Breast Cancer : Targets and Therapy最新文献

Purpose: Through network pharmacological prediction and in vitro experimental verification, the mechanism of action of Lianqiao Jinbei Decoction (LJD) in inhibiting HER2-positive breast cancer cells was clarified, providing experimental evidence for its treatment of HER2-positive breast cancer.

Methods: Network pharmacology method was used to construct the potential target network of LJD in the treatment of HER2+ breast cancer. After cell culture in vitro, the proliferation of HER2+ SK-BR3 breast cancer cells was investigated using CCK-8 technique. The apoptotic potential of SK-BR3 cells was detected by flow cytometry, and the migration of SK-BR3 cells was detected by cell scratch assay. The expression of HER2 protein in SK-BR3 breast cancer cells was detected by ELISA.

Results: HER2 was identified as the central gene and quercetin, β-sitosterol, and luteolin were the primary active ingredients using network pharmacology analysis. Serum-containing LJD medication can stop SK-BR3 cells from proliferating (P<0.05). Serum-containing LJD drugs at high, medium, and low concentrations may induce SK-BR3 cell death (P<0.05). LJD serum at high, medium, and low concentrations reduced the migration of SK-BR3 cells (P<0.05). The expression of HER2 protein was decreased by LJD high, medium, and low concentration drug-containing serum (P<0.05).

Conclusion: Regarding treating HER2-positive breast cancer, LJD has a multi-component, multi-target, and multi-pathway mode of action. The primary target of LJD's activity is the HER2 protein. Serum-containing LJD medication can prevent SK-BR3 cells from proliferating and migrating while encouraging their apoptosis. This effect may be attained by preventing HER2 protein expression.

Objective: This study aims to evaluate the simultaneous implant and dermal flap technique for breast reconstruction following skin-sparing total mastectomy in breast carcinoma patients, assessing both oncological and aesthetic outcomes.

Methods: A retrospective analysis was conducted on 28 patients who underwent skin-sparing total mastectomy with preservation of the nipple-areola complex, followed by immediate breast reconstruction using implants and dermal flaps. Data on patient demographics, surgical outcomes, complications, and patient satisfaction were collected and analyzed.

Results: The study included 28 patients with an average age of 54.3 years. The implant sizes used ranged from 200 to 325 cc. Among these patients, 7 were chronic smokers and 8 had chronic diseases. A total of 22 patients underwent bilateral mastectomies, while 6 had unilateral mastectomies. Axillary lymph node dissection was performed in all cases. Preoperative radiotherapy was administered to 3 patients, and postoperative radiotherapy was given to 5 patients. Two patients experienced unilateral complete necrosis of the NAC and skin, while one patient had partial NAC necrosis. No evidence of capsular contracture, tumor recurrence, or metastasis was observed during the follow-up period. Patient satisfaction was high, with 24 out of 28 patients expressing positive outcomes.

Conclusion: Simultaneous implant and dermal flap breast reconstruction after skin-sparing total mastectomy offers a viable single-session approach with optimal cosmetic results, minimal morbidity, and high patient satisfaction. This technique is particularly beneficial for patients seeking immediate reconstruction with preserved nipple-areola complex.

The heterogeneity of the tumor microenvironment (TME) in breast cancer significantly influences therapeutic response and prognosis, yet noninvasive evaluation remains a clinical challenge. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), through multiparametric quantitative analysis (eg, K^trans, V_e, K_ep), enables dynamic characterization of tumor vascularization and perfusion heterogeneity. Concurrently, radiomics technology, leveraging high-throughput feature extraction and machine learning modeling, identifies potential biomarkers associated with TME biological properties. This review systematically examines the integration strategies of DCE-MRI multiparametric quantification and radiomics: first, elucidating the capability of DCE-MRI pharmacokinetic models to quantify microvascular heterogeneity, and delineating radiomics feature screening and predictive model construction based on 3D segmentation. Furthermore, it explores the combined application of these techniques in evaluating angiogenesis, resolving immune microenvironment dynamics, and mapping metabolic heterogeneity, with emphasis on clinical translational evidence in molecular subtype discrimination, treatment response prediction, and prognostic assessment. Key limitations persist in technical standardization (eg, 37% variability in Ktrans values across 1.5T/3.0T systems) and biological interpretability, with fewer than 40% of radiomics features linked to known molecular pathways. Future advancements demand multicenter data harmonization, radiogenomics integration, and digital twin technology to optimize personalized therapeutic navigation systems. This work provides methodological insights and technical innovation pathways for noninvasive TME heterogeneity assessment in breast cancer.

