Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis

Pang, Bo; Cheng, Shi; Sun, Shipeng; An, Cheng; Liu, Zhiyuan; Xue, Feng; Liu, Guijian

doi:10.1038/srep06255

Cited by 70 publications

(70 citation statements)

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“…A meta-analysis including 26 studies demonstrated a significant association between PIK3CA mutations and ER and progesterone receptor (PR) expression (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.65-2.23; OR 1.88, 95% CI 1.61-2.20, respectively) [17]. Although these mutations often occur in ER-positive breast carcinomas, their clinical relevance and their prognostic and predictive value are still matters of debate.…”

Section: Mutations In the Pi3k Signaling Pathway And Their Prognosticmentioning

confidence: 99%

“…A meta-analysis including 5 studies noted a significant correlation between PIK3CA mutations and a better recurrence-free survival (hazard ratio (HR) 0.76, 95% CI 0.59-0.98; P = 0.03) [17]. Another meta-analysis including 6 studies found a similar result in relation to disease-free survival (HR 0.72, 95% CI 0.57-0.91; P = 0.006) [21].…”

Section: Mutations In the Pi3k Signaling Pathway And Their Prognosticmentioning

confidence: 99%

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The PI3K Pathway: Background and Treatment Approaches

Lux¹,

Fasching²,

Schrauder³

et al. 2016

Breast Care

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Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance. Understanding the way in which resistance develops is therefore essential for developing treatment approaches that can prevent or reverse endocrine resistance. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role here. As a result of the numerous interactions involved, complex issues arise that need to be taken into account in the development and use of therapeutic agents. In addition, this signaling pathway is the one that most frequently undergoes mutations in breast cancer. The prognostic and predictive significance of individual mutations has not yet been fully explained, but it might provide a basis for patient selection in clinical studies. Initial research results on the use of PI3K inhibitors suggest that this may be a highly promising therapeutic approach, with an acceptable side effect profile.

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Section: Mutations In the Pi3k Signaling Pathway And Their Prognosticmentioning

confidence: 99%

Section: Mutations In the Pi3k Signaling Pathway And Their Prognosticmentioning

confidence: 99%

The PI3K Pathway: Background and Treatment Approaches

Lux¹,

Fasching²,

Schrauder³

et al. 2016

Breast Care

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“…breast invasive carcinoma (BRCA), Fig. 3; the genes selected as the baseline (PIK3CA, KRAS, SF3B1, RET, ERBB2, TP53, MAP3K1, GATA3, CDH1, RUNX1, RB1, ARID1A) have been previously found as mutated in breast cancer 15,[26][27][28] ;…”

Section: Results Of the Optimized 20/20 Rule In Each Data Setmentioning

confidence: 99%

Identifying cancer type specific oncogenes and tumor suppressors using limited size data

Pavel

Vasile

2016

J. Bioinform. Comput. Biol.

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Cancer is a complex and heterogeneous genetic disease. Di®erent mutations and dysregulated molecular mechanisms alter the pathways that lead to cell proliferation. In this paper, we explore a method which classi¯es genes into oncogenes (ONGs) and tumor suppressors. We optimize this method to identify speci¯c (ONGs) and tumor suppressors for breast cancer, lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and colon adenocarcinoma (COAD), using data from the cancer genome atlas (TCGA). A set of genes were previously classi¯ed as ONGs and tumor suppressors across multiple cancer types (Science 2013). Each gene was assigned an ONG score and a tumor suppressor score based on the frequency of its driver mutations across all variants from the catalogue of somatic mutations in cancer (COSMIC). We evaluate and optimize this approach within di®erent cancer types from TCGA. We are able to determine known driver genes for each of the four cancer types. After establishing the baseline parameters for each cancer type, we identify new driver genes for each cancer type, and the molecular pathways that are highly a®ected by them. Our methodology is general and can be applied to di®erent cancer subtypes to identify speci¯c driver genes and improve personalized therapy.

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“…One important question is the possible effect of PIK3CA status on cancer outcome and treatment efficacy. Notably, many studies examining the prognostic significance of PIK3CA mutations in breast cancer [35] have been published, however very few included a large enough number of patients [3,14,19,[22][23][24][25][26][27][28][29][30][31][32][33][34]. Also, less than half of them [22,24,26,28,30,31,33] used data from clinical trials, thus excluding the effect of treatment heterogeneity when evaluating prognostic factors.…”

Section: Discussionmentioning

confidence: 99%