Breast Cancer : Targets and Therapy最新文献

Background: Limited real-world data are available on the effectiveness and safety of trastuzumab deruxtecan (T-DXd, DS8201a) in patients with HER2-positive and HER2-low metastatic breast cancer (MBC), particularly within the Chinese population.

Methods: Between 2022 and 2025, 98 patients with MBC treated with T-DXd were retrospectively enrolled at Fudan University Shanghai Cancer Center. Patients were categorized as HER2-positive and HER2-low cohort. Clinical outcomes including objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and clinical benefit rate (CBR), were assessed and compared between cohorts. The primary endpoint of the study was PFS, which was estimated using the Kaplan-Meier method and compared using the Log rank test.

Results: Among the 98 patients, the median PFS was 15.0 months. The ORR, DCR, and CBR were 48.0%, 69.4%, and 41.8%, respectively. HER2-positive patients experienced longer PFS compared to HER2-low patients (not reached vs 9.0 months). Among HER2-low patients, liver metastases were associated with poorer outcomes. Patients with brain metastases achieved a median PFS of 15.5 months and a 1-year PFS rate of 65.3%. Grade ≥3 adverse events included neutropenia (20.4%), nausea (5.1%), anemia (4.1%), and interstitial lung disease in 6.1% of patients, leading to discontinuation in 2.0%.

Conclusion: In this real-world analysis, T-DXd demonstrated robust clinical activity in both HER2-positive and HER2-low MBC, consistent with the findings from the DESTINY-Breast clinical trials. Notably, we identified several clinically relevant prognostic factors, including HER2 status, metastatic site, treatment line, and prior therapies. These findings support the broader clinical application of T-DXd and offer insights into individualized treatment selection.

Despite substantial progress in the diagnosis and treatment of breast cancer, current therapeutic regimens exhibit limitations, necessitating the identification of more robust biomarkers to optimize personalized strategies. Circulating tumor DNA (ctDNA), as a non-invasive liquid biopsy modality, overcomes the inherent constraints of biopsies in capturing tumor heterogeneity. Accumulating evidence from prospective cohort studies demonstrates the clinical utility of ctDNA in risk stratification, guidance of therapeutic decision-making, recurrence surveillance and other clinical applications. Furthermore, ctDNA profiling enhances real-time pharmacodynamic monitoring and accelerates drug development by identifying molecular responders. The methodical requirements and challenges inherent in implementing liquid biopsy assessments in the clinic are examined. These encompass critical pre-analytical variables, the need for highly sensitive and specific analytical techniques, standardization of assays and bioinformatics pipelines across laboratories and the complexities of interpreting results. This review synthesizes current evidence supporting ctDNA integration into breast cancer management frameworks and systematically addresses its methodological challenges and clinical limitations.

Background: Bone metastasis affects nearly 70% of patients with advanced breast cancer, significantly influencing patient survival. Osteoclasts play a crucial role in osteolysis and the proliferation of bone tumor cell metastasis. Although previous studies have established Anxa2 as a critical factor in the invasion and metastasis of breast cancer, its involvement in bone metastasis remains poorly understood.

Methods: The correlation between ANXA2 expression and survival was analyzed in breast cancer cohorts. Enrichment analysis was performed to explore ANXA2-associated signaling pathways. RAW264.7 cells were induced to differentiate into osteoclasts using conditioned media from breast cancer cells, and osteoclastogenesis was quantified using the TRAP assay. Breast cancer cell lines with either Anxa2 overexpression or knockdown were established to assess the impact on osteoclastogenesis. The mRNA and protein expression levels were analyzed by RT-PCR and Western blot. The role of STAT3 in regulating RANKL expression was evaluated using a dual luciferase reporter assay.

Results: ANXA2 was significantly upregulated in breast cancer patients and associated with poor survival. GO and KEGG analyses revealed that ANXA2 substantially modulated signaling pathways involved in bone metastasis. Furthermore, ANXA2 notably enhanced the differentiation of RAW264.7 cells into osteoclasts and upregulated genes associated with osteoclast differentiation. Additional investigation showed that ANXA2 markedly activated the STAT3 signaling pathway and increased RANKL expression. The dual luciferase reporter assay demonstrated that STAT3 directly bound to the -1804 region of the RANKL promoter, thereby regulating RANKL expression.

