Independent Factor For Worse Survival Research Articles

RESTING ENERGY EXPENDITURE IMPACTS ON SHORT- AND LONG-TERM MORTALITY IN CRITICALLY ILL PATIENTS AFTER CARDIAC SURGERY- A RETROSPECTIVE ANALYSIS

<h3>Background</h3> It is well known that underfeeding and overfeeding of critically ill patients is harmful.¹ Even though it has been shown that administering nutrients at 70% of measured resting energy expenditure (REE) has a survival benefit, it was never assessed whether REE itself may be decreased in patients with adverse outcome. We therefore investigated whether REE measured via pulmonary artery catheter (PAC) impacts short- and long-term outcome after cardiac surgery comprising 30-day, 1-year and 1-6-year all-cause mortality. <h3>Methods</h3> We enrolled 596 consecutive patients who received a PAC prior to cardiac surgery for haemodynamic monitoring. Oxygen consumption (VO2) was determined from data obtained by the PAC during their ICU stay. REE was then calculated via the Fick equation and averaged over the first 7 days. Patients were divided into 2 groups depending on their REE being either above or below the median REE. Survival analysis was performed using the Kaplan Meier and multivariate Cox regression analysis for all-cause mortality. <h3>Results</h3> Patients with reduced REE, i.e., REE below the median of 1640 kcal/day, showed a significantly worse survival at 30-day and 1-year, but not for the period 1-6-years after cardiac surgery (Figure). In the multivariate cox regression, REE<=1640 remained an independent factor for worse survival after 1-year, even after adjusting for gender, age (4 groups <=55, 56-65, 66-75, >75), BMI (3 groups <=25, 26-30, >30) and length of surgery (2 groups <=6h, >6h) [REE<=1640: HR 2.2 (1.39; 3.51); (p<0.001)]. <h3>Conclusion</h3> Our findings indicate that reduced REE is associated with adverse outcome in patients after cardiac surgery emphasizing the importance of monitoring REE in critically ill patients either via indirect calorimetry or via PAC. Supplying nutrients based on calculated nutritional targets may cause overfeeding in vulnerable patients with reduced REE. <h3>References</h3> <ul><li>1. Zusman O, Theilla M, Cohen J, Kagan I, Bendavid I, Singer P. Resting energy expenditure, calorie and protein consumption in critically ill patients: a retrospective cohort study. Crit Care. 2016;20:367.</li></ul>

The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries

SummaryBackgroundRetinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival.MethodsWe did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models.FindingsThe cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope).InterpretationThis study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.FundingQueen Elizabeth Diamond Jubilee Trust.

Is adjuvant chemotherapy necessary for early gastric cancer?

Objective:To quantify the potential benefit of adjuvant chemotherapy (ACT) with respect to survival, and to identify factors for predicting prognoses in early gastric cancer patients.Methods:Patients with pT1 gastric cancer (GC) who underwent radical resection with D2 lymphadenectomy were retrospectively analyzed. Based on lymph node metastasis (LNM) status and treatment regimens, patients were classified into groups, and clinicopathological variables, overall survival (OS), and disease-specific survival (DSS) were compared.Results:Of 1,050 enrolled patients, 151 patients (14.4%) had a positive LNM status. Submucosal invasion, undifferentiated state, tumor size > 2 cm, ulceration, and lymphovascular invasion were independent risk factors for LNM using multivariate analyses. The 5-year OS of all patients was 96.4%. HER2 positive, perineural invasion, and LNM were independent factors for worse survival. Patients with pT1N3 GC had a worse 5-year OS and DSS than pT1N0, pT1N1, and pT1N2 patients (P < 0.001). The 5-year OS and DSS for pT1N1 patients showed no significant difference between ACT and surgery only patients. For pT1N2 patients, the 5-year OS and DSS showed no significant difference between S-1 and Xelox treatments. For pT1N3 patients, 7 (36.8%) received S-1, while 12 (63.2%) received Xelox treatment. Patients receiving Xelox treatment showed a better 5-year OS (75.0% vs. 14.3%) and DSS (81.8% vs. 20.0%) than patients receiving S-1 (P < 0.05).Conclusions:Curative surgery only was adequate for patients with pT1N0 and pT1N1. Xelox showed no survival benefits for pT1N2 patients. Therefore, S-1 is the optimal choice for pT1N2 patients, when considering adverse effects. Xelox is recommended for pT1N3 patients.

