Breast Cancer Progression Research Articles

The RNA-binding protein LSM family regulating reproductive development via different RNA metabolism.

The RNA-binding protein LSM family regulating reproductive development via different RNA metabolism.

NHERF2 regulatory function in signal transduction pathways and control of gene expression: Implications for cellular homeostasis and breast cancer.

NHERF2 regulatory function in signal transduction pathways and control of gene expression: Implications for cellular homeostasis and breast cancer.

A Review Unveiling the Ferroptosis-Regulated Cell Signalling Pathways in Breast Cancer to Elucidate Potent Targets for Cancer Management.

Recent research suggests that targeting ferroptosis exhibits promise as a potent treatment approach for breast carcinoma. Specific subtypes of tumor cells exhibit heightened vulnerability to ferroptosis-inducing chemicals, which selectively trigger tumor stem cells' demise, enhance tumor cells' sensitivity to chemotherapeutic drugs, and eliminate cancerous cells. Ferroptosis plays a dual role in breast cancer progression, emerging as both a stimulating and inhibitory component. Ferroptosis is effective in treating cancer cells (mesenchymal breast), identified by their ability to undergo Epithelial-mesenchymal Transition (EMT) and their resistance to conventional therapies. Pharmaceutical drugs that hinder the activity of enzymes known as kinases, which are involved in the AKT/mTOR/PI3K signaling pathway, have shown significant potential in the treatment of breast carcinoma. This review investigates the molecular mechanisms of different signaling pathways implicated in ferroptosis in breast carcinoma, with specific emphasis on metastasis, invasion, and proliferation. Our study contributes to understanding a potentially important target that could be used in developing therapeutic strategies for breast cancer treatment.

IL6 mediated cFLIP downregulation increases the migratory and invasive potential of triple negative breast cancer cell.

IL6 mediated cFLIP downregulation increases the migratory and invasive potential of triple negative breast cancer cell.

Autophagy signaling mediated by non-coding RNAs: Impact on breast cancer progression and treatment.

Autophagy signaling mediated by non-coding RNAs: Impact on breast cancer progression and treatment.

Pharmacological modulation of cellular senescence: Implications for breast cancer progression and therapeutic strategies.

Pharmacological modulation of cellular senescence: Implications for breast cancer progression and therapeutic strategies.

Impact of surgical delay beyond 8 weeks on tumor progression and lymph node involvement in early breast cancer: Insights from the KHRONOS Project.

e12552 Background: Recent evidence highlights a potential negative impact of delaying surgery for early breast cancer (BC) beyond 8 weeks; however, the interplay between tumor biology and timing remains underexplored. This study investigates the role of surgical delay on tumor progression and lymph node (LN) involvement, emphasizing the biological heterogeneity of BC. Methods: This retrospective cohort study analyzed data from 924 early-stage BC patients (pts) (2015-2023). 267 pts underwent PAM50 testing to determine their intrinsic subtype. Patients had no initial radiological LN involvement and underwent primary surgery. Tumor progression and nodal status transition (N0 to N+) were analyzed based on surgical timing (≤ 8 weeks vs. > 8 weeks). Chi-square and ANOVA tests were employed to assess associations between clinicopathologic variables and outcomes. Results: 664 pts in our cohort (71.9%) underwent breast-conserving surgery, while 260 pts (28.1%) were treated with mastectomy. A total of 204 pts (22.08%) had a G3 tumor grade. The majority of tumors (784 pts; 84.89%) were smaller than 5 cm, as determined by mammography. Among the 267 pts who underwent the PAM50 test, 260 pts were classified within the luminal intrinsic subtype (141 pts as Luminal A and 120 pts as Luminal B). No significant differences were observed in tumor size progression or lymph node involvement between pts who underwent surgery within 8 weeks and those who experienced delays (p > 0.05). Subgroup analysis revealed that pts with G3 tumors had a higher likelihood of nodal progression when surgery was delayed (37.8% vs. 23.8%, p = 0.034). Additionally, the Luminal B subtype demonstrated increased nodal involvement associated with surgical delays (7,1% vs. 20,4%, p = 0.037). Conclusions: The subgroup of high-risk pts (G3) and luminal intrinsic subtype B may be associated with increased lymph node involvement following a surgical delay of > 8 weeks. These findings emphasize the importance of tumor biology in surgical prioritization and highlight the necessity for strategies to minimize delays in high-risk pts.

