1,483 female breast cancer patients from the Surveillance, Epidemiology, and End Results Program (SEER) database (2017-2021) were used as the external validation set, including 530 cases in the BM group and 953 cases in the control group. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to screen key features, and a nomogram prediction model for breast cancer BM was constructed based on the results of multivariate logistic regression analysis of factors influencing breast cancer BM. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the model performance, and internal and external validations of the model were conducted. Results: LASSO regression based on the training set screened out 11 key features, namely, primary side, primary quadrant, number of lesions, histological grade, differentiation degree, Ki-67 index, N stage, clinical stage, lymphovascular invasion, aspect ratio, and lesion margin morphology. Multivariate logistic regression analysis showed that the number of lesions (multiple lesions: OR=7.49, 95% CI: 3.59-15.64), histological grade (grade 2: OR=9.02, 95% CI: 4.87-16.70; grade 3: OR=12.57, 95% CI: 6.60-23.94), differentiation degree (moderate differentiation: OR=0.18, 95% CI: 0.06-0.53; well differentiation: OR=0.02, 95% CI: 0.01-0.06), Ki-67 index (15%-29%: OR=0.28, 95% CI: 0.11-0.74; ≥30%: OR=4.01, 95% CI: 2.45-6.58), clinical stage (stageⅢ: OR=3.53, 95% CI: 1.76-7.07; stage Ⅳ: OR=35.43, 95% CI: 13.97-89.91), and lymphovascular invasion (presence of lymphovascular invasion: OR=12.42, 95% CI: 6.84-22.53) were independent influencing factors for breast cancer BM. The nomogram prediction model for breast cancer BM constructed based on the results of multivariate logistic regression analysis had areas under the curve (AUCs) for predicting breast cancer BM of 0.869 (95% CI: 0.826-0.912), 0.857 (95% CI: 0.817-0.897), and 0.868 (95% CI: 0.849-0.887) in the training set, internal validation set, and external validation set, respectively. All calibration curves were close to the reference line, and when the threshold probability was >0.2, the net benefit was significantly higher than that of the "treat all" or "treat none" strategy. Conclusions: A nomogram prediction model for breast cancer BM integrating multi-dimensional information (molecular subtypes, imaging features, and clinicopathological characteristics) was successfully constructed. This model has good ability to distinguish breast cancer patients with BM from thosewithout, with favorable calibration and clinical applicability, and provides a quantitative tool for clinical assessment of the risk of breast cancer BM.

CDK4/6 inhibitors combined with endocrine therapy constitute the global first-line standard of care for HR + /HER2 - advanced breast cancer (ABC), yet no head-to-head trials comparing different CDK4/6 inhibitors have been conducted, and real-world comparative data in Chinese patients is currently unavailable. We conducted a multicenter retrospective study of 341 Chinese patients with HR + /HER2 - ABC who received first-line palbociclib (n = 177), abemaciclib (n = 114), or dalpiciclib (n = 50) from 2018 to 2023. The primary endpoint was progression-free survival (PFS); secondary endpoints included safety, tolerability, and objective response rate. Median PFS was 24months for palbociclib and 32months for abemaciclib, while median PFS for dalpiciclib was not reached. Abemaciclib significantly prolonged PFS compared with palbociclib (palbociclib vs. abemaciclib: adjusted HR = 1.86, 95% CI 1.24-2.79), with consistent benefits in premenopausal, postoperative recurrence, progesterone receptor-positive, HER2-low, luminal B, visceral metastasis, and endocrine-resistant subgroups (all p < 0.05). Overall tolerability was comparable, though palbociclib and dalpiciclib were associated with higher myelosuppression, whereas abemaciclib more frequently caused low-grade diarrhea. This is the larger real-world study to compare different CDK4/6 inhibitors in Chinese HR + /HER2 - ABC patients. Abemaciclib demonstrated a significant PFS advantage over palbociclib while maintaining a manageable safety profile, particularly benefiting biologically aggressive or treatment-resistant subgroups. These findings provide population-specific evidence to guide individualized CDK4/6 inhibitor selection and refine first-line treatment strategies for Chinese patients with HR + /HER2 - ABC.