The predictive and prognostic role of phosphatase phosphoinositol-3 (PI3) kinase (PIK3CA) mutation in HER2-positive breast cancer receiving HER2-targeted therapy: a meta-analysis

2015 ◽  
Vol 152 (3) ◽  
pp. 463-476 ◽  
Author(s):  
Ezzeldin M. Ibrahim ◽  
Ghieth A. Kazkaz ◽  
Mubarak M. Al-Mansour ◽  
Meteb E. Al-Foheidi
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Meta Analysis ◽  
Pik3ca Mutation ◽  
Pi3 Kinase ◽  
Prognostic Role ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals 34. TARGETED THERAPY FOR HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
Anders Erickson ◽  
Farinaz Ghodrati ◽  
Sunit Das
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Meta Analyses ◽  
Positive Breast Cancer

Abstract INTRO One in three women with HER2-positive breast cancer will develop brain metastases, or intracranial metastatic disease (IMD). Historically, treatment of IMD has been confined to surgery and radiotherapy, with a limited role for chemotherapy. However, recent interest has burgeoned in a role for targeted therapy for treatment of IMD. The lack of high-level evidence, such as meta-analyses, regarding the role of targeted therapy in the management of IMD has prevented its inclusion in guidelines directing treatment. We performed a systematic review and meta-analysis to clarify the role of targeted therapy for IMD in women with HER2-positive breast cancer. METHODS Following PRISMA guidelines, a search of MEDLINE, CENTRAL, EMBASE, Google Scholar, and grey literature sources was conducted by two independent reviewers. Controlled trials and cohort studies that reported survival, safety, or response outcomes for patients receiving HER2-targeted therapy following IMD diagnosis were included. Meta-analyses using a random-effects model were conducted for OS and PFS. RESULTS 111 studies reporting on 8226 patients were included. Primary analysis of only RCTs found that HER2-targeted therapy was associated with improved OS (HR 0.63; 95% CI, 0.46–0.86; n = 392) but not PFS (HR 0.75; 95% CI, 0.30–1.85; n = 392) following IMD diagnosis. Secondary analysis combining RCTs and comparative observational studies found that HER2-targeted therapy was associated with improved OS (HR 0.42; 95% CI, 0.35–0.51; n = 2756) but not PFS (HR 0.58; 95% CI, 0.27–1.21; n = 460) following IMD diagnosis. Full analysis will be conducted for all 111 studies for pre-specified outcomes including intracranial PFS. CONCLUSION These findings support a potential role for HER2-targeted therapy in the management of IMD from HER2-positive breast cancer. Final analysis will synthesize current evidence for outcomes of intracranial response, survival, and safety.

scholarly journals HER2-targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: a systematic review and meta-analysis

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Anders W Erickson ◽  
Farinaz Ghodrati ◽  
Steven Habbous ◽  
Katarzyna J Jerzak ◽  
Arjun Sahgal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Metastatic Disease ◽  
Response Rate ◽  
Meta Analysis ◽  
Adverse Event Rate ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Intracranial Metastatic Disease ◽  
Positive Breast Cancer

Abstract Background Intracranial metastatic disease (IMD) is a serious and known complication of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The role of targeted therapy for patients with HER2-positive breast cancer and IMD remains unclear. In this study, we sought to evaluate the effect of HER2-targeted therapy on IMD from HER2-positive breast cancer. Methods We searched MEDLINE, EMBASE, CENTRAL, and gray literature sources for interventional and observational studies reporting survival, response, and safety outcomes for patients with IMD receiving HER2-targeted therapy. We pooled outcomes through meta-analysis and examined confounder effects through forest plot stratification and meta-regression. Evidence quality was evaluated using GRADE (PROSPERO CRD42020161209). Results A total of 97 studies (37 interventional and 60 observational) were included. HER2-targeted therapy was associated with prolonged overall survival (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.39–0.56) without significantly prolonged progression-free survival (HR 0.52; 95% CI, 0.27–1.02) versus non-targeted therapy; the intracranial objective response rate was 19% (95% CI, 12–27%), intracranial disease control rate 62% (95% CI, 55–69%), intracranial complete response rate 0% (95% CI, 0–0.01%), and grade 3+ adverse event rate 26% (95% CI, 11–45%). Risk of bias was high in 40% (39/97) of studies. Conclusion These findings support a potential role for systemic HER2-targeted therapy in the treatment of patients with IMD from HER2-positive metastatic breast cancer.

scholarly journals Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3540
Author(s):  
Hamid Maadi ◽  
Mohammad Hasan Soheilifar ◽  
Won-Shik Choi ◽  
Abdolvahab Moshtaghian ◽  
Zhixiang Wang
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Cancer Patients ◽  
Mechanism Of Action ◽  
Mechanisms Of Action ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Insight Into ◽  
Positive Breast Cancer

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened a new avenue to treat patients with HER2-positive breast cancer and other types of cancer, some patients are not responsive or become resistant to this treatment. So far, several mechanisms have been suggested for the mode of action of trastuzumab; however, the findings regarding these mechanisms are controversial. In this review, we aimed to provide a detailed insight into the various mechanisms of action of trastuzumab.

scholarly journals Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials

2021 ◽  
Vol 22 (8) ◽  
pp. 1139-1150
Author(s):  
Rosie Bradley ◽  
Jeremy Braybrooke ◽  
Richard Gray ◽  
Robert Hills ◽  
Zulian Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Meta Analysis ◽  
Randomised Trials ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Linc01638 Promotes Tumorigenesis in HER2+ Breast Cancer

2018 ◽  
Vol 19 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Peng Liu ◽  
Hailin Tang ◽  
Jiali Wu ◽  
Xingsheng Qiu ◽  
Yanan Kong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Mouse Xenograft ◽  
Her2 Positive Breast Cancer ◽  
Mouse Xenograft Model ◽  
Positive Breast Cancer

Background: Long non-coding RNAs play crucial roles in various biological activities and diseases. The role of long intergenic non-coding RNA01638 (linc01638) in breast cancer, especially in HER2-positive breast cancer, remains largely unknown. Objective: To investigate the effect of linc01638 on tumorigenesis in HER2-positive breast cancer. </P><P> Methods: We first used qRT-PCR to detect linc01638 expression in HER2-positive breast cancer cells and tissues. Then we analyzed the effects of linc01638 expression in HER2-positive breast cancer cells through cell apoptosis assay, cell proliferation assay, colony formation assay, and cell invasion assay. We conducted mouse xenograft model to further confirm the role of linc01638 in HER2-positive breast cancer. Moreover, we used Western blot and IHC analysis to access the effect of linc01638 on DNMTs, BRCA1 and PTEN expressions in transplanted tumors. Results: Linc01638 was found to be remarkably overexpressed in HER2-positive breast cancer cells and tissues. Suppression of linc01638 enhanced cell apoptosis, as well as inhibited the growth and invasiveness of HER2-positive breast cancer cells in vitro and tumor progression and metastasis in vivo. Furthermore, inhibition of linc01638 by shRNA attenuated expression of DNMT1, DNMT3a, and DNMT3b, and promoted expression of BRCA1 and PTEN in HER2-positive breast cancer cells and mouse xenograft models. Linc01638 might be a promising biomarker and therapeutic target for treatment of HER2-positive breast cancer.

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