scholarly journals Place of CDK 4/6 and PARP inhibitors in the modern treatment approach of HER2-negative breast cancer

2021 ◽  
Vol 23 (3) ◽  
pp. 470-476
Keyword(s):  
Breast Cancer ◽  
Market Access ◽  
Treatment Approach ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Efficacy Data ◽  
Therapy Strategy ◽  
Federal Districts ◽  
The Russian Federation ◽  
Virtual Platform

Three educational and discussion events with 35 key specialists from federal and regional cancer centers representing 7 federal districts were organized by Pfizer with the support of TS Oncology. The events were organized on the basis of the "OncoForum" platform (virtual platform developed and operated by TS Oncology). Experts shared their opinion on CDK4/6 inhibitors and PARP inhibitors place in the optimal therapy strategy for patients with HR+/HER2- metastatic breast cancer (mBC) and BRCA-associated HER2- mBC in Russia. This review presents results of the discussions on practical aspects of defining the optimal profiles of patients with HR+/HER2- mBC and BRCA-associated HER2- mBC for using CDK4/6 inhibitors and PARP inhibitors, evaluating the efficacy data and toxicity profiles for each of the CDK4/6 inhibitors and PARP inhibitors, as well as market access specifities for CDK4/6 inhibitors to patients with HR+/HER2- mBC and PARP inhibitors to patients with gBRCA-associated HER2- mBC in different regions of the Russian Federation.

scholarly journals Role and place of PARP inhibitors in the modern treatment algorithm of BRCA-associated HER2-negative metastatic breast cancer. Results of the educational and discussion events based on the “OncoForum” platform

2021 ◽  
Vol 23 (1) ◽  
pp. 45-47
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Molecular Genetic ◽  
Treatment Algorithm ◽  
Genetic Research ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Current State ◽  
Federal Districts ◽  
Virtual Platform

In 2020, within the framework of the educational project Talisman on BRCA-associated HER2-negative metastatic breast cancer (mBC), Pfizer with the support of TS Oncology held 4 educational and discussion events based on the OncoForum platform (virtual-platform developed and operated by TS Oncology). 44 key specialists from federal and regional cancer centers representing 7 federal districts took part in these events and shared their opinion on the current state of availability of molecular genetic research for germline mutations in BRCA genes and treatment approaches of BRCA-associated HER2-negative mBC in Russia. The results of these interactive discussions are represented in the current overview.

scholarly journals Practice-Changing Interventions in the Systemic Management of Breast Cancer

2020 ◽  
Vol 18 (7.5) ◽  
pp. 941-944
Author(s):  
William J. Gradishar
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Subtype ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Targeted Agents ◽  
Her2 Positive ◽  
Nccn Guidelines ◽  
Estrogen Receptor Positive ◽  
Treatment Paradigm

Systemic treatment for metastatic breast cancer now incorporates many targeted agents and a plethora of combinations specific to the breast cancer subtype. New to the treatment paradigm are fam-trastuzumab deruxtecan-nxki, and tucatinib for HER2-positive disease; the PI3K inhibitor alpelisib in combination with fulvestrant for estrogen receptor–positive and PIK3CA-mutated tumors; PARP inhibitors for patients with germline BRCA1/2 mutations; and the anti–PD-L1 agent atezolizumab in combination with albumin-bound paclitaxel for triple-negative disease with PD-L1 mutations in tumors. In addition, for estrogen receptor–positive disease, the role of CDK4/6 inhibitors increased substantially during the past year, as overall survival results have emerged. These targeted agents are greatly improving patient outcomes, and thus have all been incorporated into the NCCN Guidelines for Breast Cancer.

scholarly journals Rucaparib in patients presenting a metastatic breast cancer with Homologous Recombination Deficiency, without germline BRCA1/2 mutation

2020 ◽  
Author(s):  
Anne Patsouris ◽  
M'boyba Khadija DIOP ◽  
Olivier Tredan ◽  
Daniel Nenciu ◽  
Anthony Goncalves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Homologous Recombination ◽  
Statistical Significance ◽  
Objective Response ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Small Subset ◽  
Durable Response ◽  
Homologous Recombination Deficiency

Abstract Breast cancer may present genomic alterations leading to homologous recombination deficiency. PARP inhibitors have proved their efficacy in patients with HER2-negative metastatic breast cancer (mBC) harboring germline (g) BRCA1/2 mutations. We conducted the phase 2 RUBY trial to assess the efficacy of rucaparib in HER2-negative mBC with high genomic loss of heterozygosity (LOH) score or somatic, without gBRCA1/2 mutation. 220 of 711 patients with mBC screened for LOH presented high LOH score which was associated with a higher likelihood of death (HR = 1.39, 95% CI: 1.11-1.75, p = 0.005). The primary objective was not reached with a clinical benefit rate (objective response or SD>16 weeks) of 13.5%. Two LOH-high patients, without somatic BRCA1/2 mutation, presented a complete and durable response (14 and 32 months). HRDetect tended to be associated with response to rucaparib, whithout reaching statistical significance (median HRDetect responders versus non responders: 0.465 versus, 0.040, p = 0.2135). Our data suggests that a small subset of patients with high LOH score could derive benefit from PARP inhibitors.

