Outcomes of Triple‐Negative Breast Cancers (TNBC) Compared with Non‐TNBC: Does the Survival Vary for All Stages?

Agarwal, Gaurav; Nanda, Gitika; Lal, Punita; Mishra, Anjali; Agarwal, Amit; Agrawal, Vinita; Krishnani, Narendra

doi:10.1007/s00268-016-3422-4

Cited by 78 publications

(73 citation statements)

References 39 publications

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“…TNBC accounts for 15%–20% of all breast cancers and is an especially aggressive and hard-to-treat disease 2. Women with TNBC are generally diagnosed at later stages, have a poorer prognosis and a higher recurrence risk compared with those diagnosed with non-TNBC 3.…”

Section: Introductionmentioning

confidence: 99%

Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1

Li¹,

Yan²,

Deng³

et al. 2017

OTT

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PurposeTriple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear.Materials and methodsThis experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs. We evaluated the activations of RhoA, Rac1 and Cdc42 in TNBC cells with a Rho activation assay. A panel of inhibitors of estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/HER2) treated non-TNBC (SK-BR-3 and MCF-7) cells and blocked the ER/PR/HER2 activity. Wound-healing assays and Rho activation assays were employed to measure the effect of kaempferol and ER/PR/HER2 inhibitors on Rho activation and cell migration rates.ResultsA low dose of kaempferol (20 μmol/L) had a potent inhibitory effect on the migration and invasion of TNBC cells, but not on the migration of non-TNBC (SK-BR-3 and MCF-7) cells. The low dose of kaempferol downregulated the activations of RhoA and Rac1 in TNBC cells. Moreover, the low dose of kaempferol also inhibited the migration and RhoA activations of HER2-silence SK-BR-3 and ER/PR-silence MCF-7 cells. Overexpressed HER2 rescued the cell migration and RhoA and Rac1 activations of kaempferol-treated MDA-MB-231 cells.ConclusionThe low dose of kaempferol inhibits the migration and invasion of TNBC cells via blocking RhoA and Rac1 signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1

Li¹,

Yan²,

Deng³

et al. 2017

OTT

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“…Triple‐negative breast cancer (TNBC) does not express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her‐2) gene, resulting in aggressive pathology, early peak of recurrence, and shorter overall survival than other subtypes. The lack of endocrine therapy and Her‐2 targeted agents; standard chemotherapy is the main method of systemic treatments . Therefore, it is necessary to investigate TNBC aggressive pathology mechanism and the potential therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

“…The lack of endocrine therapy and Her-2 targeted agents; standard chemotherapy is the main method of systemic treatments. [2][3][4] Therefore, it is necessary to investigate TNBC aggressive pathology mechanism and the potential therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Identification of tRNA‐derived small noncoding RNAs as potential biomarkers for prediction of recurrence in triple‐negative breast cancer

