The Impact of Platinum-Containing Chemotherapies in Advanced Triple-Negative Breast Cancer: Meta-Analytical Approach to Evaluating Its Efficacy and Safety

2021 ◽  
pp. 1-10
Author(s):  
Rui Yang ◽  
You-Yang Shi ◽  
Xiang-Hui Han ◽  
Sheng Liu
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Cochrane Library ◽  
Control Group ◽  
Chemotherapy Group ◽  
Significant Difference ◽  
The Impact

<b><i>Background:</i></b> Triple-negative breast cancer (TNBC), the most common type of breast cancer, is associated with poor patient prognosis. Platinum-containing chemotherapies are commonly used in the treatment and prevention of advanced TNBC. <b><i>Objectives and Methods:</i></b> To systematically evaluate the effectiveness and safety of platinum-containing chemotherapies in patients with advanced TNBC, we searched several databases, including PubMed, Medline, Embase, ClinicalTrials.gov, Cochrane Library, CNKI, CBM, and the Chinese Cochrane Center, to collect published randomized controlled clinical studies of platinum-containing chemotherapies for advanced TNBC before November 2020. The meta-analysis was performed using Review Manager version 5.3. To assess effectiveness and safety, dichotomous and continuous variables were assessed using odds ratio (OR) and mean difference (MD), respectively, with 95% CI. <b><i>Results:</i></b> A total of 1,222 patients with advanced TNBC were enrolled in 11 eligible trials, including 489 patients in the treatment group (platinum-containing) and 447 patients in the control group (non-platinum-containing). We also retrieved information whether a PARP inhibitor was combined with platinum-containing chemotherapy for patients with metastatic TNBC and identified 224 patients who received a PARP inhibitor combined with platinum-containing chemotherapy and 62 patients in the platinum-containing group who did not. The platinum-containing chemotherapy group had a significantly better objective response rate (OR 1.43, 95% CI 1.20–1.71, <i>p</i> &#x3c; 0.001) and longer progression-free survival (PFS; MD 1.15, 95% CI 0.03–2.28, <i>p</i> &#x3c; 0.05) than the non-platinum-containing chemotherapy group. However, there was no significant difference in overall survival (OS) of patients with advanced TNBC between the two groups (MD 2.04, 95% CI –0.83 to 4.91, <i>p</i> &#x3e; 0.05). Related adverse effects of platinum-containing chemotherapies involved gastrointestinal reaction, myelosuppression and liver function damage. Platinum-containing chemotherapies were not associated with an increased incidence of adverse side effects compared with non-platinum-containing chemotherapies, with the exception of nausea and vomiting (OR 2.22, 95% CI 1.10–4.46, <i>p</i> &#x3c; 0.05). Furthermore, the addition of the PARP inhibitor iniparib to gemcitabine and carboplatin treatment improved the rate of clinical benefit, OS and PFS. <b><i>Conclusions:</i></b> Platinum-containing chemotherapy remains a highly recommended therapeutic regimen due to greater effectiveness and tolerance for patients with advanced TNBC.

scholarly journals Precision medicine in refractory metastatic triple-negative breast cancer is enhanced by molecular subtyping and genomic profiling.

2021 ◽  
Author(s):  
James D. Klingensmith
Keyword(s):  
Breast Cancer ◽  
Confidence Interval ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Therapeutic Benefit ◽  
Percent Confidence Interval ◽  
Molecular Subtyping ◽  
Phase Ib

