The presence of bone metastasis represents one of the common and toughest complications of breast cancer that significantly increases the morbidity rate. Currently available therapies for treating breast cancer have been able to ameliorate symptoms, but still suffer from insufficient accumulation of the drugs in bone metastatic sites and severe side effects on the whole body. The use of drug delivery systems based on nanomedicine has been demonstrated to be a promising approach in improving drug accumulation and pharmacodynamics of drugs in pre-clinical models. Engineered nanoparticles could be tailored in order to improve accumulation in the tumor environment and provide the delivery of drugs to bone metastatic regions. Moreover, recent advances in nanotechnology have provided many new options for imaging and therapeutic experiments in metastatic cancers. Modulation of tumor‑associated macrophage (TAM) polarization represents one of the recently described strategies since M2-like phenotype contributes to tumor growth, immunosuppression and metastasis development, while induction of M1-like phenotype has been proven to be effective in enhancing anti-tumor immune response in pre-clinical models. In this review, we discuss recent advances in the nanomedicine approach that targets TAM polarization in breast cancer bone metastasis, the rationale of the proposed strategies, therapeutic potential and limitations.
Background:Breast cancer remains a leading cause of female mortality worldwide, with therapeutic benefit limited by tumor heterogeneity and drug resistance. Identification of novel therapeutic targets through integration of genetic causality inference and functional validation is urgently needed. Methods:Plasma protein quantitative trait loci (pQTL) from the Fenland cohort (~10,700 individuals) and the FinnGen R10 SomaScan subset (n = 828) were integrated with breast cancer genome-wide association study data from the Breast Cancer Association Consortium (122,977 cases and 105,974 controls). Causal protein-disease relationships were inferred using summary-data-based Mendelian randomization (SMR), with colocalization and HEIDI tests. Multi-level validation was performed using TCGA-BRCA transcriptomic data. Functional validation included CCK-8, EdU, wound healing, Transwell invasion, and flow cytometry apoptosis analysis evaluated CPNE1 knocdown and/or overexpression of the MST1 gene which encodes macrophage-simulating protein (MSP). Results:SMR identified 23 proteins in Fenland and 10 in FinnGen at FDR < 0.05. MST1/MSP and CPNE1 were supported in both datasets with PP.H4 ≥ 0.80 and non-significant HEIDI tests. Genetically predicted circulating MSP was positively associated with breast cancer risk, whereas circulating CPNE1 showed an inverse association. TCGA-BRCA showed higher CPNE1 mRNA in tumors (P = 2.57×10⁻25) and lower MST1 mRNA (P = 3.04×10⁻23). CPNE1 expression was highest in triple-negative breast cancer and correlated positively with clinical stage (ρ = 0.211), whereas MST1 expression was lowest in triple-negative breast cancer and correlated inversely with stage (ρ = -0.164). In T47D and MDA-MB-231 cells, CPNE1 knockdown and MST1 overexpression each reduced proliferation, migration, and invasion and increased apoptosis; the combined group showed greater changes than either single intervention. Conclusion:This study prioritizes the MST1 gene, which encodes MSP, and CPNE1 as candidate proteins for further investigation in breast cancer. However, the circulating-protein associations, tumor-mRNA patterns, and cell-autonomous perturbations represent distinct and directionally discordant biological contexts. The findings therefore support context-dependent candidate roles and justify mechanistic, in vivo, and formal interaction studies, but do not yet establish therapeutic efficacy or synergy.
