Epidemiology, clinical outcomes, and unmet needs of patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases: A systematic literature review

Müller, Volkmar; Bartsch, Rupert; Lin, Nancy U.; Montemurro, Filippo; Pegram, Mark D.; Tolaney, Sara M.

doi:10.1016/j.ctrv.2023.102527

Cited by 6 publications

(3 citation statements)

References 82 publications

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“…Yet, the presence of a drug with efficacy both within the brain and beyond could profoundly transform the multidisciplinary care of patients with HER2-positive metastatic breast cancer and brain metastases. Implementing a personalized treatment strategy that involve surgery, radiotherapy, and systemic treatments based on individual patient characteristics has the potential to enhance prognosis and quality of life [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

“Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper”

Conte,

Ciruelos,

Curigliano

et al. 2024

The Breast

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Section: Discussionmentioning

confidence: 99%

“…However, the current landscape compels to address the unmet challenges arising in the wake of disease progression. Particularly, the threat of brain metastases emerges as a critical concern, necessitating a move towards more tailored interventions [ [6] , [7] , [8] ].…”

Section: Introductionmentioning

confidence: 99%

“Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper”

Conte,

Ciruelos,

Curigliano

et al. 2024

The Breast

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“…Clinical categorization of breast cancer into Luminal A, Luminal B, HER2 overexpression, and triple-negative subtypes, based on ER, PR, HER2, and Ki67, has guided therapeutic decisions [ 4 , 5 ]. However, breast cancer's complexity and heterogeneity across individuals have posed significant challenges [ 6 , 7 ]. Currently, surgery, radiation, and endocrine therapy constitute the mainstay treatments for BRCA.…”

Section: Introductionmentioning

confidence: 99%

Spatial and single-cell explorations uncover prognostic significance and immunological functions of mitochondrial calcium uniporter in breast cancer

Li,

Tzeng,

Hsiao

et al. 2024

Cancer Cell Int

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The mitochondrial calcium uniporter (MCU) is a transmembrane protein facilitating the entry of calcium ions into mitochondria from the cell cytosol. Maintaining calcium balance is crucial for enhancing cellular energy supply and regulating cell death. The interplay of calcium balance through MCU and the sodium-calcium exchanger is known, but its regulation in the breast cancer tumor microenvironment remains elusive. Further investigations are warranted to explore MCU’s potential in BRCA clinical pathology, tumor immune microenvironment, and precision oncology. Our study, employing a multi-omics approach, identifies MCU as an independent diagnostic biomarker for breast cancer (BRCA), correlated with advanced clinical status and poor overall survival. Utilizing public datasets from GEO and TCGA, we discern differentially expressed genes in BRCA and examine their associations with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. Spatial transcriptomics is employed to investigate MCU gene expression in various regions of BRCA, while spatial transcriptomics and single-cell RNA-sequencing methods explore the correlation between MCUs and immune cells. Our findings are validated through the analysis of 59 BRCA patient samples, utilizing immunohistochemistry and bioinformatics to examine the relationship between MCU expression, clinicopathological features, and prognosis. The study uncovers the expression of key gene regulators in BRCA associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators positively correlate with different immune cells in six immune datasets, playing a pivotal role in immune cell infiltration in BRCA. Notably, high MCU performance is linked to CD8 + T cells infiltration in BRCA. Furthermore, pharmacogenomic analysis of BRCA cell lines indicates that MCU inactivation is associated with increased sensitivity to specific small molecule drugs. Our findings suggest that MCU alterations may be linked to BRCA progression, unveiling new diagnostic and prognostic implications for MCU in BRCA. The study underscores MCU's role in the tumor immune microenvironment and cell cycle progression, positioning it as a potential tool for BRCA precision medicine and drug screening.

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The VISTA/VSIG3/PSGL-1 axis: crosstalk between immune effector cells and cancer cells in invasive ductal breast carcinoma

Olbromski,

Mrozowska,

Piotrowska

et al. 2024

Cancer Immunol Immunother

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A checkpoint protein called the V-domain Ig suppressor of T cell activation (VISTA) is important for controlling immune responses. Immune cells that interact with VISTA have molecules, or receptors, known as VISTA receptors. Immune system activity can be modified by the interaction between VISTA and its receptors. Since targeting VISTA or its receptors may be beneficial in certain conditions, VISTA has been studied in relation to immunotherapy for cancer and autoimmune illnesses. The purpose of this study was to examine the expression levels and interactions between VISTA and its receptors, VSIG3 and PSGL-1, in breast cancer tissues. IHC analysis revealed higher levels of proteins within the VISTA/VSIG3/PSGL-1 axis in cancer tissues than in the reference samples (mastopathies). VISTA was found in breast cancer cells and intratumoral immune cells, with membranous and cytoplasmic staining patterns. VISTA was also linked with pathological grade and VSIG3 and PSGL-1 levels. Furthermore, we discovered that the knockdown of one axis member boosted the expression of the other partners. This highlights the significance of VISTA/VSIG3/PSGL-1 in tumor stroma and microenvironment remodeling. Our findings indicate the importance of the VISTA/VSIG3/PSGL-1 axis in the molecular biology of cancer cells and the immune microenvironment.

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Epidemiology, clinical outcomes, and unmet needs of patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases: A systematic literature review

Cited by 6 publications

References 82 publications

“Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper”

“Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper”

Spatial and single-cell explorations uncover prognostic significance and immunological functions of mitochondrial calcium uniporter in breast cancer

The VISTA/VSIG3/PSGL-1 axis: crosstalk between immune effector cells and cancer cells in invasive ductal breast carcinoma

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