Triple-negative breast cancer (TNBC) is a very variable disease, and molecular subtyping may enable more precise diagnosis and treatment. Our earlier work categorized TNBCs into four subgroups, each with its own set of potential treatment targets. To assess the effectiveness of these targets, we performed the study, a phase Ib/II subtyping-based and genomic biomarker-guided umbrella study. Patients with refractory metastatic TNBC were enrolled and assigned to one of seven arms: (A) pyrotinib plus capecitabine, (B) androgen receptor inhibitor plus CDK4/6 inhibitor, (C) anti-PD-1 plus nab-paclitaxel, (D) PARP inhibitor plus nab-paclitaxel, (E) and (F) anti-VEGFR plus nab-paclitaxel, or (G The major outcome measure was the rate of objective response (ORR). We included 69 patients with resistant metastatic TNBC who had previously received a median of three lines of treatment (range, 1-8). Twenty-nine (29.0 percent, 95 percent confidence interval (CI): 18.7 percent -41.2 percent ) of the 69 intention-to-treat (ITT) patients obtained an objective response. Our findings indicated that immunotherapy (arm C) had the greatest ORR (52.6 percent, 95 percent confidence interval [CI]: 28.9 percent -75.6 percent ) in the ITT group. Arm E had a good ORR (26.1 percent, 95 percent CI: 10.2 percent -48.4 percent in the ITT group), but was associated with a higher prevalence of severe adverse events (grade 3). Somatic mutations in TOP2A and CD8 immunohistochemistry score may be able to predict immunotherapy response in patients with TNBC classified as immunomodulatory. In conclusion, the phase Ib/II study demonstrated the therapeutic benefit of subtyping-based targeted therapy for refractory metastatic TNBC.

scholarly journals Breast Cancer: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Sheeba Cantanelli, MPAS, PA-C
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Vitamin D Levels ◽  
The Impact

Sheeba Cantanelli, MPAS, PA-C, of UT Southwestern Medical Center, Simmons Comprehensive Cancer Center, discusses results from studies evaluating adjuvant therapy with a PARP inhibitor in BRCA-mutated HER2-negative metastatic breast cancer; immunotherapy in the treatment of early-stage triple-negative breast cancer; adjuvant capecitabine after neoadjuvant chemotherapy in triple-negative breast cancer; the addition of palbociclib to fulvestrant in HR-positive, HER2-negative advanced breast cancer; and the impact of vitamin D levels on outcomes. Reporting is provided by The ASCO Post.

scholarly journals Does Race Affect Outcomes in Triple Negative Breast Cancer?

2010 ◽  
Vol 4 ◽  
pp. 117822341000400 ◽  
Author(s):  
Jasgit C. Sachdev ◽  
Saira Ahmed ◽  
Muhammad M. Mirza ◽  
Aamer Farooq ◽  
Lori Kronish ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Menopausal Status ◽  
Cancer Center ◽  
Early Event ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Significant Difference ◽  
The Impact

Background There is discordance among studies assessing the impact of race on outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC treated at an urban cancer center in Memphis, TN with a predominant AA patient population. Methods Patients with Stage I-III TNBC were identified from our breast database. Event free survival (EFS) and Breast cancer specific survival (BCSS) were the primary outcome measures. Cox proportional hazards models were fitted for EFS and BCSS. Results Of the 124 patients, 71% were AA. No significant association between race and stage ( P = 0.21) or menopausal status ( P = 0.15) was observed. Median age at diagnosis was significantly lower for AA versus CA women (49.5 vs. 55 years, P = 0.024). 92% of the patients received standard neo/adjuvant chemotherapy, with no significant difference in duration and type of chemotherapy between the races. With a median follow up of 23 months, 28% of AA vs. 19% of CA women had an event ( P = 0.37). 3 year EFS and BCSS trended favorably towards CA race (77% vs. 64%, log rank P = 0.20 and 92% vs. 76%, P = 0.13 respectively) with a similar trend noted on multiple variable modeling (EFS: HR 0.62, P = 0.29; BCSS: HR 0.36, P = 0.18). AA women ≥50 years at diagnosis had a significantly worse BCSS than the CA women in that age group ( P = 0.012). Conclusion Older AA women with TNBC have a significantly worse breast cancer specific survival than their CA counterparts. Overall, there is a trend towards lower survival for AA women compared to Caucasians despite uniformity of tumor phenotype and treatment. The high early event rate, irrespective of race, underscores the need for effective therapies for women with TNBC.

