scholarly journals Opportunities for metastatic triple negative breast cancer therapy

2021 ◽  
Vol 23 (1) ◽  
pp. 78-81
Author(s):  
Inna P. Ganshina ◽  
Olga O. Gordeeva ◽  
Mariam S. Manukyan
Keyword(s):  
Breast Cancer ◽  
Russian Federation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Parp Inhibitors ◽  
Treatment Results ◽  
The Russian Federation ◽  
Biological Heterogeneity ◽  
New Treatment

Metastatic triple negative breast cancer (mTNBC) is a difficult task for the chemotherapist in view of the disease aggressiveness, biological heterogeneity of the tumor, as well as the limit of therapy options. The approved modern drugs, such as immunotherapy and PARP inhibitors, have improved the treatment results in women with mTNBC. However, not all women are the candidates for this kind of therapy due to the lack of suitable points of application. In this context, high hopes are placed on the new treatment options currently being studied in clinical trials. The review summarizes data on advanced drugs that have demonstrated their efficacy in this multiplex group of women, but not yet registered at the territory of the Russian Federation Russian Federation, and will allow us to form an idea of the future algorithm of treatment of women with mTNBC.

scholarly journals Identifying Biomarkers to Pair with Targeting Treatments within Triple Negative Breast Cancer for Improved Patient Stratification

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1864 ◽  
Author(s):  
Holly Tovey ◽  
Maggie Chon U. Cheang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
High Throughput Sequencing ◽  
Triple Negative ◽  
Treatment Options ◽  
Unmet Need ◽  
Growth Factor Receptor ◽  
Parp Inhibitors ◽  
Genetic Features ◽  
The Uk

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.

scholarly journals A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S32783 ◽  
Author(s):  
Simon B. Zeichner ◽  
Hiromi Terawaki ◽  
Keerthi Gogineni
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Symptomatic Disease ◽  
Metastatic Setting ◽  
Epidermal Growth ◽  
New Treatment

Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.

scholarly journals Treatment options in early triple-negative breast cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 346-348
Author(s):  
Christoph Suppan ◽  
Marija Balic
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
San Antonio ◽  
Treatment Options ◽  
Circulating Tumor Dna ◽  
Predictive Tool ◽  
New Treatment

Summary With a main focus on the early stage triple-negative breast cancer (TNBC), new data on immunotherapy in combination with chemotherapy, the role of capecitabine, the potential of circulating tumor DNA as a predictive tool in the postneoadjuvant setting and new treatment approaches were presented and discussed at the San Antonio Breast Cancer Symposium (SABCS) 2019.

scholarly journals Pin1 plays a key role in the response to treatment and clinical outcome in triple negative breast cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592090604 ◽  
Author(s):  
Catherine Knowlson ◽  
Paula Haddock ◽  
Victoria Bingham ◽  
Stephen McQuaid ◽  
Paul B. Mullan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Standard Of Care ◽  
Parp Inhibitors ◽  
Response To Treatment ◽  
Increased Sensitivity

Background: Triple negative breast cancer (TNBC) is the subset of breast cancer associated with the poorest outcome, and currently lacks targeted treatments. Standard of care (SoC) chemotherapy often consists of DNA damaging chemotherapies ± taxanes, with a range of responses observed. However, we currently lack biomarkers to predict this response and lack alternate treatment options. Methods: Pin1 expression was modulated in vitro and proliferation and treatment response was studied. Pin1 expression was analysed in patient samples and correlated with clinical outcome. Results: In this study, we have shown that the prolyl isomerase, Pin1, which is highly expressed in TNBC, plays a key role in pathogenesis of the disease. Knockdown of Pin1 in TNBC resulted in cell death while the opposite is seen in normal cells. We revealed for the first time that loss of Pin1 leads to increased sensitivity to Taxol but only in the absence of functional BRCA1. Conversely, loss of Pin1 results in decreased sensitivity to DNA-damaging agents independent of BRCA1 status. Analysis of Pin1 gene or IHC-based expression in over 200 TNBC patient samples revealed a novel role for Pin1 as a TNBC-specific biomarker, with high expression associated with improved outcome in the context of SoC chemotherapy. Preliminary data indicated this may be extended to other treatment options (e.g. Cisplatin/Parp Inhibitors) that are gaining traction for the treatment of TNBC. Conclusions: This study highlights the important role played by Pin1 in TNBC and highlights the context-dependent functions in modulating cell growth and response to treatment.