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 Update Breast Cancer 2020 Part 2 – Advanced Breast Cancer: New Treatments and Implementation of Therapies with Companion Diagnostics

2020 ◽  
Vol 80 (04) ◽  
pp. 391-398
Author(s):  
Diana Lüftner ◽  
Andreas Schneeweiss ◽  
Andreas D. Hartkopf ◽  
Volkmar Müller ◽  
Achim Wöckel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Targeted Therapy ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Companion Diagnostics ◽  
Molecular Tests ◽  
New Treatments ◽  
First Time

AbstractFor patients with locally advanced or metastatic breast cancer, new and effective therapies such as CDK4/6 inhibitors, PARP inhibitors and a PD-L1 inhibitor have been introduced in recent years. This review presents an update on the available studies with their data. In addition, two innovative anti-HER2 therapies are presented (trastuzumab-deruxtecan and tucatinib) for which the results from new studies have been reported. Molecular tests offer the possibility of defining patient populations or also monitoring courses of therapy. This can help identify patients with specific characteristics in order to provide them with individually targeted therapy within the framework of studies. In a large study, the benefit of such a biomarker study was able to be described for the first time.

scholarly journals Update Breast Cancer 2019 Part 4 – Diagnostic and Therapeutic Challenges of New, Personalised Therapies for Patients with Early Breast Cancer

2019 ◽  
Vol 79 (10) ◽  
pp. 1079-1089 ◽  
Author(s):  
Florian Schütz ◽  
Peter A. Fasching ◽  
Manfred Welslau ◽  
Andreas D. Hartkopf ◽  
Achim Wöckel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Homologous Recombination ◽  
Early Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Further Development

AbstractThe further development of therapies for women with early breast cancer is progressing far more slowly than in the case of patients with advanced breast cancer and is additionally delayed compared to developments in metastatic breast cancer. Nonetheless, significant advancements have been able to be recorded recently. This review summarises the latest developments in view of the most recent publications and professional conferences. For hormone-receptor-positive patients, new aspects for the duration of antihormone therapy and with regard to the benefits of multigene tests have been published. In the case of HER2-positive patients, the value of post-neoadjuvant therapy and de-escalation of the therapy is discussed. In patients with triple-negative breast cancer, there is a question of whether the knowledge of the biological background of a homologous recombination deficiency (HRD) helps develop new therapies for this subtype. In particular the “use” of a BRCA1/2 mutation or the biological characteristic HRD as a potential motive for therapy plays a role here in specifying the significance of platinum therapy and therapy with PARP inhibitors.

PARP inhibitors (PARPi) for the treatment of BRCA-mutated HER2-negative (HER2-) metastatic breast cancer (MBC) patients: A systematic review and meta-analysis.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13098-e13098 ◽  
Author(s):  
Francesca Poggio ◽  
Marco Bruzzone ◽  
Marcello Ceppi ◽  
Benedetta Conte ◽  
Samuel Martel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Metastatic Breast Cancer ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Parp Inhibitors

Measurement of gamma-H2AX in circulating tumor cells (CTC) from patients receiving ABT-888 (veliparib) in combination with carboplatin on a phase I dose-escalation study (OSU-10080/NCI8609).

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 58-58
Author(s):  
A. Garcia-Villa
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Immunocytochemical Staining ◽  
Dose Escalation Study ◽  
Non Invasive

58 Background: Non-invasive methods to accurately measure DNA damage induced by PARP inhibitors in the tumors are crucial in identifying the optimal biological dose and schedule of these novel agents. With the use of an antibody that targets the histone H2AX, which becomes phosphorylated on serine residue 139 (γ-H2AX), it is possible to measure DNA DSB in the cell. But repeated biopsy in patients with metastatic breast cancer is not feasible. We propose here to quantify γ-H2AX in CTCs as a measurement of DNA damage in the tumor in patients receiving veliparib (ABT-888), an oral PARP inhibitor and carboplatin on a phase I study. Methods: CTCs were isolated in 10 mL of peripheral blood using negative selection with immunomagnetic tagging and removal of CD45 positive cells at 3 time points. Immunocytochemical staining for nucleus (DAPI), pan-cytokeratin CD45, and γ-H2AX was completed on available samples. Double staining for nucleus and cytokeratin with high nucleus to cytoplasm ratio defined a CTC. The γ-H2AX foci present in the nucleus of the CTCs will be counted by immunocytochemistry (ICC) analysis. Results: We negatively enriched blood sample from enrolled patients with metastatic breast cancer (n=6). CTCs were observed in all samples (55CTCs/mL of blood - 2000CTCs/mL of blood). Thus far 3 out of 6 patient samples have been analyzed. The number of CTCs per mL of blood after enrichment at baseline has a mean of 293, a median of 140 and a range of (684-140) At time point 1 the mean is 1071.33, the median is 1151 and the range is (1151-63). ICC analysis on the CTCs demonstrated the presence of γ-H2AX positive cells. Conclusions: Our novel negative depletion method for isolating CTCs allows for separation of a wider range of CTCs, since it does not assume presence of epithelial markers before separation. This leads to improved yield and purity allowing better ICC detection of various markers directly on CTCs. Development and validation of the above methodology to determine γ-H2AX foci in CTCs will help in identifying a novel, non-invasive biomarker that can be used to assess the effect of DNA damaging agents during therapy.

Sign in / Sign up

Export Citation Format

Share Document