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The prognostic value of PI3K mutational status in breast cancer: A meta-analysis.

ABSTRACT: Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular- functions and processes. The gene encoding for PI3K catalytic subunit p110? is mutated in 20-40% of BC. We performed a meta-analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor, and predictor of response to anti-cancer treatments. Overall 1929 cases were included. The pooled analysis confirmed that the presence of a PIK3CA mutation represents an independent negative prognostic factor (HR?=?1.67, 95%CI: 1.15-2.43; P?=?0.007) in BC, as previously reported. As PI3K signaling is also a result of other pathways' hyperactivation, further investigation of potential biomarkers able to predict likelihood of response to anti-PI3K/mTOR, anti-HER2, and other TKRs is warranted in future randomized clinical trials.

SUBMITTER: Sobhani N

PROVIDER: S-EPMC5995110 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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The prognostic value of PI3K mutational status in breast cancer: A meta-analysis.

Sobhani Navid N Roviello Giandomenico G Corona Silvia P SP Scaltriti Maurizio M Ianza Anna A Bortul Marina M Zanconati Fabrizio F Generali Daniele D

Journal of cellular biochemistry 20180301 6

Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular- functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20-40% of BC. We ...[more]

PMID: 29345357

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Project description:BackgroundHuman epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if HER2-low status has an independent impact on prognosis.Materials and methodsA systematic literature research was carried out to identify studies comparing survival outcomes of patients affected by HER2-low versus HER2-zero breast cancer. Using random-effects models, pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for progression-free survival (PFS) and overall survival (OS) in the metastatic setting as well as disease-free survival (DFS), OS and pathological complete response (pCR) in the early setting. Subgroup analyses by hormone receptor (HoR) status were carried out. The study protocol is registered on PROSPERO (n.CRD42023390777).ResultsAmong 1916 identified records, 42 studies including 1 797 175 patients were eligible. In the early setting, HER2-low status was associated with significant improved DFS (HR 0.86, 95% CI 0.79-0.92, P < 0.001) and OS (HR 0.90, 95% CI 0.85-0.95, P < 0.001) when compared to HER2-zero status. Improved OS was observed for both HoR-positive and HoR-negative HER2-low populations, while DFS improvement was observed only in the HoR-positive subgroup. HER2-low status was significantly associated with a lower rate of pCR as compared to HER2-zero status both in the overall population (OR 0.74, 95% CI 0.62-0.88, P = 0.001) and in the HoR-positive subgroup (OR 0.77, 95% CI 0.65-0.90, P = 0.001). In the metastatic setting, patients with HER2-low breast cancers showed better OS when compared with those with HER2-zero tumours in the overall population (HR 0.94, 95% CI 0.89-0.98, P = 0.008), regardless of HoR status. No significant PFS differences were found.ConclusionsCompared with HER2-zero status, HER2-low status appears to be associated with a slightly increased OS both in the advanced and early settings, regardless of HoR expression. In the early setting, HER2-low tumours seem to be associated to lower pCR rates, especially if HoR-positive.

Project description:Background: The correlation between programmed cell death-ligand 1 (PD-L1) which may affect T cell to form the immune tolerance and breast cancer (BC) still maintains to be uncovered. This meta-analysis was about to explore PD-L1 expression as well as its prognostic role in BC.Methods: First of all, we performed 3 databases: PubMed, Embase, and Web of Science to explore publications between January of 2015 and January of 2020. Strict inclusion and exclusion criteria were conducted: immunohistochemistry shall be used to detect target molecule expression and at least 1 survival indicator and related data we need should be included. The hazard ratio and 95% confidence interval were pooled related with survival as well as clinicopathological parameters. The effects of PD-L1 in differed aspects like sample size and age of each cohort were demonstrated by subgroup analyses as well as sensitivity analyses which may complain the potential source of heterogeneity. P?<?.05 indicates factors were charge of the heterogeneity of prognosis. Begg and Egger tests were used to identify publication bias.Results: We identified 12 studies containing a blanket of 4336 patients with BC for whom PD-L1 positive tumor cells were related with higher tumor stage, lymph node metastasis, estrogen receptor negativity, human epidermal growth factor receptor 2 positivity, luminal B and triple negative BC molecular subtype and high nuclear-associated antigen Ki- 67 expression. Meanwhile, compared to patients with PD-L1 negative expression, PD-L1 positivity associated with worse overall survival (Hazard ratio [HR]:1.43; 95% CI:0.98-2.10; P?<?.001) and might have no obvious tight connection with disease free survival (HR:1.40; 95% CI:1.11-1.78; P = .101) and recurrence free survival (HR:2.36; 95% CI:1.04-5.34; P?=?.145). The outcome of the meta-analysis was confirmed to be credible by sensitivity analysis. Publication bias was not existed indicated (P?=?.640).Conclusion: Positive PD-L1 expression has a worse clinical outcome in patients with BC demonstrated by our meta-analysis. Being urgent to catch attention to the role of PD-L1 in BC, it may be considered as prognostic marker of immune microenvironment for improving therapy efficacy.

Dataset Information

The prognostic value of PI3K mutational status in breast cancer: A meta-analysis.

Publications

The prognostic value of PI3K mutational status in breast cancer: A meta-analysis.

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