Heterogeneity breast metastasis

Metastasis remains a major challenge in treating breast cancer. Breast tumors metastasize to organ-specific locations such as the brain, lungs, and bone, but why some organs are favored over others remains unclear. Breast tumors also show heterogeneity, plasticity, and distinct microenvironments. This contributes to treatment failure and relapse. The interaction of breast cancer cells with their metastatic microenvironment has led to the concept that primary breast cancer cells act as seeds, whereas the metastatic tissue microenvironment (TME) is the soil...

Breast cancer, a leading cause of cancer-related deaths globally, exhibits distinct subtypes with varying pathological, genetic, and clinical characteristics. Despite advancements in breast cancer treatments, its histological and molecular heterogeneity pose a significant clinical challenge. Triple-negative breast cancer (TNBC), a highly aggressive subtype lacking targeted therapeutics, adds to the complexity of breast cancer treatment. Recent years have witnessed the development of advanced 3D culture technologies, such as organoids and spheroids, providing more representative models of healthy human tissue and various malignancies...

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype characterised by extensive intratumoral heterogeneity, high rates of metastasis and chemoresistance, leading to poor clinical outcomes. Despite progress, the mechanistic basis of chemotherapy resistance in TNBC patients remains poorly understood. Here, leveraging single-cell transcriptome datasets of matched longitudinal TNBC chemoresponsive and chemoresistant patient cohorts, we unravel distinct cell subpopulations intricately associated with chemoresistance and the signature genes defining these populations...

BACKGROUND: Metastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood...

Cancer-associated fibroblasts (CAFs) are prevalent in the tumor microenvironment of breast cancer, comprising a group of cell subpopulations with spatial, phenotypic, and functional heterogeneity. Due to the lack of specific markers for CAF subpopulations, their specific mechanisms in breast cancer remain unclear. We identified eight distinct CAF phenotypes in breast cancer using multiple single-cell RNA sequencing datasets and determined distinct transcription factors (TFs) of CAFs through SCENIC analysis...

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is especially aggressive and associated with high metastasis. The aetiology of TNBC is heterogeneous and characterised by multiple different mutations that amongst others cause constitutive and dysregulated MAPK and PI3K signalling. Additionally, in more than 50% of TNBC patients, the epidermal growth factor receptor (EGFR) is overexpressed and constitutively active. The multi-site docking protein Grb2-associated binder 1 (Gab1) is a central signalling hub that connects MAPK and PI3K signalling...

Extracellular vesicles (EVs) have been implicated in metastasis and proposed as cancer biomarkers. However, heterogeneity and small size makes assessments of EVs challenging. Often, EVs are isolated from biofluids, losing spatial and temporal context and thus lacking the ability to access EVs in situ in their native microenvironment. This work examines the capabilities of label-free nonlinear optical microscopy to extract biochemical optical metrics of EVs in ex vivo tissue and EVs isolated from biofluids in cases of human breast cancer, comparing these metrics within and between EV sources...

Breast cancer is a heterogeneous set of carcinomas comprising a subgroup of invasive ductal carcinomas and numerous infrequent subtypes. Primary squamous cell carcinoma (SCC) breast is sporadic, accounting for less than 0.1% of all invasive subtypes. Primary metastases to soft tissues of the oral cavity are incredibly rare, amounting to 0.1% of oral malignancies. Diagnosing metastasis to the oral cavity is an enigma to clinicians without pathognomonic signs and symptoms. Here, we report a case of SCC breast, who developed metastatic deposits in the left upper lip after a disease-free survival of 1 year...

BACKGROUND: Correct classification of estrogen receptor (ER) status is essential for prognosis and treatment planning in patients with breast cancer (BC). Therefore, it is recommended to sample tumor tissue from an accessible metastasis. However, ER expression can show intra- and intertumoral heterogeneity. 16α-[18 F]fluoroestradiol ([18 F]FES) Positron Emission Tomography/Computed Tomography (PET/CT) allows noninvasive whole-body (WB) identification of ER distribution and is usually performed as a single static image 60 min after radiotracer injection...