Conclusion: This study identifies ANXA2 as a key regulator of osteoclast differentiation through STAT3-mediated upregulation of RANKL, driving bone metastasis in breast cancer. These results highlight the potential of targeting the ANXA2/STAT3/RANKL axis as a therapeutic strategy to combat bone metastasis.

Objective: To explore the effects of Clinacanthus nutans extract (CnE) on triple-negative breast cancer (TNBC) and mechanism of action.

Methods: In vitro, the human TNBC cell lines were treated with the extract at various concentrations. Cell viability was assessed using the CCK8 assay. In vivo, establishing a subcutaneous xenograft tumor model of TNBC, Hematoxylin-eosin staining and TUNEL assay were used to evaluate the effect of CnE on tumor proliferation. Tumor proteins were extracted, Quantitative proteomics and subsequently analyzed using bioinformatics approaches. Finally, immunohistochemistry evaluates the protein expression differences of ATP2A3, PLA2G4A, and ITPK1.

Results: In vitro, CnE inhibited TNBC cell proliferation in a concentration-dependent manner, with IC50 values of 420 ± 35 μg/mL (MDA-MB-231) and 380 ± 28 μg/mL (MDA-MB-468), showing maximal 68.5% inhibition at 800 μg/mL (p < 0.001). The TNBC xenograft model was successfully established, and tumours in the extract-treated group were markedly smaller than those in the saline group. On day 28, the tumour inhibition rate was 28.66%, significantly higher than that in the saline group (P < 0.05). Haematoxylin-eosin staining staining and TUNEL assay showed increased tumor necrosis and apoptosis induction.(P < 0.001). Proteomic analysis showed that among the 4,908 identified proteins, 80 were upregulated, and 7 were downregulated. Bioinformatics analysis indicated involvement in the extracellular matrix, fatty acid metabolism, cell apoptosis, ferroptosis, immune response, choline metabolism, and amino acid metabolism. Immunohistochemistry revealed increased expression of ATP2A3 (1.3-fold, p < 0.05), PLA2G4A (1.6-fold, p < 0.05) and ITPK1 (3.2-fold, p < 0.01) proteins in the extract group compared to the control group.

Conclusion: CnE inhibits TNBC cell proliferation, suppresses tumor growth, The mechanism likely involves multiple biological processes and pathways, Key pathways included apoptosis, ferroptosis, and necroptosis signaling.

Breast cancer is a leading cause of mortality in women worldwide, primarily due to challenges in early detection and limited access to timely treatment. While mammography is widely used, it may produce false positives and lead to overdiagnosis. Recent advancements suggest that electronic nose technology, based on the detection of volatile organic compounds (VOCs), may offer a complementary non-invasive approach to breast cancer screening. This systematic review evaluates current detection methods and explores the feasibility and diagnostic value of the electronic nose, assessing its integration into existing clinical strategies.

Methods:

Study design: A systematic review was conducted following PRISMA guidelines.

Eligibility criteria: Seventy-six original articles were included, alongside data from eight additional studies. Eligible studies were published in English or Spanish, evaluated VOCs as a breast cancer screening method, and reported identified VOCs. Systematic reviews, duplicates, editorials, and articles without full-text access were excluded. Information sources and search strategy: Searches were conducted in PubMed, Web of Science, Wiley Online Library, and Science Direct between September and October 2024. Keywords included: volatile organic compounds, breath biomarkers, volatolomics, breast cancer, breast carcinoma, screening, detection, and electronic nose. A total of 581 articles were retrieved: 64 from PubMed, 44 from Web of Science, 152 from Wiley, and 321 from Science Direct.

Study selection: Zotero was used for reference management and duplicate removal. Two reviewers independently screened titles and abstracts; eligible full texts were reviewed, and discrepancies resolved by consensus.

Data extraction: A standardized form was used to collect author, publication year, population, intervention, comparator, main results, and analysis-relevant data. Three reviewers performed the extraction independently.

Purpose: Thrombocytopenia is a common adverse event associated with trastuzumab emtansine (T-DM1) treatment in patients with HER2-positive metastatic breast cancer. This study aims to evaluate the incidence, clinical characteristics, and risk factors of T-DM1-associated thrombocytopenia.

Patients and methods: This retrospective study included patients with breast cancer who received T-DM1. Thrombocytopenia was defined as a platelet count of less than 100 × 10⁹/L. Potential risk factors for thrombocytopenia were analyzed.