Hemoglobin level and neutrophil-to-lymphocyte ratio as prognostic peripheral blood markers of survival outcomes in sacituzumab govitecan therapy for mTNBC in Polish female cohort.

e13152 Background: Hemoglobin (Hb) level and the neutrophil-to-lymphocyte ratio (NLR) are key prognostic factors in breast cancer, influencing survival and disease progression. Anemia linked to tumor hypoxia, drive aggressive cancer behavior and reduce treatment efficacy, while elevated NLR reflects systemic inflammation and correlates with advanced disease. These factors may guide the use of novel therapies, such as sacituzumab govitecan (SG), which has significantly improved outcomes in metastatic triple-negative breast cancer (mTNBC). Identifying accessible prognostic markers is essential for optimizing treatment strategies in this challenging patient population. Methods: The study included 83 Polish women treated with SG across four oncological centers. Clinical data were collected retrospectively, and morphological parameters were assessed on day 1 of cycle I (D1CI). Hb was measured in grams per deciliter (g/dL), while N and L were measured in grams per liter (g/L). The NLR was determined by dividing the number of neutrophils by the number of lymphocytes. Anemia grades were defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Statistical analyses involved multivariate Cox regression for progression-free survival (PFS) and overall survival (OS). Results: The study included patients with a mean age of 55.07 years at the start of treatment. SG therapy was administered across multiple lines of treatment, with a median of 2 lines (range: 1–6) and a median of 5 completed cycles. The median PFS was 4.07 months, while the median OS was 8.01 months. Analysis of Hb levels revealed that at D1C1the distribution of hemoglobin levels was as follows: 35 patients (42.17%) had normal Hb levels, 33 patients (39.76%) had grade 1 and 15 patients (18.07%) had grade 2. The median Hb level was 11.7 g/dL (SD 1.55 g/dL), while the median NLR was 3.42 (SD 3.30). Multivariate Cox regression analysis identified Hb as a statistically significant predictor of PFS, with lower Hb levels associated with shorter PFS (HR: 0.8223, p = 0.0267). However, Hb was not a significant predictor of OS (p > 0.05). In contrast, higher NLR was significantly associated with reduced OS (HR: 1.1847, p = 0.0278). Conclusions: Lower levels of Hb are associated with reduced PFS, suggesting a significant impact of anemia on disease progression. Higher levels of NLR are associated with reduced OS, indicating that systemic inflammation might play a critical role in patient prognosis. These findings highlight the need for further evaluation of baseline Hb and NLR as prognostic factors in a larger population before initiating SG therapy.

MiRNA affects the advancement of breast cancer by modulating the immune system's response.

MiRNA affects the advancement of breast cancer by modulating the immune system's response.

Identification of key genes linking bisphenols exposure and breast cancer.

Identification of key genes linking bisphenols exposure and breast cancer.

The current landscape of aromatase inhibitors for the treatment of estrogen receptor-positive breast carcinoma.

The current landscape of aromatase inhibitors for the treatment of estrogen receptor-positive breast carcinoma.

LURAP1L-AS1 long noncoding RNA promotes breast cancer progression and associates with poor prognosis.

LURAP1L-AS1 long noncoding RNA promotes breast cancer progression and associates with poor prognosis.

Is progesterone receptor a neglected feature in breast cancer? A retrospective study analysing the clinicopathological characteristics of breast cancer based on progesterone receptor status

Is progesterone receptor a neglected feature in breast cancer? A retrospective study analysing the clinicopathological characteristics of breast cancer based on progesterone receptor status

Therapeutic potential of GNRHR analogs and SRC/FAK inhibitors to counteract tumor growth and metastasis in breast cancer.

Therapeutic potential of GNRHR analogs and SRC/FAK inhibitors to counteract tumor growth and metastasis in breast cancer.

Multiplex imaging reveals novel patterns of MRTFA/B activation in the breast cancer microenvironment