Scoring systems for PD-L1 expression and their prognostic impact in patients with resectable gastric cancer.

The combined positive score (CPS) and tumor proportion score (TPS) have been developed to evaluate programmed death ligand-1 (PD-L1) expression, especially due to the potential benefit of the targeted therapy. However, the prognostic value of PD-L1 scoring systems in gastric cancer (GC) remains unclear. This study aimed to evaluate PD-L1 expression according to CPS and TPS in curative resected GC patients and its correlation with prognosis. We retrospectively evaluated 284 GC patients who underwent D2-gastrectomy by tissue microarray. PD-L1 expression was analyzed by immunohistochemistry. PD-L1 positivity by CPS and TPS was observed in 45 (15.8%) and 34 (12%) patients, respectively. Larger tumor size (p = 0.028), undetermined Lauren type (p < 0.001), and heavy inflammatory infiltrate (p = 0.009) were associated with CPS-positive GC. TPS-positive were more frequent in patients with larger tumor size (p = 0.004), undetermined type (p < 0.001), moderate/severe inflammatory infiltrate (p = 0.001), total gastrectomy (p = 0.036), and poorly differentiated histology (p = 0.025). No differences were observed in the pT, pN, and pTNM status according to the PD-L1 scores. Both scores were associated with Epstein-Barr virus positivity, microsatellite instability and p53-normal expression. The disease-free survival (DFS) was worse for CPS-negative compared to CPS-positive group (p = 0.052). No difference was observed between TPS-positive and negative groups (p = 0.436). Total gastrectomy, advanced pT status, and CPS-negative were independent factor for worse survival in GC. CPS was an independent prognostic factor for survival and could be used as a prognostic biomarker in patients with resectable GC.

LncRNA TCL6 correlates with immune cell infiltration and indicates worse survival in breast cancer.

Long non-coding RNA (lncRNA) T-cell leukemia/lymphoma 6 (TCL6) has been reported as a potential tumor suppressor. However, its expression and function in breast cancer remain unknown. This study was performed to investigate the expression of lncRNA TCL6 in breast cancer and its clinical significance. The survival and clinical molecular roles of TCL6 in breast cancer were analyzed. The underlying mechanism modulated by TCL6 and its correlation with immune-infiltrating cells were investigated. Gene Expression Omnibus (GEO) datasets were further used to confirm the prognostic role of TCL6. TCL6 low expression was not correlated with age, clinical stage, T stage, lymph node metastasis, distant metastasis, human epidermal growth factor 2 status, but was associated with estrogen receptor and progesterone receptor (PR) status and was an independent factor for worse survival (HR 1.876, P = 0.016). Specifically, low TCL6 expression correlated with worse prognosis in PR-negative patients. TCL6 could predict worse survival in luminal B breast cancer based on intrinsic subtypes. Immune-related pathways such as Janus kinase-signal transducer of activators of transcription were regulated by TCL6. Further finding revealed that TCL6 correlated with immune infiltrating cells such as B cells (r = 0.25, P < 0.001), CD8+ T cells (r = 0.23, P < 0.001), CD4+ T cells (r = 0.25, P < 0.001), neutrophils (r = 0.21, P < 0.001), and dendritic cells (r = 0.27, P < 0.001). TCL6 was also positively correlated with tumor-infiltrating lymphocytes infiltration and PD-1, PD-L1, PD-L2, and CTLA-4 immune checkpoint molecules (P < 0.001). Our findings suggest that lncRNA TCL6 correlates with immune infiltration and may act as a useful prognostic molecular marker in breast cancer.