scholarly journals Novel therapeutic strategies for patients with metastatic triple-negative breast cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 60-65
Author(s):  
Inna P. Ganshina ◽  
Olga O. Gordeeva ◽  
Mariam Sh. Manukian
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Russian Federation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Clinical Trial Data ◽  
Distant Metastases ◽  
Resistance Mechanisms ◽  
The Russian Federation

Triple-negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer. In the presence of distant metastases, the median overall survival does not exceed 14 months. TNBC is an extremely heterogeneous group of tumors, it includes both tumors extremely sensitive to chemotherapy and tumors that require targeted or immunotherapy for the best treatment outcomes. Such subtype features make it difficult to develop a single treatment strategy for all patients. Current perceptions of resistance mechanisms and molecular drivers progression have increased therapeutic opportunities for metastatic TNBC (mTNBC). For example, in the last few years, checkpoint inhibitors and PARP inhibitors have entered into clinical practice in the Russian Federation. This review presents clinical trial data, as well as an algorithm for choosing therapy for patients with TNBC, based on the results of recent clinical studies. The review focuses mainly on drugs registered at the territory of the Russian Federation, that allows to apply these options in everyday clinical practice. Promising directions therapy of mTNBC not registered at the territory of the Russian Federation yet will be showed in a separate review in the next issue in the Journal of Modern Oncology.

scholarly journals New Treatment Options in ER-Positive, HER2-Positive and Triple-Negative Breast Cancer

Breast Care ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. 2-2
Author(s):  
Günther Steger ◽  
Richard Bell ◽  
David Cameron ◽  
Rebecca A. Dent ◽  
Christian Jackisch
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Her2 Positive ◽  
Er Positive ◽  
New Treatment

scholarly journals Optimizing cisplatin delivery to triple-negative breast cancer through novel EGFR aptamer-conjugated polymeric nanovectors

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Lisa Agnello ◽  
Silvia Tortorella ◽  
Annachiara d’Argenio ◽  
Clarissa Carbone ◽  
Simona Camorani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Ex Vivo ◽  
Treatment Options ◽  
Negative Control ◽  
Therapeutic Effects ◽  
Metastatic Setting

Abstract Background Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic compound in neoadjuvant approaches and in the metastatic setting, but its use is limited by scarce bioavailability, severe systemic side effects and drug resistance. Novel site-directed aptamer-based nanotherapeutics have the potential to overcome obstacles of chemotherapy. In this study we investigated the tumor targeting and the anti-tumorigenic effectiveness of novel cisplatin-loaded and aptamer-decorated nanosystems in TNBC. Methods Nanotechnological procedures were applied to entrap cisplatin at high efficacy into polymeric nanoparticles (PNPs) that were conjugated on their surface with the epidermal growth factor receptor (EGFR) selective and cell-internalizing CL4 aptamer to improve targeted therapy. Internalization into TNBC MDA-MB-231 and BT-549 cells of aptamer-decorated PNPs, loaded with BODIPY505-515, was monitored by confocal microscopy using EGFR-depleted cells as negative control. Tumor targeting and biodistribution was evaluated by fluorescence reflectance imaging upon intravenously injection of Cyanine7-labeled nanovectors in nude mice bearing subcutaneous MDA-MB-231 tumors. Cytotoxicity of cisplatin-loaded PNPs toward TNBC cells was evaluated by MTT assay and the antitumor effect was assessed by tumor growth experiments in vivo and ex vivo analyses. Results We demonstrate specific, high and rapid uptake into EGFR-positive TNBC cells of CL4-conjugated fluorescent PNPs which, when loaded with cisplatin, resulted considerably more cytotoxic than the free drug and nanovectors either unconjugated or conjugated with a scrambled aptamer. Importantly, animal studies showed that the CL4-equipped PNPs achieve significantly higher tumor targeting efficiency and enhanced therapeutic effects, without any signs of systemic toxicity, compared with free cisplatin and untargeted PNPs. Conclusions Our study proposes novel and safe drug-loaded targeted nanosystems for EGFR-positive TNBC with excellent potential for the application in cancer diagnosis and therapy.