Male breast cancer (MBC) is a rare condition, comprising less than 1% of all breast cancer cases. This review examines the epidemiology, risk factors, clinical presentation, diagnostic approaches, and treatment strategies for MBC in both early and advanced stages. Early diagnosis of MBC poses a significant challenge, as men typically present with more advanced disease than women with breast cancer, likely due to limited awareness and delayed medical care. Data guiding treatment strategies remain limited, as most clinical trials have historically excluded male participants. This review provides a comprehensive analysis of recent advances in MBC, critically examines current diagnostic and therapeutic gaps, and outlines emerging research priorities. By emphasizing the limitations of existing evidence and the urgent need for male-specific clinical trials, this manuscript presents a forward-looking perspective aimed at fostering more inclusive research to develop tailored, evidence-based strategies for male patients.

Combining cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) with cyclin-dependent proteins can reduce the formation of cyclin D-CDK4/6 complexes, resulting in the inactivation of downstream genes and suppression of cell proliferation. Previous research on the use of CDK4/6 inhibitors in combination with endocrine therapies and anti-HER2 targeting agents across various subtypes and stages of breast cancer has shown promising outcomes in patient prognoses and tolerable drugs toxicities. For the present, the CDK4/6 inhibitors that have been widely used for the treatment of breast cancer are palbociclib, abemaciclib and ribociclib. Dalpiciclib (SHR6390), a novel and selective CDK4/6 inhibitor developed in China, has been approved by the National Medical Products Administration. The researches about dalpiciclib with different anti-tumor drugs are ongoing to explore the efficacy and the best strategies to use dalpiciclib. This review provides an overview of the research progress on dalpiciclib across different breast cancer subtypes with various anti-tumor drugs in different treatment opportunities.

Purpose: To explore the efficacy and safety of continuous administration of anlotinib combined with oral vinorelbine in refractory human epidermal growth factor-2 (HER2) negative advanced breast cancer (ABC).

Patients and methods: This retrospective study included 41 HER2 negative ABC patients who received anlotinib (8mg orally per day without interruption) plus oral vinorelbine during November 2019 and February 2023. These patients have received at least two treatments in the past. The efficacy and adverse events (AEs) of these patients need to be evaluated.

Results: The median follow-up time for this study was 35.6 months. Among 41 patients with HER2 negative ABC, 16 were HR positive/HER2 negative and 25 were triple negative breast cancer (TNBC). The median progression free survival (PFS) and overall survival (OS) were 6.7 months (95% CI, 4.9-8.5 months) and 28.3 months (95% CI, 10.6-46.0 months). There were no statistical differences in PFS (p=0.200) and OS (p=0.494) between the HR positive/HER2 negative and TNBC subgroups. The objective response rate (ORR), clinical benefit rate (CBR) and disease control rate (DCR) were 22.0%, 61.0% and 82.9%, respectively. Forty patients (97.6%) experienced varying grades of AEs and 31.7% of patients for grades 3-4. The most common grade 3-4 AEs that we observed were neutropenia (17.1%), leukopenia (9.8%) and diarrhea (9.8%).

Conclusion: Continuous administration of anlotinib combined with oral vinorelbine demonstrates to be efficacious and well tolerated for refractory HER2 negative ABC.

Background: Interval breast cancers (IBCs) are detected between regular mammographic screenings after an initially negative result. Studies have shown that the prognosis of IBCs is similar to that of unscreened symptomatic cancers and is hence a surrogate used to assess the effectiveness of screening programs. This systematic review consolidates the current literature available on strategies to reduce the rates of IBC.

Methods: Following PRISMA guidelines, three databases were searched from inception till October 29, 2023 to identify papers, which reported IBC rates. Key search terms included "interval breast cancer", "mammogram", "tomosynthesis" and "screening".

Results: A total of 32 articles were included. Fourteen studies discussed the use of digital breast tomosynthesis (DBT) as an alternative screening modality to mammograms. Six studies discussed the use of artificial intelligence (AI) on mammograms, five studies discussed the use of supplemental modalities including ultrasonography (US) in addition to mammograms, five studies discussed varying screening intervals and two studies discussed tamoxifen use.

Conclusion: The trajectory of IBCs can be altered by early detection when they are more amenable to treatment, through advanced screening techniques, adjusting inter-screening intervals and modifiable risk factors. The goal is to create a screening protocol that is economically effective and accessible to various populations.