Malignant Pleural Effusion at Presentation in Patients with Small-Cell Lung Cancer

Background: Malignant pleural effusion (MPE) is commonly seen in patients with non-small cell lung cancer. However, the prevalence of MPE at presentation in small-cell lung cancer (SCLC) is not reported and the clinical impact of MPE at presentation on patients with SCLC remains largely unknown. Objective: The objective of this study is to assess the occurrence rate of MPE and its prognostic implications at presentation in patients with SCLC. Method: We used the Surveillance Epidemiology and End Results (SEER) registry to extract data from patients with SCLC diagnosed between 2004 and 2014. The Kaplan–Meier method was used to estimate the overall survival and the Cox proportional hazard model was used to evaluate whether MPE was an independent risk for outcome. Results: Among the 68,443 patients with SCLC, MPE was present in 7,639 (11.16%). The probability of MPE was higher in older patients with larger tumors and mediastinal lymph node involvement at presentation. Median overall survival (3 vs. 7 months), estimated 1-year survival (17 vs. 30%), and 2-year survival (6 vs. 14%) were significantly lower in patients with MPE than without MPE, respectively (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.41–1.50, p< 0.001). MPE was also an independent factor for worse survival in multivariate analysis (HR 1.36, 95% CI 1.32–1.41, p < 0.001). Conclusions: MPE is common at presentation (11%) in patients with SCLC and may be associated with decreased survival. Additional studies are required to assess the treatment-adjusted survival rate in the setting of MPE.

Prognostic value of Ki67 and p63 expressions in bladder cancer patients who underwent radical cystectomy.

Radical cystectomy (RC) is the gold standard treatment for patients with high-risk non-muscle-invasive bladder cancer and muscle-invasive bladder cancer (MIBC) . However, despite aggressive treatment, mortality rates of patients are still high. Therefore, it is crucial to indentify some practical prognostic factors for cancer-specific survival in those patients to guide our therapeutic strategies. We included 103 patients treated with RC for urothelial bladder cancer (UBC) between July 2007 and June 2014 in our institution and analyzed their clinicopathological parameters. The mean follow-up was 22 months (range 2-89 months). Advanced tumor T stage, N stage, ABO blood type, a history of DM and positive p63 expression were independent factors for worse survival in all patients who underwent RC. Moreover, in female gender, high Ki67 expression was significant risk factor for cancer-specific survival (CSS) in MIBC patients. Our study demonstrated that immunohistochemical expressions of Ki67 and p63 are potential prognostic factors for UBC patients who underwent RC.

Predictive Value of Clinicopathological Markers for the Metachronous Bladder Cancer and Prognosis of Upper Tract Urothelial Carcinoma

Upper tract urothelial carcinoma (UTUC) is rare but aggressive with poor prognosis. We aimed to find effective predictive markers for recurrence and prognosis in UTUC patients. In this retrospective study, we included 88 UTUC patients treated with radical neprhoureterectomy (RNU) and analyzed their clinicopathological parameters. For study of incidence of metachronous bladder tumor, models were adjusted with inclusion of prophylactic intravesical instillation chemotherapy. The mean follow-up was 28.59 months (2 to 82 mo). Lack of gross hematuria (RR 0.060, 95%CI 0.008–0.468), tumor located at ureter (RR 0.037, 95%CI 0.004–0.378), advanced stage and higher p53 expression were independent factors for worse survival. Recurrence of bladder cancer occurred 20% of patients at median follow-up of 37.65 months (5 to 82 mo). Higher tumor grade (RR 5.998, 95%CI 1.359–26.479) and presence of ipsilateral non-functioning kidney at diagnosis (RR 5.982, 95%CI 1.338–26.750) were predictors for recurrence. The present study identified several parameters with predictive value in the prognosis and intravesicle recurrence in UTUCand shed light on the better monitoring and management of the disease.

