scholarly journals The overview of modern approaches in treatment of triple negative breast cancer

2020 ◽  
Vol 7 (1) ◽  
pp. 55-65
Author(s):  
A. A. Kharitonova ◽  
I. A. Smirnova ◽  
M. V. Kiseleva
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitors ◽  
Morphological Response ◽  
Chemotherapy Drugs ◽  
Treatment Regimens ◽  
Dose Dense ◽  
Platinum Preparations ◽  
Aggressive Subtype

By far the most aggressive subtype of breast cancer is triple negative cancer. The purpose of this review is to analyze current ideas about the pathogenesis, clinical characteristics of different subtypes of triple negative breast cancer, the nature of its metastasis, mechanisms of chemoresistance. The review presents the results of modern regimens of drug therapy of triple negative breast cancer according to the publications of domestic and foreign oncologists. On the basis of various clinical studies, the effectiveness of the use of anthracyclines, taxanes in the dose-dense regime, platinum preparations and other chemotherapy drugs for the treatment of triple-negative cancer has been shown. The presented treatment regimens allow to achieve a complete morphological response in 85% of patients, to increase the rates of relapse-free and overall survival, comparable with other subtypes of breast cancer. The review highlights the possibilities of modern targeted drugs-PARP inhibitors, chk1 inhibitors UCN‑01, immunotherapy possibilities for the treatment of this aggressive subtype of breast cancer.

scholarly journals Modulation of Early Mitotic Inhibitor 1 (EMI1) depletion on the sensitivity of PARP inhibitors in BRCA1 mutated triple-negative breast cancer cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0235025
Author(s):  
Dina Moustafa ◽  
Maha R. Abd Elwahed ◽  
Hanaa H. Elsaid ◽  
Jeffrey D. Parvin
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitors ◽  
Cytotoxic Drugs ◽  
Breast Cancers ◽  
Cell Viability Assay ◽  
Rad51 Protein ◽  
Chemotherapy Drugs ◽  
Chk1 Inhibitor

Triple negative breast cancer (TNBC) represents approximately 10–15% of all breast cancers and has a poor outcome as it lacks a receptor target for therapy, and TNBC is frequently associated with a germline mutation of BRCA1. Poly (ADP-ribose) polymerase inhibitor (PARPi) drugs have demonstrated some effectiveness in treating BRCA1 or BRCA2 mutated breast and ovarian cancers but resistance to PARPi is common. Published results found that resistance to Olaparib, a PARPi, can be due to downregulation of EMI1 and the consequent upregulation of the RAD51 recombinase. Using a tissue culture-based cell viability assay, we extended those observations to another PARPi and to other chemotherapy drugs that affect DNA repair or the cell cycle. As we expected, EMI1 downregulation resulted in resistance to another PARPi drug, Talazoparib. EMI1 downregulation also led to resistance to other cytotoxic drugs, Cisplatin and CHK1 inhibitor. Notably, increasing the RAD51 protein expression only recapitulated some, but not all, of the effects of EMI1 depletion in conferring to the cell resistance to different PARPi and the other cytotoxic drugs. These results suggest that the downstream effects of EMI1 downregulation that contribute to PARPi resistance are increasing the concentration of RAD51 protein in the cell and blocking mitotic entry. We found that combining CHK1 inhibitor with olaparib results in restoration of sensitivity even when EMI1 expression is downregulated. This combination therapy may be a means to overcome the PARPi resistance in BRCA1-deficient TNBC cells.

scholarly journals A review of current progress in triple-negative breast cancer therapy

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1143-1149
Author(s):  
Meiying Shen ◽  
Huawen Pan ◽  
Yuxia Chen ◽  
Yu Hang Xu ◽  
Weixiong Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Brca Mutation ◽  
Complete Response ◽  
Parp Inhibitors ◽  
The Past ◽  
Germline Brca Mutation ◽  
Aggressive Subtype

AbstractTriple-negative breast cancer (TNBC) is a particularly aggressive subtype known for its extremely high drug resistance, progression, poor prognosis, and lack of clear therapeutic targets. Researchers are aiming to advance TNBC treatment worldwide. In the past 2–3 years, more positive results have emerged in the clinical research on TNBC treatment. Based on the results, several impressive drugs have been approved to benefit patients with TNBC, including the PARP inhibitors olaparib and talazoparib for germline BRCA mutation-associated breast cancer (gBRCAm-BC) and immunotherapy using the checkpoint inhibitor atezolizumab in combination with nab-paclitaxel for programmed cell death-ligand 1-positive (PD-L1+) advanced TNBC. Although neoadjuvant therapy has focused on combinations of systemic agents to optimize pathologically complete response, metastatic TNBC still has a poor prognosis. Innovative multidrug combination systemic therapies based on neoadjuvants and adjuvants have led to significant improvements in outcomes, particularly over the past decade.

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 Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

Nano Research ◽  
2019 ◽  
Vol 12 (4) ◽  
pp. 855-861 ◽  
Author(s):  
Chengxiang Zhang ◽  
Xinfu Zhang ◽  
Weiyu Zhao ◽  
Chunxi Zeng ◽  
Wenqing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Chemotherapy Drugs ◽  
Tumor Suppressor Proteins

scholarly journals Translating the role of PARP inhibitors in triple-negative breast cancer

Oncoscience ◽  
2019 ◽  
Vol 6 (1-2) ◽  
pp. 287-288 ◽  
Author(s):  
Michèle Beniey ◽  
Takrima Haque ◽  
Saima Hassan
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitors

scholarly journals PARP Inhibitor Olaparib Use in a BRCA1-Positive Patient With Metastatic Triple-Negative Breast Cancer, Without the Initial Use of Platinum-Based Chemotherapy, Showing Significant Rapid Near Resolution of Large Liver Metastasis While Patient Experienced Gout-Like Symptoms

2019 ◽  
Vol 7 ◽  
pp. 232470961986498 ◽  
Author(s):  
Trevanne Matthews Hew ◽  
Lara Zuberi
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Management Options ◽  
Federal Drug Administration ◽  
Platinum Based Chemotherapy ◽  
Metastatic Setting

Triple-negative breast cancer (TNBC) accounts for 20% of breast cancers diagnosed worldwide. This subtype of breast cancer tends to behave more aggressively, and unlike other breast cancer subtypes, there are no standard targeted treatments for most patients. However, up to 20% of patients with TNBC harbor a breast cancer gene (BRCA) mutation, particularly in BRCA1. For patients who carry this gene mutation, this opens the door for new management options by the use of newer agents such as polyadenosine diphosphate-ribose polymerase (PARP) inhibitors in the metastatic setting. Given that this is uncommon and that PARP inhibitors have only recently received Federal Drug Administration approval, the experience with these drugs is relatively new. In this article, we present a case of a patient treated in this setting with olaparib who developed an unanticipated side effect as a result of the high efficacy of the drug.

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