Results: The study cohort consisted of 47 patients with a median age of 55 years, including one male patient. Thrombocytopenia was observed in 74.5% of patients during T-DM1 treatment. A total of 63.3% of patients with Ki-67 expression levels ≥30% experienced thrombocytopenia, which was significantly lower than the 94.1% incidence in patients with Ki-67 expression <30% (P=0.034). Patients with completed or ongoing T-DM1 treatment had a thrombocytopenia incidence of 90.5%, compared to 64% in those who discontinued treatment (P=0.036). Although not reaching statistical significance, concurrent radiotherapy was associated with a higher incidence of thrombocytopenia (87.5%). After appropriate interventions, 70% of patients showed restored platelets, while 17.1% required dose reductions.

Conclusion: Thrombocytopenia is a prevalent adverse event during T-DM1 treatment in real-world practice. An increased incidence with concurrent radiotherapy was observed. While the incidence of thrombocytopenia appears to rise with prolonged exposure in completed or ongoing T-DM1, it may have a minor impact on the overall duration of therapy. Future studies should examine these findings to guide prophylactic strategies and interventions for high-risk patients.

Modern Western medicine uses surgeries, chemotherapy, targeted therapy, and radiotherapy to inhibit breast cancer cells through pathways such as apoptosis, necrosis, and autophagy. However, for triple-negative breast cancer (TNBC), a highly aggressive subtype lacking targeted therapies, conventional chemotherapy often leads to severe side effects and drug resistance, thereby limiting its clinical efficacy. Immunogenic cell death (ICD) can prompt dying tumor cells to release antigens and activate anti-tumor immune responses, converting "cold tumors" into "hot tumors". This opens up a new direction for overcoming tumor drug resistance and enhancing the efficacy of traditional therapies. Additionally, Xihuang Pill (XHP) has the potential for immunomodulation and chemotherapy sensitization. Studies have found that as an ICD inducer, XHP can trigger the production of three key damage-associated molecular patterns (DAMPs): HSP membrane translocation, massive ATP release, and HMGB1 secretion. The main active components of XHP include bilirubin, volatile oil, pentacyclic triterpenoids (such as boswellic acid), and steroids (such as hyodeoxycholic acid). These components possess anti-tumor effects, as well as functions in immunomodulation, efficacy enhancement, and toxicity reduction. This article elaborates on the role and mechanism of XHP in treating TNBC from aspects such as formula analysis, the mechanism of immunogenic cell death, the anti-tumor immune effects of XHP, and its relationship with immunogenic cell death. The aim is to provide a theoretical basis for the clinical application of XHP in treating TNBC through the immunogenic cell death pathway and to promote the secondary development of this medicine.

Introduction: The Bystin gene (BYSL) contributes to cancer development and is a probable therapeutic target in cancer therapy. However, no systematic studies have been conducted on BYSL value in pan-cancer diagnosis, prognosis, and immunology.

Methods: We performed a pan-cancer analysis of BYSL using TCGA, GEO, and other databases to assess its expression, clinical significance, genetic variants, methylation, and immune correlation. Enrichment analysis was applied to predict BYSL-related pathways. We analyzed BYSL protein levels in corresponding breast cancer (BRCA) tissue samples to validate our findings using Western blot assays. A tissue microarray was deployed to verify BYSL expression in BRCA tissues by immunohistochemical staining. Moreover, we comprehensively analyzed the function of BYSL in BRCA initiation and development through CCK-8, transwell invasion, migration assays, and cell scratch assays for migration ability assessment.

Results: Through the study, BYSL was significantly overexpressed in the majority of cancers relative to normal tissues, with different expression patterns at different clinicopathological stages. In most cancer types, BYSL exhibits moderate to high diagnostic value, and overexpressed BYSL represents an independent prognosis factor in patients having BRCA, HNSC, KICH, LIHC, OV, and SARC cancers. Mutations in BYSL are distributed in most cancers and are related to prognosis. Most tumors have elevated levels of m6A methylation compared to normal tissues, while their promoter regions exhibit low levels of methylation. Additionally, BYSL expression displayed a positive correlation with MDSC immune infiltration. Further enrichment analysis showed the involvement of BYSL in important biological processes (BP), In addition, BYSL was overexpressed in BRCA tissues and promoted their proliferation, invasion, and migration compared to matched normal breast tissues.

Discussion: Our study showed that BYSL is an important biological indicator for predicting pan-cancer survival outcomes and immune characteristics and elucidated BYSL expression and role in BRCA, which highlights its therapeutic potential in BRCA.