A Study on the Contrast-Enhanced Ultrasound of Triple Negative Breast Cancer Tissues

2020 ◽  
Vol 10 (8) ◽  
pp. 1231-1235
Author(s):  
Huajie Zhao ◽  
Min Li ◽  
Bili Liu
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Blood Perfusion ◽  
Control Group ◽  
Observation Group ◽  
Contrast Enhanced Ultrasound ◽  
Breast Cancer Patients ◽  
Contrast Enhanced ◽  
Significant Difference

Objective: To assess contrast-enhanced ultrasound (CEUS)'s value in the diagnosis of triple negative breast cancer. Methods : 83 breast cancer patients from April 2017 to May 2018 were enrolled and assigned into observation group (triple, n = 39) and control group (non-triple, n = 44). The diagnostic examinations were performed via CEUS and the features of CEUS were analyzed. Besides, patients in observation group also received magnetic resonance imaging (MRI) and the diagnostic difference was assessed. Results: Observation group showed a significantly smaller size of focus after CEUS than control group compared to before CEUS (p < 0 05) with significant difference of focus enhancement and vascular morphology between two groups (p < 0 05). As for focus blood perfusion parameters, no differences were found regarding rise time (RT) and time to peak (TTP) between the two groups (p > 0 05). However, observation group had significantly higher peak intensity (PI) and wash-in slope (WIS) (p < 0 05). Interestingly, no difference of TNBC diagnosis was observed between CEUS and MRI (p < 0 05). Conclusion: CEUS might be beneficial for screening of triple negative breast cancer before operations and can be used to monitor the focus blood perfusion in a real-time way.

scholarly journals The Clinical Value of Chemotherapy Combined With Capecitabine in Triple-Negative Breast Cancer—A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zilin Zhang ◽  
Kai Ma ◽  
Jing Li ◽  
Yeneng Guan ◽  
Chaobo Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Meta Analysis ◽  
Safety Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Annual Conference ◽  
Hand Foot Syndrome

Purpose: Triple-negative breast cancer (TNBC) is the most dangerous subtype of breast cancer with high rates of metastasis and recurrence. The efficacy of capecitabine in chemotherapy for TNBC is still controversial. This study evaluated the efficacy and safety of capecitabine combining with standard, adjuvant or neoadjuvant chemotherapy for TNBC.Methods: We systematically searched clinical studies through PubMed, Cochrane library, Embase, Wanfang Database, China Academic Journals (CNKI), and American Society of Clinical Oncology’s (ASCO) annual conference report. Studies were assessed for design and quality by the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager to quantify the effect of capecitabine combined with standard, adjuvant or neoadjuvant chemotherapy on the disease-free survival (DFS) rate and overall survival (OS) rate of TNBC patients. Furthermore, safety analysis was performed to evaluate the adverse events.Results: Twelve randomized controlled clinical trials involving totally 4854 TNBC patients were included, of which 2,214 patients received chemotherapy as control group, and 2,278 patients received capecitabine combining with chemotherapy. The results indicated that capecitabine could significantly improve the DFS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.71–0.90, P = 0.0003] and OS (HR 0.83, 95% CI 0.74–0.93, P = 0.001). In subgroup analysis, the combination of capecitabine and cyclophosphamide exhibited a significant benefit in all outcomes (DFS HR 0.75, 95% CI 0.63–0.90, P = 0.002; OS HR 0.65, 95% CI 0.52–0.80, p &lt; 0.0001). Additionally, defferent dose of capecitabine subgroup showed same significant effect on the results. Safety analysis showed that the addition of capecitabine was associated with a much higher risk of hand-foot syndrome, diarrhea and mucositis or stomatitis.Conclusion: The results showed that adjuvant capecitabine could bring significant benefits on DFS and OS to unselected TNBC patients, the combination of capecitabine and cyclophosphamide could improve the survival rate of patients, although the addition of capecitabine could bring significant side effects such as hand foot syndrome (HFS) and diarrhea.

scholarly journals Breast – conserving Surgery in Early – Stage Triple – Negative Breast Cancer: Is There a Higher Risk of Locoregional Recurrence?

2012 ◽  
Vol 12 (1) ◽  
pp. 11-14
Author(s):  
Jelena Maksimenko ◽  
Arvids Irmejs ◽  
Genadijs Trofimovics ◽  
Edvins Miklasevics
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Locoregional Recurrence ◽  
Triple Negative ◽  
Early Stage ◽  
Statistical Significance ◽  
Group Versus ◽  
Significant Difference ◽  
The Impact ◽  
Mastectomy Group