Triple-negative breast cancer (TNBC) represents a particularly aggressive and heterogeneous subtype of breast cancer, associated with poor prognosis and limited treatment options. This review delves into the rising incidence of TNBC, particularly among younger women, and explores the significant demographic disparities that contribute to variations in incidence, treatment access and survival outcomes. We provide a discussion of TNBC's molecular and genetic landscape, including key pathways revolving around TP53, BRCA1/2 mutations, and PI3K/AKT signaling, which have informed the development of targeted therapies. Recent practice-changing studies are highlighted, which have resulted in the integration of immune checkpoint inhibitors in both early-stage and metastatic settings, the application of PARP inhibitors for BRCA-mutated TNBC and the introduction of antibody-drug conjugates as valuable new therapeutic options. We also review the role of neoadjuvant chemotherapy, novel biomarkers such as tumor-infiltrating lymphocytes, and advancements in diagnostic tools, including machine learning-based imaging and spatial transcriptomics, which are all driving shifts towards personalized approaches. This review synthesizes emerging research and major changes in clinical practice to provide a concise overview of the recent innovations and upcoming trends in TNBC diagnosis and therapy.

Breast cancer (BC) is the most common type of cancer among women worldwide. A large number of studies have found that the high expression or dysregulation of cyclin-dependent protein kinases (CDKs) is closely associated with breast cancer. For example, the CDK4/6-Rb axis is involved in the G1/S phase transition of the cell cycle and plays an important role in BC; CDK1 and its associated cyclin are commonly involved in mitotic progression, and increased expression of CDK1-associated cyclin has been observed in BC; loss of CDK12 significantly ameliorates triple-negative breast cancer. CDKs are one of the major families within the group of PROteolysis Targeting Chimeras (PROTACs)-degraded kinases. PROTAC is a potent technology for protein-targeted degradation, whose molecules consist of the ligand of the Protein of Interest (POI), the ligand of the E3 ubiquitin ligase (E3), and a Linker. After binding to POI, PROTAC can recruit E3 to ubiquitinate POI via ubiquitin-proteasome mediated degradation. In this review, we summarize relevant research results and review that PROTAC can effectively inhibit the proliferation of breast cancer cells by inducing ubiquitination of CDK1, CDK4/6, CDK9, CDK12/13 and their subsequent degradation by proteasomes, which is expected to be a novel approach for the treatment of breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive malignancy with high metastasis and recurrence rates. Current treatments like chemotherapy and immunotherapy face challenges due to chemotherapy side effects, limited immunotherapy applicability, and TNBC's immunosuppressive microenvironment.

Purpose: To achieve a more effective treatment for TNBC, a novel therapeutic strategy has been developed, which uses X-ray excited photodynamic therapy (X-PDT) to activate the tumor immune microenvironment following with the immunotherapy of Anti-CTLA4.

Methods: Base on the 4T1 tumor mouse model, this study initially investigated the regulatory effects of X-PDT on the tumor immune microenvironment. Subsequently, the therapeutic efficacy of combining X-PDT with Anti-CTLA4 was evaluated for its inhibitory effects on primary, metastatic, and recurrent tumors. The underlying mechanisms were further elucidated through comprehensive techniques including flow cytometry, ELISA, and immunofluorescence assays.

Results: The synergistic strategy can effectively ablate the primary tumor while inhibiting metastasis and preventing recurrence like a vaccine. It enhances intratumoural dendritic cells (DCs) maturation (from 25.7% to 58.3%, P < 0.05) and immune T cell infiltration activating a strong anti-tumor immune response. The anti-tumor efficacy of synergistic therapy is enhanced by 2.5 times comparing with immunotherapy alone, while the tumor metastasis has been inhibited significantly. The maturation level of mature dendritic cells was increased from 26.7% to 86.3% (P < 0.01). The intratumoural CD8⁺/CD4⁺ T cells were increased from 0.51% and 1.54% to 15.4% and 23.1% (P < 0.0001), respectively. The synergistic therapy exerts a powerful vaccine-like long-term immune memory function to prevent tumor recurrence with the elevated level of effector memory T (Tem) cells (from 12.8% to 33.3%, P < 0.05).

Conclusion: Based on the 4T1 mouse model, developed an effective vaccine-like therapeutic strategy combining X-PDT with Anti-CTLA4, which can effectively ablate tumors, inhibit metastasis, and prevent tumor recurrence. This work may provide a novel effective therapeutic modality for the clinical treatment of TNBC.