scholarly journals Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3357
Author(s):  
Hongmei Zheng ◽  
Sumit Siddharth ◽  
Sheetal Parida ◽  
Xinhong Wu ◽  
Dipali Sharma
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Combined Treatment ◽  
High Mobility ◽  
Sphingosine 1 Phosphate ◽  
Molecular Patterns

Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

scholarly journals Triple Negative Breast Cancer: A review of common therapeutic Targets and Current Treatment options.

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Daud Akhtar ◽  
Ahsen Chaudhry
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Side Effects ◽  
Triple Negative Breast Cancer ◽  
Cancer Du Sein ◽  
Triple Negative ◽  
Treatment Options ◽  
Cell Signalling ◽  
Effets Secondaires ◽  
Breast Cancer Chemotherapy

Triple negative breast cancer (TNBC) is a subtype of breast cancer which lacks ER, PR, and HER2 expression. It is characterized by poor prognosis and resistance to standard treatment forms for breast cancer. Chemotherapy is still currently the core neo-adjuvant treatment option for patients with TNBC, although it has mixed levels of efficacy on overall survival and many serious side effects. Platinum- based therapies have been used to treat TNBC in conjunction with chemotherapy, but they are not a widely effective treatment due to the heterogeneity of TNBC. For this reason, other novel approaches, particularly those which target molecular components involved in TNBC pathogenesis, are being investigated. Angiogenesis inhibitors, which include monoclonal antibodies or small molecules that inhibit VEGF, have been shown to improve progression-free survival, but have not demonstrated an impact on overall survival. PARP enzyme inhibitors, when combined with chemotherapy and carboplatin for the treatment of TNBC, have demonstrated a significant reduction in risk progression and mortality. However, the majority of PARP inhibitors are still in trials and their effectiveness in clini- cal settings has yet to be determined. Additional proposed targets for directed therapy against TNBC include cell signalling pathways involving EGFR or PI3K. Overall, issues such as treatment resistance and side effects are important challenges that must be overcome in order to enable improvements in patient prognosis and clinical impact. RÉSUMÉ Le cancer du sein triple négatif (CSTN) est un sous-type de cancer du sein auquel il manque les récepteurs d’œstrogènes (ER), les récepteurs de progestérone (PR) et l’expression de HER2. Il est caractérisé par un pronostic défavorable et une résistance aux traite- ments standards du cancer du sein. À l’heure actuelle, la chimiothérapie est encore l’option principale de traitement néoadjuvant pour les patients ayant le CSTN, bien qu’elle ait des niveaux variés d’efficacité sur la survie globale, ainsi que de nombreux effets secondaires sérieux. Les thérapies à base de platine ont été utilisées pour traiter le CSTN en conjonction avec la chimiothérapie, mais elles ne sont pas très efficaces étant donné l’hétérogénéité du CSTN. En raison de cela, d’autres approches novatrices, particulièrement celles qui ciblent les composantes moléculaires impliquées dans la pathogenèse du CSTN, font actuellement l’objet d’enquêtes. Les inhibiteurs de l’angiogenèse, dont les anticorps monoclonaux ou les petites molécules inhibant le VEGF, ont démontré la capacité d’améliorer la survie sans progression de la maladie, mais n’ont pas démontré d’impact sur la survie globale. Les inhibiteurs d’enzymes PARP, lorsque combinés avec la chimiothérapie et le carboplatine pour le traitement du CSTN, ont démontré une réduction significative du risque de progression et de la mortalité. Toutefois, la majorité des inhibiteurs PARP subissent encore des essais et leur efficacité clinique reste à être déterminée. D’autres cibles suggérées pour la thérapie dirigée contre le CSTN incluent les voies de signalisation impliquant le EGFR ou le PI3K. Dans l’ensemble, des problèmes tels la résistance au traitement et les effets secondaires sont des défis importants qui doivent être surmontés afin de permettre des améliorations au niveau du pronostic du patient et de l’impact clinique. 

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