Bilateral primary breast cancer (BPBC) accounts for 2-12% of all breast cancers, with an increasing incidence trend. However, its clinical management remains challenged by the absence of unified diagnostic criteria, lack of evidence-based therapeutic guidelines, incomplete prognostic assessment frameworks, and a paucity of data from Asian populations. This narrative review critically synthesizes literature from PubMed, Web of Science, and CNKI databases (2020-2025) across seven dimensions: diagnosis and differential diagnosis, clinicopathological features, risk factors, imaging, genetics, treatment, and prognosis. Current evidence demonstrates that SBBC and MBBC exhibit significant heterogeneity in age at onset, molecular subtype distribution, and prognosis, with bilateral receptor discordance rates of 11-23%, mandating separate evaluation of each side; all current treatment recommendations are extrapolated from unilateral breast cancer evidence, leaving decisions in cases of subtype discordance without evidence-based support; and existing genetic risk models and clinical evidence are predominantly derived from Western populations, with only limited single-center retrospective data available from Asian populations but systematic, high-quality evidence remaining insufficient, such that direct application carries a risk of systematic bias. This review aims to provide an evidence-based reference for standardized clinical practice, emphasizing the urgent need to establish unified diagnostic criteria, develop population-specific risk models for Asian populations, and conduct dedicated prospective trials.
Background:Reliable biomarkers for predicting response to neoadjuvant chemotherapy (NAC) in breast cancer remain limited. This study evaluated the association of pretreatment Albumin-to-Neutrophil Ratio (ANR) and IronMLR with pathological response following NAC. Methods:This retrospective study included 71 patients with breast cancer treated with NAC. Pretreatment inflammatory indices were calculated from routine blood samples obtained before treatment initiation. ANR and IronMLR were compared across pathological response groups. Receiver operating characteristic (ROC) analysis was performed to evaluate predictive performance. Results:The mean age was 53.9±10.6 years, and pathological complete response (pCR) was achieved in 30 patients (42.3%). ANR was not significantly associated with pathological response (p=0.121). In contrast, IronMLR levels differed significantly among complete responders, partial responders, and non-responders (p<0.001). ROC analysis demonstrated favorable discriminatory performance of IronMLR for predicting treatment response, with an area under the curve of 0.909 (95% CI, 0.832-0.986; p<0.001). An IronMLR cut-off value of 175.40 yielded 77.4% sensitivity and 77.8% specificity. Patients with IronMLR ≥175.40 exhibited significantly higher response rates than those with lower values (96.0% vs 66.7%, p=0.001). Conclusion:Pretreatment IronMLR was significantly associated with pathological response following NAC in patients with breast cancer, whereas ANR showed no significant association. Given its simplicity and accessibility, IronMLR may represent a potentially useful biomarker for treatment stratification. Further prospective multicenter studies are warranted to validate these findings.
Introduction:The SWI/SNF (SWItch/Sucrose Non - Fermentable) complex is a multi - subunit, ATPase - dependent chromatin - remodeling complex involved in regulating key cellular processes. Tumors with SWI/SNF loss tend to be poorly differentiated and aggressive. Triple - negative breast cancer (TNBC) typically has a high histological grade and a poor prognosis. Given the limited reports on the SWI/SNF complex in breast cancer, we focused on its role in TNBC. Methods:Using tissue microarray and immunohistochemistry (IHC), we evaluated the expression of four important subunits of the SWI/SNF complex (SMARCB1, SMARCA2, ARID1A, and SMARCA4) in 104 TNBC tissues, which included 96 cases of conventional TNBC and 8 cases of low - grade TNBC. Additionally, we evaluated the endogenous expression of the four subunits in five breast cancer cell lines by real - time quantitative PCR (RT - qPCR). These cell lines consisted of two TNBC cell lines (MDA - MB - 231, MDA - MB - 468) and three non - TNBC cell lines (MCF - 7, T47D, and MDA - MB - 453). Results:The IHC results indicated that the deletion rate of SMARCA2 was the highest in TNBC compared with other subunits (91/104, 87.5%) (p < 0.0001), and SMARCA4 had the highest retention rate (98/104, 94.2%). Whether low - grade TNBC was excluded or not, there was no significant difference between the deletion rate and various clinicopathological parameters. Consistently, we found that SMARCA2 exhibited the lowest expression level across all five cell lines (p < 0.01). SMARCA4 showed the highest expression in all cell lines except MDA - MB - 453, in which ARID1A expression was the highest. Conclusion:These results indicate that TNBC is characterized by a high proportion of SMARCA2 deletion and positive expression of SMARCA4, which are significant molecular features. The roles and potential mechanisms of these two factors in TNBC require further investigation.
