scholarly journals Synthetic Lethality of PARP Inhibitors in Combination with MYC Blockade Is Independent of BRCA Status in Triple-Negative Breast Cancer

2017 ◽  
Vol 78 (3) ◽  
pp. 742-757 ◽  
Author(s):  
Jason. P.W. Carey ◽  
Cansu Karakas ◽  
Tuyen Bui ◽  
Xian Chen ◽  
Smruthi Vijayaraghavan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Synthetic Lethality ◽  
Parp Inhibitors

scholarly journals PARP inhibitors in the treatment of metastatic breast cancer patients with germline BRCA1/2 mutations. Experience of treatment with talazoparib in clinical practice

2020 ◽  
pp. 57-61
Author(s):  
M. A. Frolova ◽  
E. V. Glazkova ◽  
M. B. Stenina
Keyword(s):  
Breast Cancer ◽  
Homologous Recombination ◽  
Base Excision Repair ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Synthetic Lethality ◽  
Excision Repair ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Base Excision

Germline BRCA1/2 mutations account for about 10% of all breast cancer. BRCA1/2 proteins are involved in homologous recombination - DNA double-strand break repair mechanism. Poly-(ADP ribose) polymerases (PARP) are required to repair DNA single-strand breaks through base excision repair. PARP inhibitors represent a modern option of treatment of metastatic HER2 negative breast cancer with germline BRCA1/2 mutations. Mechanism of action of PARP inhibitors is based on the concept of synthetic lethality under conditions of BRCA dysfunction, when both DNA repair mechanisms, homologous recombination and base excision repair, are impaired. This leads to the apoptosis of cancer cells. Currently two PARP inhibitors are registered in Russia for the treatment of BRCA-associated metastatic HER2 negative breast cancer – olaparib and talazoparib. Efficacy of PARP inhibitors olaparib and talazoparib versus standard chemotherapy has been studied in very similarly designed phase III trials OlympiAD и EMBRACA. Benefit in the progression free survival, acceptable toxicity profile and positive impact on quality of life support inclusion of PARP inhibitors in treatment schemes of metastatic BRCAassociated breast cancer. Very important is the role of PARP inhibitors in treatment of very aggressive triple negative breast cancer with limited number of effective therapy options. We represent here a clinical case of treatment of metastatic triple negative breast cancer with talazoparib in 4th line of therapy.

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 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 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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