Recent advances in genetics and genomics have revealed new pathways that are aberrantly activated in many breast cancers. Chief among these genetic changes are somatic mutations and/or gains and losses of key genes within the phosphoinositide 3-kinase (PI3K) pathway. Since breast cancer cell growth and progression is often dependent upon activation of the PI3K pathway, there has been intense research interest in finding therapeutic agents that can selectively inhibit one or more constituents of this signaling cascade. Here we review key molecules involved with aberrant PI3K pathway activation in breast cancers and current efforts to target these components for therapeutic gain.

Targeting the PI3K/Akt/mTOR Pathway for Breast Cancer Therapy

Gene variants are dependable and sensitive biomarkers for target-specific therapies in breast cancer (BC). However, detection of mutations within tissues has many limitations. Plasma circulating free DNA (cfDNA) has been reported in many studies as an alternative tool for detection of mutations. But the diagnostic accuracy of cfDNA for most mutations in BC needs to be reviewed. This study was designed to perform comparative assessment of the diagnostic performance of cfDNA and DNA extracted from tissues for detection of single nucleotide variants (SNV) and copy number variants (CNV). True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted from each selected study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Subgroup analysis and single study omitted analysis were performed to quantify and explain the study heterogeneity. Twenty eligible studies that involved 1055 cases were included in this meta-analysis. SNV studies in early breast cancer (EBC) subgroup are not suitable for meta-analysis owing to high heterogeneity. However, in advanced breast cancer (ABC) subgroup, the pooled sensitivity and specificity of detection of SNVs were 0.78 (0.71–0.84) and 0.92 (0.87–0.95), respectively. The summary receiver operative curve (SROC) exhibited an area under the curve (AUC) of 0.91(0.88–0.93). The pooled results of studies involving subgroups of PIK3CA, TP53, and ESR1 indicate that the diagnostic value of different genes is different, such as AUC for PIK3CA and TP53 were reported to be 0.96 (0.94–0.98) and 0.94 (0.91–0.95), respectively, and ESR1 had the lowest diagnostic value of 0.80 (0.76–0.83). Owing to the low sensitivity and AUC in the cases of CNV, there is no value for cfDNA-based detection of CNV based on insufficient amount of CNV data. This meta-analysis suggests that the detection of gene mutations in cfDNA have adequate diagnostic accuracy and can be used as an alternative to the tumor tissue for detection of SNV but not for CNV in BC yet.

/pdf/accuracy-of-analysis-of-cfdna-for-detection-of-single-3ie14j70w1.pdf

Accuracy of analysis of cfDNA for detection of single nucleotide variants and copy number variants in breast cancer.

Breast cancer is the most prevalent life-threatening cancer in women and the second leading cause of cancer associated deaths. Consequently, optimizing breast cancer therapy to increase cure rates in early stage disease and improve life expectancy and palliation for patients with metastasis is a critical need and major area of research in medical oncology. This article focuses on the development of personalized therapy in breast cancer though the use of targeted therapies and their associated biomarkers. Topics reviewed include the historic advances in targeting the HER2 receptor and the current avenues being studied to circumvent resistance; new developments in the management of triple negative and metastatic breast cancer; and the challenges and pitfalls associated with targeting angiogenesis. Using these as examples, many of the innovations and challenges in the treatment of women with breast cancer are explored.

The role of targeted therapy and biomarkers in breast cancer treatment

10512 Background: Mutations in PIK3CA, the gene encoding the p110α subunit of phosphoinositide-3-kinase (PI3K), are found in approx. 25% of breast cancers. Mutations are most commonly located on one of 3 hotspot locations on exons 9 and 20 of the gene. Inhibitors of PI3K are in clinical trials and expected to be of most therapeutic benefit among tumors that possess a somatic PIK3CA mutation. Traditional screening for such mutations relies on sequencing of formalin fixed paraffin-embedded (FFPE) tumor tissue. This prospective study was performed to evaluate the concordance of ‘BEAMing’ (named after the components of the method, namely beads, emulsification, amplification and magnetics) for somatic PIK3CA mutations using circulating tumor DNA (ctDNA) extracted from peripheral blood, compared to detection of mutations via sequencing of FFPE tissue. Methods: CtDNA was extracted from the peripheral blood of 60 women with MBC and screened for the presence of a PIK3CA mutation using the BEAMing method. Tumor DNA...

Improving detection methods for PIK3CA mutations in breast cancer using peripheral blood from patients with metastastic breast cancer (MBC).

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

E. Barnathan

Author Tools

Chat about Author

Papers

Improving detection methods for PIK3CA mutations in breast cancer using peripheral blood from patients with metastastic breast cancer (MBC).