Feng

Chu

et al. 2018

Cancer Medicine

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Triple‐negative breast cancer (TNBC), an intrinsic subtype of breast cancer, is characterized by aggressive pathology and shorter overall survival. Yet there is no effective therapy for these patients. Breast cancer stem cells (BCSCs) in TNBC may account for treatment failure. It is urgent to identify new therapeutic targets for TNBC. tRNA‐derived small noncoding RNAs (tDRs) represent a new class of small noncoding RNAs (sncRNA), which have been reported in some human diseases and biological processes. However, there is no detailed information about the relationship between tDRs and BCSCs. In this study, a population of CD44+/CD24−/low cells was isolated and identified by reliable BCSC surface markers. tDR expression profiles in TNBC and non‐TNBC CSCs were performed by RNA sequencing. A total of 1327 differentially expressed tDRs contained 18 upregulated and 54 downregulated in TNBC group. Furthermore, the selected tDRs were validated by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). tDR‐000620 expression level was consistently lower in TNBC cell lines CSCs (all P < 0.05) and serum samples (t = 2.597, P = 0.013). tDR‐000620 expression was significant association with age (P = 0.018), node status (P = 0.026) and local recurrence (P = 0.019) by chi‐square test. Kaplan‐Meier method with log‐rank test for comparison of recurrence curves. The results showed that the tDR‐000620 expression (P = 0.002) and node status (P = 0.001) group were statistically significant with recurrence‐free survival. Furthermore, multivariate Cox regression demonstrated that lymphatic metastasis (HR, 3.616; 95% CI, 1.234‐10.596; P = 0.019) and low tDR‐000620 expression (HR, 0.265; 95% CI, 0.073‐0.959; P = 0.043) were two independent adverse predictive factors for recurrence‐free survival. Finally, we found that tDR‐000620 participated in some important biological processes though GO and KEGG analysis. Taken together, our study reveals the expression profiles of tDRs in TNBC and non‐TNBC CSCs. It offers helpful information to understand the tDR‐000620 expression is responsible for the aggressive phenotype of BCSCs. It may provide predictive biomarkers and therapeutic targets for TNBC recurrence.

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“…Consequently, TNBC results in the poorest overall survival of any other breast cancer subtype. 4 To achieve more successful prognoses, there is a clinical need to develop more tailored treatments against TNBC.…”

mentioning

confidence: 99%

CRISPR/Cas9‐mediated mutagenesis to validate the synergy between PARP1 inhibition and chemotherapy in BRCA1‐mutated breast cancer cells

Mintz

Lao

Chi

et al. 2020

Bioengineering & Transla Med

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For patients carrying BRCA1 mutations, at least one-third develop triple negative breast cancer (TNBC). Not only is TNBC difficult to treat due to the lack of molecular target receptors, but BRCA1 mutations (BRCA1m) also result in chemotherapeutic resistance, making disease recurrence more likely. Although BRCA1m are highly heterogeneous and therefore difficult to target, BRCA1 gene's synthetic lethal pair, PARP1, is conserved in BRCA1m cancer cells. Therefore, we hypothesize that targeting PARP1 might be a fruitful direction to sensitize BRCA1m cancer cells to chemotherapy. We used CRISPR/Cas9 technology to generate PARP1 deficiency in two TNBC cell lines, MDA-MB-231 (BRCA1 wild-type) and MDA-MB-436 (BRCA1m). We explored whether this PARP1 disruption (PARP1m) could significantly lower the chemotherapeutic dose necessary to achieve therapeutic efficacy in both a 2D and 3D tumor-on-a-chip model. With both BRCA1m and PARP1m, the TNBC cells were more sensitive to three representative chemotherapeutic breast cancer drugs, doxorubicin, gemcitabine and docetaxel, compared with the PARP1 wild-type counterpart in the 2D culture environment. However, PARP1m did not result in this synergy in the 3D tumor-on-a-chip model, suggesting that drug dosing in the tumor microenvironment may influence the synergy. Taken together, our results highlight a discrepancy in the efficacy of the combination of PARP1 inhibition and chemotherapy for TNBC treatment, which should be clarified to justify further clinical testing. K E Y W O R D S BRCA1, CRISPR/Cas9, PARP1, precision medicine, synthetic lethality, triple negative breast cancer Breast cancer is the leading cause of death in women worldwide. 1Around 12-17% of breast cancer patients have triple negative breast cancer (TNBC), 2 an aggressive, heterogeneous subtype characterized by the lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor Type 2 (HER2) expression.

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Outcomes of Triple‐Negative Breast Cancers (TNBC) Compared with Non‐TNBC: Does the Survival Vary for All Stages?

Cited by 78 publications

References 39 publications

Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1

Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1

Identification of tRNA‐derived small noncoding RNAs as potential biomarkers for prediction of recurrence in triple‐negative breast cancer

CRISPR/Cas9‐mediated mutagenesis to validate the synergy between PARP1 inhibition and chemotherapy in BRCA1‐mutated breast cancer cells

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