scholarly journals Targeted Therapeutic Strategies for Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Li ◽  
Zhijun Zhan ◽  
Xuemin Yin ◽  
Shujun Fu ◽  
Xiyun Deng

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, which is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR) expression and the absence of human epidermal growth factor receptor 2 (HER2) expression/amplification. Conventional chemotherapy is the mainstay of systemic treatment for TNBC. However, lack of molecular targeted therapies and poor prognosis of TNBC patients have prompted a great effort to discover effective targets for improving the clinical outcomes. For now, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi’s) and immune checkpoint inhibitors have been approved for the treatment of TNBC. Moreover, agents that target signal transduction, angiogenesis, epigenetic modifications, and cell cycle are under active preclinical or clinical investigations. In this review, we highlight the current major developments in targeted therapies of TNBC, with some descriptions about their (dis)advantages and future perspectives.

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 159-166 ◽  
Author(s):  
Frederik Marmé ◽  
Andreas Schneeweiss

Triple-negative breast cancer (TNBC) is a heterogeneous disease comprised of several biologically distinct subtypes. However, treatment is currently mainly relying on chemotherapy as there are no targeted therapies specifically approved for TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. New targeted approaches are, therefore, urgently needed. Currently, bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A antibody, is the only targeted agent with an approval for the therapy of metastatic breast cancer, but does not provide a specific benefit in the TNBC subtype. This review discusses the current clinical developments in targeted approaches for TNBC, including anti-angiogenic therapies, epidermal growth factor receptor (EGFR)-targeted therapies, poly(ADP-ribose) polymerase (PARP) inhibitors and platinum salts, as well as novel strategies using immune-checkpoint inhibitors, which have recently demonstrated first promising results. Strategies focusing on specific subtypes of TNBC like anti-androgenic therapies for the luminal androgen receptor subtype (LAR) and others are also discussed.


Plasma ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 218-228 ◽  
Author(s):  
Xiaoqian Cheng ◽  
Warren Rowe ◽  
Lawan Ly ◽  
Alexey Shashurin ◽  
Taisen Zhuang ◽  
...  

Triple-negative breast cancer is a phenotype of breast cancer where the expression level of estrogen, progesterone and human epidermal growth factor receptor 2 (HER2) receptors are low or absent. It is more frequently diagnosed in younger and premenopausal women, among which African and Hispanic have a higher rate. Cold atmospheric plasma has revealed its promising ant-cancer capacity over the past two decades. In this study, we report the first cold plasma jet delivered by the Canady Cold Plasma Conversion Unit and characterization of its electric and thermal parameters. The unit effectively reduced the viability of triple-negative breast cancer up to 80% without thermal damage, providing a starting point for future clinical trials.


Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.


Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1864 ◽  
Author(s):  
Holly Tovey ◽  
Maggie Chon U. Cheang

The concept of precision medicine has been around for many years and recent advances in high-throughput sequencing techniques are enabling this to become reality. Within the field of breast cancer, a number of signatures have been developed to molecularly sub-classify tumours. Notable examples recently approved by National Institute for Health and Care Excellence in the UK to guide treatment decisions for oestrogen receptors (ER)+ human epidermal growth factor receptor 2 (HER2)- patients include Prosigna® test, EndoPredict®, and Oncotype DX®. However, a population of still unmet need are those with triple negative breast cancer (TNBC). Accounting for 15–20% of patients, this population has comparatively poor prognosis and as yet no targeted treatment options. Studies have shown that some patients with TNBC respond favourably to DNA damaging drugs (carboplatin) or agents which inhibit DNA damage response (poly ADP ribose polymerase (PARP) inhibitors). Known to be a heterogeneous population, there is a need to identify further TNBC patients who may benefit from these treatments. A number of signatures have been identified based on association with treatment response or specific genetic features/pathways however many of these were not restricted to TNBC patients and as of yet are not common practice in the clinic.


2017 ◽  
Vol 13 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Vijayakrishna K. Gadi ◽  
Nancy E. Davidson

Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sabrina Bimonte ◽  
Marco Cascella ◽  
Antonio Barbieri ◽  
Claudio Arra ◽  
Arturo Cuomo

AbstractTriple-Negative Breast Cancer (TNBC), represents a subtype of breast cancer in which the estrogens receptor (ER) negative, the progesterone receptor (PR) negative and the human epidermal growth factor receptor 2 (HER2) negative, are not expressed. Thusly, TNBC does not respond to hormonal therapies or to those targeting the HER2 protein receptors. To overcome this flawed issue, new alternative therapies based on the use of natural substances, as the (−) - epigallocatechin 3-gallate (EGCG), has been proposed. It is largely documented that EGCG, the principal constituent of green tea, has suppressive effects on different types of cancer, including breast cancer, through the regulation of different signaling pathways. Thus, is reasonable to assume that EGCG could be viewed as a therapeutic option for the prevention and the treatment of TNBC. Here, we summarizing these promising results with the scope of turn a light on the potential roles of EGCG in the treatment of TNBC patients.


2012 ◽  
Vol 25 (3) ◽  
pp. 319-323 ◽  
Author(s):  
Carrie L. Griffiths ◽  
Jacqueline L. Olin

Triple negative breast cancer (TNBC), an aggressive variant of breast cancer, is characterized by lack of expression of the estrogen (ER) and progesterone receptors (PRs) and the human epidermal growth factor receptor (HER-2) that are commonly observed in other breast cancer subtypes. The TNBC subtype primarily occurs in younger women of African American or Hispanic descent and tumors tend to be high grade and initially responsive to chemotherapy. However, TNBC is characteristically aggressive with high recurrence, metastatic, and mortality rates. Treatment options are limited since the hormonal receptor and HER-2 antagonists typically used for other breast cancers are ineffective. As such, the mainstay of treatment of TNBC is traditional systemic cytotoxic chemotherapy. Potential future therapies for TNBC include targeted molecular strategies including poly (adenosine diphosphate ribose) polymerase (PARP) and epidermal growth factor receptor (EGFR) inhibitors and antiangiogenic agents. Further research aimed at identifying unique genetic characteristics of TNBC may allow development of other targeted molecular chemotherapy treatment options.


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