BackgroundBreast cancer progression and metastasis involve the action of multiple transcription factors in tumors and in the cells of the tumor microenvironment (TME) and understanding how these transcription factors are coordinated can guide novel therapeutic strategies. Myocardin-related transcription factors A and B (MRTFA/B also known as MKL1/2) are two related transcription factors that redundantly control cancer cell invasion and metastasis in mouse models of breast cancer, but their roles in human cancer are incompletely understood. Here, we investigated the expression and activation of these transcription factors to better assess their tumorigenic and metastatic impact on breast cancer and cells of the tumor microenvironment.MethodsWe used a multiplexed immunofluorescence approach to label MRTFA, MRTFB, tumor cells by using pan Cytokeratin, endothelial cells by using CD31, and antigen presenting cells (APCs) by using HLA-DRA on two different breast cancer tissue microarrays (TMA): The breast cancer progression TMA provided by the Cooperative Human Tissue Network (CHTN_BrCaProg3) and the University of Illinois Breast Cancer Working Group (TMA BCWG UIC-001-TMA) that included primary tumor and lymph node metastases from patients residing in the West Side and South Side of Chicago. We also used bioinformatics analyses of the TCGA and METABRIC databases and the Broad Institute’s single-cell RNA sequencing portal to investigate MRTFA/B expression patterns in the cells of the tumor microenvironment (TME).ResultsWe found that in human tumors, MRTFA/B are concurrently activated in cancer cells, but they show distinct patterns of expression across different histological subtypes and in the cells of the TME. Importantly, MRTFA expression was elevated in metastatic tumors of African American patients, who disproportionately die from breast cancer. Interestingly, in contrast to publicly available mRNA expression data, MRTFA was similarly expressed across estrogen receptor (ER) positive and negative breast tumors, while MRTFB expression was highest in ER+ breast tumors. Furthermore, MRTFA was specifically expressed in the perivascular antigen-presenting cells (APCs), which has been previously associated with immune suppression and breast cancer progression. We also found that MRTFA expression correlated with the expression of the immune checkpoint protein V-set immunoregulatory receptor (VSIR) in the TCGA data and found that MRTFA activity promotes VSIR expression in THP-1 monocytes and cultured HEK293 cells.ConclusionsOur results provide unique insights into how MRTFA and MRTFB promote metastasis in human cancer, the differences of their expression patterns, and their immune suppressive function within the breast cancer TME. Our results will guide future studies on targeting MRTFA/B transcriptional activity and the resulting immune suppression in breast cancer.Graphical

Oncogenic role of fumarate hydratase in breast cancer: metabolic reprogramming and mechanistic insights

Breast cancer remains the most prevalent malignancy among women globally, with its complexity linked to genetic variations and metabolic alterations within tumor cells. This study investigates the role of fumarate hydratase (FH), a key enzyme in the tricarboxylic acid (TCA) cycle, in breast cancer progression. Our findings reveal that FH mRNA and protein levels are significantly upregulated in breast cancer tissues and correlate with poor patient prognosis and aggressive tumor characteristics. Using in vitro and in vivo models, we demonstrate that FH overexpression enhances breast cancer cell proliferation, migration, and invasion through metabolic reprogramming and by increasing reactive oxygen species (ROS) production. Furthermore, we identify matrix metalloproteinase 1 (MMP1) as a downstream effector of FH, linked to p21 downregulation, elucidating a novel regulatory pathway influencing tumor behavior. Interestingly, unlike its tumor-suppressing role in other cancer types, this study highlights FH's oncogenic potential in breast cancer. Our results suggest that FH enhances cancer cell viability and aggressiveness via both catalytic and non-catalytic mechanisms. This work not only underscores the metabolic adaptations of breast cancer cells but also proposes FH as a potential biomarker and therapeutic target for breast cancer management.

Comprehensive advances in HER2-positive and HER2-negative breast cancer: unveiling molecular mechanisms and exploring cutting-edge targeted therapies for enhanced patient outcomes.

The human epidermal growth factor receptor (HER2), part of the tyrosine kinase family, serves as a key therapeutic target for patients with breast cancer, particularly those with HER2 overexpression. HER2 is overexpressed or amplified in approximately 15-20% of breast cancers. It includes HER1, HER2, HER3, and HER4, which progress the growth of cancerous cells. Key signaling pathways involved in HER2-driven breast cancer progression include the MAPK and mTOR pathways, which activate a cascade of factors that promote DNA synthesis and cell growth. A crucial process in HER2 cancer development is HER2 dimerization, which forms a functional oncogenic unit and is followed crucially by HER2:HER3 heterodimerization that leads to downstream signaling pathways. Alterations in the HER2 in solid tumors and ERBB2 gene mutations have led to advancements and implantation of precision-targeted approaches, as well as to combat the issues from the traditional approaches of targeting. In this review, we have thoroughly discussed different HER2-targeting therapies, which include monoclonal antibodies, antibody-drug conjugates, tyrosine kinase inhibitors, poly (ADP-ribose) polymerase inhibitors, CDK4/6 inhibitors, molecular probes targeting by PET/CT imaging, cancer vaccines, and cell therapies like CART-T and CAR-M cell therapy. Some of these targeted therapies have shown effectiveness in managing HER2-positive breast cancer and promoting tumor regression, while some remain under investigation for their potential benefits.