SummaryIntroduction.Triple- negative breast cancer (TNBC) is an aggressive disease with poor prognosis and high risk of locoregional recurrence (LRR).Aim of the Study.Is to examine the impact of type of surgery on locoregional recurrence in women with early- stage invasive triplenegative breast cancer (TNBC).Materials and Methods.A total of 68 women with stage I- II (T1N0M0, T2N0M0, T1N1M0, or T2N1M0) invasive, unifocal TNBC with hitologically tumor- free surgical margins were included. Patients were stratified into two groups according to surgical treatment, breast- conserving therapy (BCT) in 36 of 68 patients versus mastectomy in 32 of 68 patients. The two common founder mutations in BRCA1 (4153delA and 5382insC) in Latvia were tested using a multiplex- specific polymerase chain reaction(PCR) assay. Clinicopathological data and survival outcomes were analyzed.Results.There were no statistically significant differences in relation to age, stage, tumor size, histological type, tumor grade and nodal status between two groups. 24 patients (77.4%) in the mastectomy group and 27(75%) patients in the BCT group received chemotherapy, these difference was not statistically significant. 10(32.2%) of 32 patients in the mastectomy group and 34(94%) of 36 patients in the BCT group received postoperative radiation (P< 0.0001). There was no statistically significant difference noted in rates of distant metastases (5 cases (16.1%) in the mastectomy group versus 4 cases (11.1%) in the BCT group; P < 0.725)). A higher proportion of patients in the BCT group experienced locoregional recurrence compared with patients in the mastectomy group (3 cases (8.3%) versus 0 case (0%), respectively), but this did not reach statistical significance (P< 0.241). It was found that the tumor histology, grade, age at presentation and BRCA1 mutation status were not significant predictors of local recurrence. There was no significant difference in 5- year breast cancer- related survival between two groups (P>0.05).Conclusions.Patients after BCT have a higher locoregional recurrence rates compared to mastectomy, but this did not reach statistical significance. According to our study data BCT is not a contraindication in the TNBC.

scholarly journals Effect of Oxaliplatin, Olaparib and LY294002 in Combination on Triple-Negative Breast Cancer Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 2056
Author(s):  
Kitti Andreidesz ◽  
Balazs Koszegi ◽  
Dominika Kovacs ◽  
Viola Bagone Vantus ◽  
Ferenc Gallyas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor ◽  
Combined Treatment ◽  
Parp Inhibition ◽  
Akt Pathway ◽  
Platinum Compound ◽  
Mcf7 Cells ◽  
Cancer Line

Triple-negative breast cancer (TNBC) has a poor prognosis as the therapy has several limitations, most importantly, treatment resistance. In this study we examined the different responses of triple-negative breast cancer line MDA-MB-231 and hormone receptor-positive breast cancer line MCF7 to a combined treatment including olaparib, a poly-(ADP ribose) polymerase (PARP) inhibitor, oxaliplatin, a third-generation platinum compound and LY294002, an Akt pathway inhibitor. We applied the drugs in a single, therapeutically relevant concentration individually and in all possible combinations, and we assessed the viability, type of cell death, reactive oxygen species production, cell-cycle phases, colony formation and invasive growth. In agreement with the literature, the MDA-MB-231 cells were more treatment resistant than the MCF7 cells. However, and in contrast with the findings of others, we detected no synergistic effect between olaparib and oxaliplatin, and we found that the Akt pathway inhibitor augmented the cytostatic properties of the platinum compound and/or prevented the cytoprotective effects of PARP inhibition. Our results suggest that, at therapeutically relevant concentrations, the cytotoxicity of the platinum compound dominated over that of the PARP inhibitor and the PI3K inhibitor, even though a regression-based model could have indicated an overall synergy at lower and/or higher concentrations.

scholarly journals Blocking Fra-1 sensitizes triple-negative breast cancer to PARP inhibitor

2021 ◽  
Author(s):  
Dandan Song ◽  
Huan He ◽  
Indranil Sinha ◽  
Linnea Hases ◽  
Feifei Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor

scholarly journals PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Predictive Value ◽  
Untreated Patient ◽  
Triple Negative ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
The Impact

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

Abstract 1066: Pre-clinical combination of a PARP inhibitor, talazoparib, and carboplatin in triple-negative breast cancer

2021 ◽  
Author(s):  
Alexia Cotte ◽  
Michèle Beniey ◽  
Takrima Haque ◽  
Nelly Béchir ◽  
Audrey Hubert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitor
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