With a lack of targeted therapy and significantly high metastasis, heterogeneity, and relapse rates, Triple-Negative Breast Cancer (TNBC) offers substantial treatment challenges and demands more chemotherapeutic interventions. In the present study, indole-endowed thiadiazole derivatives have been synthesized and screened for antiproliferative potency against the triple-negative breast cancer MDA-MB-231 cell line. Compound 4h, possessing chlorophenyl moiety, displays the best anticancer potency (IC50: 0.43 μM) in the cell viability assay...

INTRODUCTION: Macrophages are innate immune cells that are associated with extensive phenotypic and functional plasticity and contribute to normal development, tissue homeostasis, and diseases such as cancer. In this review, we discuss the heterogeneity of tissue resident macrophages in the normal mammary gland and tumor-associated macrophages in breast cancer. Tissue resident macrophages are required for mammary gland development, where they have been implicated in promoting extracellular matrix remodeling, apoptotic clearance, and cellular crosstalk...

Spatiotemporal heterogeneity of tumors provides an escape mechanism for breast cancer cells, which can obstruct the investigation of tumor progression. While molecular profiling obtained from mass spectrometry imaging (MSI) is rich in biochemical information, it lacks the capacity for in vivo analysis. Ultrasound diagnosis has a high diagnostic accuracy but low chemical specificity. Here, we describe a noninvasive ultrasound elastography (UE)-guided MSI strategy (UEg-MSI) that integrates physical and biochemical characteristics of tumors acquired from both in vivo and in vitro imaging...

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous and clinically aggressive disease. Accumulating evidence indicates that tertiary lymphoid structures (TLSs) and tumor budding (TB) are significantly correlated with the outcomes of patients who have TNBC, but no integrated TLS-TB profile has been established to predict their survival. The objective of this study was to investigate the relationship between the TLS/TB ratio and clinical outcomes of patients with TNBC using artificial intelligence (AI)-based analysis...

BACKGROUND: To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment. METHODOLOGY: PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity...

Myeloid-derived suppressor cells (MDSCs) are key immunosuppressive cells in the tumor microenvironment (TME) that play critical roles in promoting tumor growth and metastasis. Tumor-associated platelets (TAPs) help cancer cells evade the immune system and promote metastasis. In this paper, we describe the interaction between MDSCs and TAPs, including their generation, secretion, activation, and recruitment, as well as the effects of MDSCs and platelets on the generation and changes in the immune, metabolic, and angiogenic breast cancer (BC) microenvironments...

The rapid metastasis & heterogenic constitution of triple negative breast cancer (TNBC) limits drug entry to the tumor, reducing treatment effectiveness. To address this, we have synthesized Casein nanoparticles (Cn NPs) with attached glutathione (GSH), a natural ligand for cancer cell overexpressed γ-glutamyl transpeptidase (GGT). Cn NPs encapsulated with Camptothecin and NIR dye IR 797 (CCN NPs) for combinatorial therapy of TNBC. The GSH-CCN nanoparticles (CCNG NPs) act as a Nano-Trojan to deceive the cancer cells by delivering therapeutic payloads directly to specific target cells...

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues...

Tumor budding is gaining importance as a prognostic factor in various carcinomas due to its association with epithelial-mesenchymal transition (EMT) and hence clinical outcome. Reporting tumor budding in breast cancer lacks homogeneity. We aim to systematically review the existing literature and conduct a meta-analysis to assess the prognostic implication of tumor budding in breast carcinoma. A systematic search was performed to identify studies that compared different prognostic variables between high- and low-grade tumor budding...

BACKGROUND: The aim of this study is an improved understanding of drug distribution in brain metastases. Rather than single point snapshots, we analyzed the time course and route of drug/probe elimination (clearance), focusing on the Intramural Periarterial Drainage (IPAD) pathway. METHODS: Mice with JIMT1-BR HER2+ experimental brain metastases were injected with biocytin-TMR and either trastuzumab or human IgG. Drugs/probes circulated for 5 min-48h, followed by perfusion...

BACKGROUND: Male breast cancer (MBC) accounts for one percent of all breast cancers. Due to the lack of awareness and routine screening programs, most patients present with systemic disease at the time of diagnosis with low overall survival. OBJECTIVES: This study aims to investigate the prognostic factors of male breast cancer and its correlation with established prognostic parameters and patient outcomes. METHODS: Thirty-eight male breast cancer patients are identified from the MKA Breast Cancer Clinic database, and their corresponding clinical and pathological characteristics are obtained...