Synthesis, Anticancer Evaluation and Molecular Docking of Novel Imidazo[1,2-a]pyridine Derivatives

Imidazo[1,2-a]pyridine and its derivatives are widely recognized for their antifungal and anti-yeast activities, primarily through ergosterol synthesis inhibition. In this study, an efficient and high-yield synthesis route is presented for three novel imidazo[1,2-a]pyridine derivatives based on 1-(4-phenoxyphenyl)ethan-1-one. These compounds were synthesized by reacting 1-(4-phenoxyphenyl)ethan-1-one with pyridin-2-amine in presence of iodine as a cyclizing agent and ethanol. The structures of the synthesized compounds (A, B and C) were confirmed by spectroscopic techniques, including FT-IR, 1H NMR and 13C NMR. The molecular docking studies were conducted to evaluate their binding affinity toward oxidoreductase, a key enzyme in breast cancer progression, Compound C exhibited the highest binding energy (-9.207 kcal/mol) and interacted with essential amino acids (His 222, Tyr 216, Lys 270), anticancer activity was assessed against MCF7 (breast cancer) and PC3 (prostate cancer) cell lines using the MTT assay. These findings suggest that structural optimization enhances selectivity toward breast cancer cells, This study highlights the potential of tailored imidazo[1,2-a]pyridine derivatives as targeted therapies, particularly for breast cancer, further mechanistic and in vivo investigations are warranted to validate their selectivity and safety profiles.

The role of the gut microbiota in shaping the tumor microenvironment and immunotherapy of breast cancer

Breast cancer is the most prevalent malignancy among women worldwide and is a major contributor to cancer-related mortality. The tumor microenvironment (TME), composed of tumor cells, immune infiltrates, fibroblasts, and vascular components, is critically involved in tumor initiation, metastatic progression, and therapeutic response. In recent years, therapies targeting the TME have undergone rapid advancements, with the objective of enhancing antitumor immunity. Concurrently, mounting evidence underscores the pivotal role of the gut microbiota and its metabolites in modulating host immunity, influencing metabolic homeostasis, inflammation, and immune equilibrium. The composition and diversity of the gut microbiome influence breast cancer progression and patients’ responses to immunotherapy. Therefore, modulating the gut microbiota is a promising strategy to enhance the clinical outcomes of TME-targeted immunotherapies. In this review, we discuss the influence of gut microbiota and its derived metabolites on breast cancer progression and immunotherapy prognosis and explore potential strategies to optimize immunotherapy through gut microbiota modulation.

Breast Cancer Characteristics after Metabolic and Bariatric Surgery: A Matched Comparison to Patients with Severe Obesity.

Severe obesity increases breast cancer (BC) risk and progression. Metabolic and Bariatric Surgery (MBS) modulates metabolic and hormonal pathways, potentially influencing cancer biology. This study evaluates BC patients after MBS. The aim of this study is to assess the impact of MBS on BC, focusing on disease-free survival (DFS), presentation, subtypes, and oncologic outcomes. A retrospective analysis of a single-center database included patients undergoing BC surgery after MBS (2012-2020), matched (1:4) to patients with severe obesity undergoing BC surgery. Among 696 patients, 29 (4%) had BC post-MBS. Sleeve gastrectomy was the most common procedure (48.2%). Mean age at BC surgery was 60.7 ± 10 years. BMI prior to BC surgery was lower in the MBS-group (32.4 vs. 38.3 kg/m2, p < 0.0001). Disease-free survival (114 vs. 146 months, p = 0.75) and recurrence rates were similar. The MBS-group had lower luminal-A subtype rates (34.4% vs. 59.5%, p = 0.01) and higher luminal-B subtype rates (58.6% vs. 27.6%, p = 0.001). No patients in the MBS-group had ductal carcinoma in situ (DCIS) (0% vs. 20%, p = 0.03). Other subtypes showed no differences. MBS may influence BC pathogenesis, with lower DCIS and luminal-A rates. These findings suggest a potential reduction in overall BC incidence due to metabolic and hormonal changes after MBS. Oncologic outcomes remained comparable.