PIK3CA mutations in breast cancer: reconciling findings from preclinical and clinical data

Zardavas, Dimitros; Phillips, Wayne A.; Loi, Sherene

doi:10.1186/bcr3605

Cited by 110 publications

(72 citation statements)

References 78 publications

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“…These results support recommendations of using these two makers, beside ER, PR and HER2 negativity, as additional surrogates in characterising breast cancers with basal phenotype [25]. Moreover, the roles played by PIK3CA in BC progression through its downstream effectors, especially through driving an epithelial-to-mesenchymal transition program (EMT) with up regulation of N-cadherin and P-cadherin has been reported in the same series [26,27], as well as in others [28].…”

Section: Discussionsupporting

confidence: 84%

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

Aleskandarany

Soria

Green

et al. 2015

Breast Cancer Res Treat

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Accurate distant metastasis (DM) prediction is critical for risk stratification and effective treatment decisions in breast cancer (BC). Many prognostic markers/models based on tissue marker studies are continually emerging using conventional statistical approaches analysing complex/dimensional data association with DM/poor prognosis. However, few of them have fulfilled satisfactory evidences for clinical application. This study aimed at building DM risk assessment algorithm for BC patients.A well-characterised series of early invasive primary operable BC (n=1902), with immunohistochemical (IHC) expression of a panel of biomarkers (n=31) formed the material of this study. Decision tree algorithm was computed using WEKA software, utilising quantitative biomarkers' expression and the absence/presence of distant metastases.Fifteen biomarkers were significantly associated with DM, with six temporal subgroups characterised based on time-to-development of DM ranging from < 1 year to > 15 years of follow-up. Of these 15 biomarkers, 10 had a significant expression pattern where Ki67LI, HER2, p53, N-cadherin, P-cadherin, PIK3CA and TOMM34 showed significantly higher expressions with earlier development of DM. In contrast, higher expressions of ER, PR, and BCL2, were associated with delayed occurrence of DM. DM prediction algorithm was built utilising cases informative for the 15 significant markers. Four risk groups of patients were characterised. Three markers; p53, HER2 and BCL2 predicted the probability of DM, based on software-generated cut-offs, with a precision rate of 81.1% for positive predictive value and 77.3%, for the negative predictive value.This algorithm reiterates the reported prognostic values of these three markers and underscores their central biologic role in BC progression. Further independent validation of this pruned panel of biomarkers is therefore warranted.3

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Section: Discussionsupporting

confidence: 84%

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

Aleskandarany

Soria

Green

et al. 2015

Breast Cancer Res Treat

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“…PIK3CA mutations represent one of the most common genetic aberrations in breast cancer [68]. In a study on 241 patients with breast cancer, PIK3CA mutations were found in 15.8% cases [69].…”

Section: Leptin Biology and Molecules Of Relevant Signal Transductmentioning

confidence: 99%

The potential role of leptin in tumor invasion and metastasis

Ray

Cleary

2017

Cytokine & Growth Factor Reviews

114

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The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin’s association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways. For example, leptin is associated with a number of biological components that could lead to tumor cell invasion and distant metastasis. This includes interactions with carcinoma-associated fibroblasts, tumor promoting effects of infiltrating macrophages, activation of matrix metalloproteinases, transforming growth factor-β signaling, etc. Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis. Furthermore, leptin’s potentiating effects on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis, leptin has been shown to influence both adenocarcinomas and squamous cell carcinomas. Features of poor prognosis such as tumor invasion, lymph node involvement and distant metastasis have been recorded in several cancer types with higher levels of leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general, obesity indicates poor prognosis in cancer patients.

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“…PI3K signaling is upregulated in an estimated 70% of breast cancers (Leroy et al 2016), whether as a consequence of increased IGF1R (or EGFR) pathway activation, or secondary to oncogenic mutations in PIK3CA, reported to occur in about 25% of all breast cancers (Zardavas et al 2014). IGF1R pathway activation is known to confer resistance to PI3K inhibition (Leroy et al 2016), suggesting the possible utility of combined IGF1R/PI3K inhibition.…”

Section: Pi3k Inhibitorsmentioning

confidence: 99%

Combination therapy approaches to target insulin-like growth factor receptor signaling in breast cancer

Ochnik

Baxter

2016

Endocrine-Related Cancer

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Insulin-like growth factor receptor (IGF1R) signaling as a therapeutic target has been widely studied and clinically tested. Despite the vast amount of literature supporting the biological role of IGF1R in breast cancer, effective clinical translation in targeting its activity as a cancer therapy has not been successful. The intrinsic complexity of cancer cell signaling mediated by many tyrosine kinase growth factor receptors that work together to modulate each other and intracellular downstream mediators in the cell highlights that studying IGF1R expression and activity as a prognostic factor and therapeutic target in isolation is certainly associated with problems. This review discusses the current literature and clinical trials associated with IGF-1 signaling and attempts to look at new ways of designing novel IGF1R-directed breast cancer therapy approaches to target its activity and/or intracellular downstream signaling pathways in IGF1R-expressing breast cancers. 23:11 Review A M Ochnik and R C BaxterDual IGF-directed breast cancer therapies

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PIK3CA mutations in breast cancer: reconciling findings from preclinical and clinical data

Cited by 110 publications

References 78 publications

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

The potential role of leptin in tumor invasion and metastasis

Combination therapy approaches to target insulin-like growth factor receptor signaling in breast cancer

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