Triple negative breast cancer

Glycosylation alterations in TNBC have significant implications for tumor behavior, diagnosis, prognosis, and therapeutic strategies. Dysregulated glycosylation affects cell adhesion, signaling, immune recognition, and response to therapy in TNBC. Different types of glycosylation, including N-linked glycosylation, O-linked glycosylation, glycosphingolipid glycosylation, mucin-type glycosylation, and sialylation, play distinct roles in TNBC. The "barcoding" method based on glycosylation sites of the membrane type mannose receptor (MR) shows promise in accurately distinguishing breast cancer subtypes, including TNBC...

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton...

The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development...

A promising alternative for cancer treatment involves targeted inhibition of the epigenetic regulator bromodomain-containing protein 4 (BRD4); however, available BRD4 inhibitors are constrained by their potency, oral bioavailability, and cytotoxicity. Herein, to overcome the drawback of the translational BRD4 inhibitors, we describe a novel BRD4-p53 inhibitor, SDU-071, which suppresses BRD4 interaction with the p53 tumor suppressor and its biological activity in MDA-MB-231 triple-negative breast cancer (TNBC) cells in vitro and in vivo...

INTRODUCTION: The most widespread female malignancy is breast cancer (BC), considerable percentage of patients with triple-negative BC (TNBC) experience rapid progression, recurrence, and metastasis. BC has not historically been treated as an immunogenic cancer. Nonetheless, several researchers have started to concentrate on immunotherapy. AIM: The aim of the study is to investigate the immunohistochemical (IHC) expression of programmed death-ligand 1 (PD-L1) by stromal tumor-infiltrating lymphocytes (TILs) and tumor cells (TC) in female (TNBC) and to correlate with pathological features of such tumors, particularly those determine biologic behavior, such as the grade and stage the overall survival...

BACKGROUND: This study investigated the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant systemic therapy (NAST) in patients with initially high nodal burden. METHODS: In the multicenter retrospective cohort, 388 individuals with cN1-3 breast cancer who underwent NAST and had SLNB followed by completion axillary lymph node dissection were included. In an external validation cohort, 267 patients with HER2+ or triple-negative breast cancer (TNBC) meeting similar inclusion criteria were included...

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) play a critical role in regulating TNBC tumor development. This study aimed to identify and characterize a specific subtype of CAFs associated with TNBC. Initially, using high-throughput bulk transcriptomic data in two cohorts, we identified three CAF-related subtypes (CS1, CS2, CS3) in TNBC samples. These three CAFs subtypes were closely linked to the tumor microenvironment. The CS1 subtype exhibited a relatively immune-rich microenvironment and a favourable prognosis, whereas the CS3 subtype displayed an immune-deprived tumor microenvironment and an unfavourable prognosis...

Taurine (Tau) has been found to inhibit triple-negative breast cancer (TNBC) invasion and metastasis. However, its effect on tumor-promoting macrophages and tumor suppressor macrophages in breast cancer progression remains unknown. In this study, we investigated the effects of Tau on macrophage polarization and its role in TNBC cell growth, invasion, and metastasis. We induced human THP-1 monocytes to differentiate into M2 macrophages through exogenous addition of interleukin-4. We used the TNBC cell lines MDA-MB-231 and BT-549 cultured in a conditioned medium from M2 macrophages to investigate the effect of Tau on tumor growth and invasion...

PURPOSE: Several recurring pathogenic variants (PVs) in BRCA1/BRCA2 and additional cancer susceptibility genes are described in the ethnically diverse Israeli population. Since 2019, testing for these recurring PVs is reimbursed unselectively for all patients with breast cancer (BC) in Israel. The aim was to evaluate the yield of genotyping for these PVs in non-Ashkenazi Jewish (AJ) patients with BC diagnosed ≥age 50 years. METHODS: Clinical and genotyping data of all patients with BC undergoing oncogenetic counseling at the Oncology Institute at Sheba Medical Center from June 2017 to December 2023 were reviewed...

Homologous recombination (HR) related gene alterations are present in a significant subset of prostate, breast, ovarian, pancreatic, lung and colon cancers rendering these tumors as potential responders to specific DNA damaging agents. A small molecule acylfulvene prodrug, LP-184, metabolizes to an active compound by the oxidoreductase activity of enzyme Prostaglandin Reductase 1 (PTGR1), which is frequently elevated in multiple solid tumor types. Prior work demonstrated that cancer cell lines deficient in a spectrum of (DNA damage repair) DDR pathway genes show increased susceptibility to LP-184...

Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target...

PURPOSE: Although ongoing studies are assessing the efficacy of new systemic therapies for patients with triple negative breast cancer (TNBC), the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival. METHODS: We used our prospective patient registry to evaluate data from 2012 to 2023...

PURPOSE: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study. PATIENTS AND METHODS: Patients with a complete response (CR), partial response (PR), or stable disease (SD) after at least 3 cycles of chemotherapy for HER2-negative breast cancer received pembrolizumab, regardless of programmed death-ligand 1 expression...

PURPOSE: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not...

Breast cancer, as one of the most common malignancies in women, exhibits complex and heterogeneous pathological characteristics across different subtypes. Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are two common and highly invasive subtypes within breast cancer. The stability of the breast microbiota is closely intertwined with the immune environment, and immunotherapy is a common approach for treating breast cancer.Tertiary lymphoid structures (TLSs), recently discovered immune cell aggregates surrounding breast cancer, resemble secondary lymphoid organs (SLOs) and are associated with the prognosis and survival of some breast cancer patients, offering new avenues for immunotherapy...

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B)...

The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD-L1) expression, as quantified by combined positive score (CPS; PD-L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple-negative breast cancer (mTNBC) in the phase 3 KEYNOTE-119 study. This exploratory analysis was conducted to determine whether the expression of PD-L1 on tumour cells contributes to the predictive value of PD-L1 CPS in mTNBC...

BACKGROUND: Chemoresistance and immunosuppression are two major obstacles in the current anti-cancer treatments. This study investigates the involvements of a CCAAT enhancer binding protein delta (CEBPD)/vesicle associated membrane protein 3 (VAMP3) axis in paclitaxel (PTX) resistance and immune evasion in triple-negative breast cancer (TNBC). METHODS: PTX resistance-related genes were screened by bioinformatics. CEBPD and VAMP3 expression in clinical TNBC samples was examined by immunohistochemistry...

BACKGROUND: The accurate prediction of pathological complete response (pCR) in the breast and axillary lymph nodes (ALN) before neoadjuvant chemotherapy (NAC) is of utmost importance for the development of treatment strategies. We aim to construct a nomogram on ultrasound (US) and clinical-pathologic factors to predict breast and ALN pCR in node-positive triple-negative breast cancers (TNBCs). METHODS: Patients identified with TNBCs from institution 1 (n = 328) were used for training cohort and those from institution 2 (n = 192) were for validation cohort...

Breast cryoablation for palliative and curative treatment of breast cancer has been performed for decades. Although there is a recent resurgence of interest in breast cryoablation with curative intent for unifocal, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, this report highlights the essential role that cryoablation can play in the palliative treatment of multicentric oestrogen and progesterone receptor-negative and human epidermal growth factor receptor 2-negative (triple-negative) breast cancer, meeting the select pretreatment objectives such as breast or nipple pain relief and prevention of tumour erosion through the skin or nipple in patients who have failed or cannot tolerate the standard of care treatment...