Targeted Therapies for Triple-Negative Breast Cancer

Lyons, Tomas

doi:10.1007/s11864-019-0682-x

Cited by 264 publications

(187 citation statements)

References 36 publications

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“…A previous study showed that TNBC was more uneven on dynamic contrastenhanced MRI (29). Although the imaging modes used were The clinicopathology of tumors can reflect tumor biology and affect the outcome of chemotherapy in TNBC patients (30)(31)(32)(33). Our study found that the TNBC histological grade of the high TIL group was lower than that of the low TIL group (84%).…”

Section: Discussionmentioning

confidence: 47%

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Meng

Huang

et al. 2020

Front. Oncol.

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Objectives: Tumor-infiltrating lymphocytes (TILs) have been identified as a significant prognostic indicator of response to neoadjuvant therapy and immunotherapy for triple-negative breast cancer (TNBC) patients. Herein, we aim to assess the association between TIL levels and mammographic features in TNBC patients. Methods: Forty-three patients with surgically proven TNBC who underwent preoperative mammography from January 2018 to December 2018 were recruited. Pyradiomics software was used to extract 204 quantitative radiomics features, including morphologic, grayscale, and textural features, from the segmented lesion areas. The correlation between radiological characteristics and TIL levels was evaluated by screening the most statistically significant radiological features using Mann-Whitney U-test and Pearson correlation coefficient. The patients were divided into two groups based on tumor TIL levels: patients with TIL levels <50% and those with TIL levels ≥50%. The correlation between TIL levels and clinicopathological characteristics was assessed using the chi-square test or Fisher's exact test. Mann-Whitney U-test and Pearson correlation coefficient were used to analyze the statistical significance and Pearson correlation coefficient of clinical pathological features, age, and radiological features. Conclusion: Mammography features not only distinguish high and low TIL levels in TNBC patients but also can act as imaging biomarkers to enhance diagnosis and the response of patients to neoadjuvant therapies and immunotherapies.

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Section: Discussionmentioning

confidence: 47%

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Meng

Huang

et al. 2020

Front. Oncol.

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“…Many breast cancer cases associated with BRCA1 mutations are classified as TNBC as they do not show the expression of ER, PR and HER2. This kind of breast cancer is usually highly aggressive and difficult to treat [121]. A subset of sporadic TNBCs have defects in DNA repair and gene expression profiles typical of BRCA1-related cancers and they can be treated with therapeutic strategies based on deficiencies in DNA repair [122].…”

Section: Critical Role Of Brca1 and Tp53bp1 In Vd3 Signaling In Triplmentioning

confidence: 99%

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

Błasiak

Pawłowska

Chojnacki

et al. 2020

IJMS

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Several studies show that triple-negative breast cancer (TNBC) patients have the lowest vitamin D concentration among all breast cancer types, suggesting that this vitamin may induce a protective effect against TNBC. This effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis, inflammation, angiogenesis, invasion and metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated breast cancer type 1 susceptibility (BRCA1) gene, 1,25(OH)2D may induce protective effects by activating its receptor and inactivating cathepsin L-mediated degradation of tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in DNA double-strand break repair and contributing to genome stability. Similar effects can be induced by the interaction of 1,25(OH)2D with proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of vitamin D in TNBC to assess its preventive and therapeutic potential.

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“…For TNBC there are still no specific established therapies due to lack of defined targets, and radio-and chemotherapies are commonly used instead [15]. Additional potential therapeutic targets for personalized therapies have been identified (e.g., PI3KCA, EGFR, PARP, and PDL/PDL-1) [16][17][18]. Gene expression profiling classified BC into different molecular subtypes with distinct features and clinical outcomes: luminal A, luminal B, HER2-enriched, basal-like, claudin-low and normal-like subtypes [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer

Alday-Parejo

Richard

Wörthmüller

et al. 2020

Cancers

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Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates with ESR1 and luminal genes GATA3 and FOXA1 expression and better prognosis, while low MAGI1 levels correlates with higher histological grade, more aggressive phenotype and worse prognosis. Experimentally, MAGI1 downregulation in the ER+ human BC cells MCF7 impairs ER expression and signaling, promotes cell proliferation, and reduces apoptosis and epithelial differentiation. MAGI1 downregulation in the ER+ murine BC cell line 67NR accelerates primary tumor growth and enhances experimental lung metastasis formation. MAGI1 expression is upregulated by estrogen/ER, downregulated by prostaglandin E2/COX-2axis, and negatively correlates with inflammation in ER+/HER2− BC patients. Taken together, we show that MAGI1 is a new potential tumor suppressor in ER+/HER2− breast cancer with possible prognostic value for the identification of patients at high-risk of relapse within this subset.

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Targeted Therapies for Triple-Negative Breast Cancer

Cited by 264 publications

References 36 publications

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Vitamin D in Triple-Negative and BRCA1-Deficient Breast Cancer—Implications for Pathogenesis and Therapy

MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer

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