The impact of intracytoplasmic mucin in lung adenocarcinoma with pneumonic radiological presentation

ObjectivesThis study investigated the clinical and prognostic impact of intracytoplasmic mucin in lung adenocarcinoma with “pneumonic” radiological presentation, formerly known as bronchioloalveolar carcinoma (BAC). Patients and methodsBetween 1986 and 2011, clinical and pathological data from 120 consecutive patients with lung adenocarcinoma with “pneumonic” radiological presentation were reviewed. Intracytoplasmic mucin was assessed using a diastase-resistant periodic acid-Schiff staining. The presence of EGFR or K-Ras mutations and ALK rearrangement were determined in surgical samples. ResultsThe two predominant histological patterns were invasive mucinous adenocarcinoma (40%) and lepidic predominant adenocarcinoma (32%). Intracytoplasmic mucin was detected in 71 patients (59.2%) who were more likely to be non-smokers (p=0.04) and have bronchorrhea (p=0.006), crepitant rales (p=0.02), or neutrophil alveolitis (p=0.0004). In mucin-producing tumors, EGFR mutation was not detected, K-Ras mutations and ALK rearrangement were present in 32% and 3% of cases, respectively. In non-mucin-producing tumors, EGFR and K-Ras mutations were detected in 17% and 10% of cases, respectively, no ALK rearrangement was detected. In univariate analysis, performance status>0, crepitant rales, bronchorrhea, neutrophil alveolitis, bilateral extension, intracytoplasmic mucin and no surgery were associated with worse survival. In multivariate analyses, intracytoplasmic mucin, neutrophil alveolitis, and no surgery were independent factors for worse survival. ConclusionIntracytoplasmic mucin is associated with specific clinical characteristics and is an independent factor for worse survival in lung adenocarcinoma formerly known as BAC.

Abstract P6-06-12: Prognostic significance of pretreatment neutrophil/-lymphocyte ratio in breast cancer: A meta-analysis

Abstract Background: There is an increasing body of evidence that the host inflammatory response plays an important prognostic role in cancer. High level of the neutrophil/lymphocyte ratio (NLR) has been associated with poor prognosis in many cancers. The association of NLR with survival in breast cancer and its different subtypes remains unclear. Methods: A literature review of electronic databases was conducted to identify studies exploring the prognostic role of NLR in breast cancer. Data were extracted from individual publications or estimated from associated figures. Where possible, data were included in a meta-analysis. The association of high NLR with other classical prognostic factors (e.g. tumor size, histological grade, nodal metastasis, and estrogen receptor or HER2/neu expression) was evaluated using the Mantel-Haenszel odds ratio (OR). Both univariable and multivariable analyses of NLR with overall survival (OS) were assessed using generic inverse variance. Subgroup analysis was conducted to assess the effect of different cut-offs to define high versus low NLR. Breast cancer-specific survival was assumed to be equivalent to OS if non-breast cancer deaths contributed to &amp;lt;5% of evaluable patients. Results: The analysis included a total of 5 retrospective studies comprising of 3,449, predominantly early-stage, breast cancer patients. Three studies defined high NLR based on the most discriminating cut-off evaluated by receiver operator characteristic (ROC) analysis, while two studies compared upper to lower quartiles for NLR. The mean age was 56.9 and there were no differences in age between those with high and low NLR (mean difference +1.54 years, 95% confidence intervals [CI] -0.17-3.24, P = 0.08). Compared with low NLR, patients with high NLR were more likely to have tumors larger than 2cm (OR 1.69, 95% CI 1.23-2.32, P = 0.001), nodal metastases (OR 1.65, 95% CI 1.21-2.23, P = 0.001) and HER2/neu overexpression or amplification (OR 1.77, 95% CI 1.20-2.62, P = 0.004). There were no differences in the proportion of tumors that were high grade (OR 1.27, 95% CI 0.90-1.79, P = 0.18) or estrogen receptor positive (OR 0.76, 95% CI 0.54-1.09, P = 0.13) between those with high and low NLR. High NLR showed an association with worse OS (univariable hazard ratio [HR] 3.42, 95% CI 2.75-4.24, P&amp;lt;0.001). This association was retained in multivariable analyses (HR 3.16, 95% CI 2.13-4.68, P&amp;lt;0.001). There was no difference in this association with worse survival when NLR was assessed based on a single cut-off or when compared between upper and lower quartiles (subgroup difference P = 0.68, table). Conclusion: High NLR is associated with various poor prognostic factors, but despite this appears to be an independent factor for worse survival from breast cancer. These findings may be explained by an adverse host response to cancer. SubgroupNumber of studiesHR for OS95% CIPCut-off determined by ROC analysis33.362.64-4.29&amp;lt;0.001Upper versus lower quartile23.872.08-7.23&amp;lt;0.001 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-12.

Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma

BackgroundAccumulating evidence indicates that components of the systemic inflammatory response, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis of various cancers. We aimed to elucidate whether CRP and NLR could serve as potential surrogate markers for response and survival in patients with hepatocellular carcinoma (HCC).MethodsThe study population consisted of 318 consecutive patients with HCC. CRP and NLR were measured at baseline with follow-up measurements.ResultsWith the mean follow-up of 13.9 months, the median survival time was 13.8 months. Child-Pugh class, tumor size > 5 cm, tumor multiplicity, presence of portal vein thrombosis, α-fetoprotein > 200 ng/mL, CRP > 6.3 mg/L and NLR > 2.3 were identified as independent factors for worse survival of HCC (all p < 0.05). Patients with elevated CRP (> 6.3 mg/L) and elevated NLR (> 2.3) had a significantly shorter overall survival than those with low CRP and low NLR (all p < 0.001). The combined use of CRP and NLR provided incremental prognostic information. With significant inter-correlations, levels of CRP and NLR escalated with aggravating Child-Pugh class from A to C or progressing tumor stage from I to IV. CRP and NLR on baseline and serial measurements were well predictive of treatment response (p < 0.001).ConclusionsCRP and NLR are independent indicators for survival in HCC patients, reflecting tumor burden and hepatic reserve. Their role in predicting tumor response and survival is more enhanced when used in combination. This study suggests that CRP and NLR are important prognostic biomarkers for HCC.

Prognostic Impact of Malignant Pleural Effusion at Presentation in Patients with Metastatic Non–Small-Cell Lung Cancer

Despite its common occurrence, the influence of malignant pleural effusion (MPE) on the outcomes of patients with advanced non-small-cell lung cancer (NSCLC) with distant metastasis (M1b) is unknown. We evaluated the clinical characteristics associated with MPE at presentation and the prognostic impact of MPE at presentation in patients with stage M1b NSCLC. We extracted data from the Surveillance Epidemiology and End Results (SEER) registry from patients with NSCLC diagnosed between 2004 and 2005. Odds-ratio estimates were calculated using logistic regression, and the Kaplan-Meier method was used to estimate the overall survival. Cox proportional hazard model was used to evaluate whether MPE was an independent risk for outcome. Among the 57,685 patients, MPE was present in 9170 (15.9%), including 3944 out of 31,506 (12.5%) without distant metastases and 5226 (20.0%) out of 26,179 with M1b. The probability of MPE was higher in patients with larger tumors, mediastinal lymph node involvement, and adenocarcinoma, NSCLC not otherwise specified, or large-cell histology. In patients with stage M1b, median overall survival (3 months versus 5 months), estimated 1-year survival (12.6% versus 24.8%), and 2-year survival (5.4% versus 11.3%) were significantly lower in patients with MPE compared with those without MPE (hazards ratio 1.49, 95% confidence interval 1.44-1.54, p < 0.0001). MPE was also an independent factor for worse survival in multivariate analysis (hazards ratio 1.36, 95% confidence interval1.30-1.43, p < 0.001). MPE is a common complication in patients with NSCLC and is associated with decreased survival in patients with distant metastases. If these data are validated, subsequent studies in patients with advanced NSCLC may consider stratification according to the MPE status.

