The Characteristics of Tumor Microenvironment in Triple Negative Breast Cancer

Fan, Yiqi; He, Shuai

doi:10.2147/cmar.s316700

Cited by 63 publications

(53 citation statements)

References 163 publications

(262 reference statements)

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“…The fact that the tumor microenvironment (TME) components and functions differ across the various subtypes of breast cancer is well-established [83]. Since the abundance of TAMs varies in different subtypes of breast cancer, the risk scores of these cases also varied accordingly (Supplementary Table S2).…”

Section: Discussionmentioning

confidence: 99%

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Jayasingam

Citartan

Zin

et al. 2022

IJMS

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The dysregulation of microRNAs (miRNAs) has been known to play important roles in tumor development and progression. However, the understanding of the involvement of miRNAs in regulating tumor-associated macrophages (TAMs) and how these TAM-related miRNAs (TRMs) modulate cancer progression is still in its infancy. This study aims to explore the prognostic value of TRMs in breast cancer via the construction of a novel TRM signature. Potential TRMs were identified from the literature, and their prognostic value was evaluated using 1063 cases in The Cancer Genome Atlas Breast Cancer database. The TRM signature was further validated in the external Gene Expression Omnibus GSE22220 dataset. Gene sets enrichment analyses were performed to gain insight into the biological functions of this TRM signature. An eleven-TRM signature consisting of mir-21, mir-24-2, mir-125a, mir-221, mir-22, mir-501, mir-365b, mir-660, mir-146a, let-7b and mir-31 was constructed. This signature significantly differentiated the high-risk group from the low-risk in terms of overall survival (OS)/ distant-relapse free survival (DRFS) (p value < 0.001). The prognostic value of the signature was further enhanced by incorporating other independent prognostic factors in a nomogram-based prediction model, yielding the highest AUC of 0.79 (95% CI: 0.72–0.86) at 5-year OS. Enrichment analyses confirmed that the differentially expressed genes were mainly involved in immune-related pathways such as adaptive immune response, humoral immune response and Th1 and Th2 cell differentiation. This eleven-TRM signature has great potential as a prognostic factor for breast cancer patients besides unravelling the dysregulated immune pathways in high-risk breast cancer.

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Section: Discussionmentioning

confidence: 99%

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Jayasingam

Citartan

Zin

et al. 2022

IJMS

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“…We demonstrated that the 3-gene TNBC score is related to TIL infiltration, where a lower score was associated with a high infiltration of TILs. This observation might be explained by the influence of CCL5 [ 36 , 37 ]. The expression of this gene causes a lowering of the score and, biologically, participates in the recruitment of TILs in TNBC [ 16 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Capability of TNBC 3-Gene Score among Triple-Negative Breast Cancer Subtypes

Araujo

Cruz-Ku

Cornejo

et al. 2022

Cancers

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Background: Triple-negative breast cancer (TNBC) is a complex and molecularly heterogeneous entity, with the poorest outcome compared with other breast cancer subtypes. Previously, we developed a TNBC 3-gene score with a significant prognostic capability. This study aims to test the 3-gene score in the different TNBC subtypes. Methods: Data from 204 TNBC patients treated with neoadjuvant chemotherapy were retrieved from public datasets and pooled (GSE25066, GSE58812, and GSE16446). After removing batch effects, cases were classified into Lehman’s TNBC subtypes and then the TNBC 3-gene score was used to evaluate the risk of distant recurrence in each subgroup. In addition, the association with tumor-infiltrating lymphocyte (TILs) levels was evaluated in a retrospective group of 72 TNBC cases. Results: The TNBC 3-gene score was able to discriminate patients with different risks within the pooled cohort (HR = 2.41 for high vs. low risk; 95%CI: 1.50–3.86). The score showed predictive capability in the immunomodulatory subtype (HR = 4.16; 95%CI: 1.63–10.60) and in the mesenchymal stem-like subtype (HR = 18.76; 95%CI: 1.68–208.97). In the basal-like 1, basal-like-2, and mesenchymal subtypes, the observed differential risk patterns showed no statistical significance. The score had poor predictive capability in the luminal androgen receptor subtype (p = 0.765). In addition, a low TNBC 3-gene score was related to a high level of TIL infiltration (p < 0.001). Conclusions: The TNBC 3-gene score is able to predict the risk of distant recurrence in TNBC patients, specifically in the immunomodulatory and mesenchymal stem-like subtype. Despite a small sample size in each subgroup, an improved prognostic capability was seen in TNBC subtypes with tumor-infiltrating components.

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“…TNBC has an immunogenic microenvironment that contains a variety of cell types, including tumour-infiltrating lymphocytes (TILs), tumour-associated macrophages (TAM), neutrophils and fibroblasts, and NK cells [ 23 ]. It has been found that tumours with high levels of TILs—including CD20+ B cells, CD4 and CD8+ T cells, and CD138+ plasma cells—have better pathological Complete Response (pCR), Disease-Free-Survival (DFS) and OS rates.…”

Section: Targeting Microenvironment (Angiogenesis and Immune System)mentioning

confidence: 99%

Personalised Therapies for Metastatic Triple-Negative Breast Cancer: When Target Is Not Everything

Capici¹,

Carlofrancesco

Nicole

et al. 2022

Cancers

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Triple-negative breast cancer—defined by the absence of oestrogen/progesterone receptors and human epidermal growth factor receptor 2 expression—is a complex and heterogeneous type of tumour characterised by poor prognosis, aggressive behaviour and lack of effective therapeutic strategies. The identification of new biomarkers and molecular signatures is leading to development of new therapeutic strategies including immunotherapy, targeted therapy and antibody-drug conjugates (ADCs). Against a background where chemotherapy has always been considered the standard of care, evolution towards a precision medicine approach could improve TNBC clinical practice in a complex scenario, with many therapeutic options and new drugs. The aim of this review was to focus on emerging therapeutic targets and their related specific therapy, discussing available and emerging drugs, underlining differences in approval by American and European regulatory authorities and showing the future perspective in the large number of ongoing clinical trials.

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The Characteristics of Tumor Microenvironment in Triple Negative Breast Cancer

Cited by 63 publications

References 163 publications

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Prognostic Capability of TNBC 3-Gene Score among Triple-Negative Breast Cancer Subtypes

Personalised Therapies for Metastatic Triple-Negative Breast Cancer: When Target Is Not Everything

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