FOXP3+ cell density in lymphoid follicles from histologically normal mucosa is a strong prognostic factor in early stage colon cancer.

There are few clearly established prognostic factors available to guide the use of adjuvant chemotherapy in early stage colon cancer patients. Some of the most promising candidates include the invasion of extramural blood vessels by tumour cells and the densities of FOXP3+ T regulatory cells (Tregs) in tumour and adjacent normal colonic mucosal tissue. The aim of our study was to evaluate the prognostic significance of these markers in AJCC stage II colon cancer, with particular reference to lymphoid follicles in the mucosa. Histopathological review for the presence of vascular and serosal invasion was conducted on a series of 165 stage II colon cancers treated by surgery alone. Immunohistochemical staining for FOXP3 was performed on tumour tissue and histologically normal colonic mucosa from the surgical margin. Image analysis software was used to evaluate the density of FOXP3+ cells in the tumour core, invading margin and lymphoid follicles from the colonic mucosa. For survival analysis, cases were classified into high- or low-density of FOXP3+ cells according to the median value. The mean density of FOXP3+ Tregs in lymphoid follicles was twofold and fivefold higher than in the invading margin and tumour core, respectively. Multivariate analysis identified extramural vascular invasion (HR, 2.47; 95% CI: 1.00-6.07; P=0.05) and high FOXP3+ cell density in lymphoid follicles (HR, 4.22; 95% CI: 1.49-11.91; P=0.007) as independent factors for worse survival, whereas a high frequency of lymphoid follicles in histologically normal colonic mucosa was associated with better survival (HR, 0.31; 95% CI: 0.12-0.79; P=0.014). Our data suggest that host factors related to the immune system have major prognostic significance in early stage colon cancer. The density of FOXP3+ cells within lymphoid follicles and the frequency of these structures in normal colonic mucosa represent novel and independent prognostic factors.

Different prognostic factors for survival in acute and lymphomatous adult T-cell leukemia/lymphoma

Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a clinically aggressive and heterogeneous entity; hence it is likely that different variants of ATLL have different prognostic factors. Methods: 95 patients with ATLL seen at our institution between 1987 and 2008 were included. Clinical data were compared, according to ATLL variant, using the Mann–Whitney and the Chi-square tests for continuous and categorical variables, respectively. Kaplan–Meier estimates compared using the log-rank test and Cox proportional-hazard test were used for the univariate and multivariate analysis, respectively. Results: Median age was 61 years with male-to-female ratio of 1.07:1. Patients with acute ATLL were more likely to present with bone marrow, liver and spleen involvement, higher β2-microglobulin and lower albumin levels. Poor performance status, high IPI score, presence of B symptoms, high LDH and low albumin levels were associated with a worse survival in lymphomatous ATLL. High LDH, high β2-microglobulin and high PIT score were associated with worse survival in acute ATLL. In the multivariate analysis, low albumin level and presence of B symptoms were independent factors for worse survival in lymphomatous ATLL, and high β2-microglobulin level was independent factor for worse survival in acute ATLL. Conclusions: Aggressive ATLL variants have a distinct, almost mutually exclusive profile of prognostic factors.

Phosphatidylinositol 3-Kinase in Breast Cancer: Where from Here?

In recent years, the pivotal role that phosphatidylinositol 3-kinase (PI3K) alterations can have in cancer has largely expanded as a result of intensive studies on new functions and alterations in human cancer. We now know that PI3K-Akt pathway is relevant for several fundamental cellular functions

PIK3CA mutations in breast cancer are associated with poor outcome

The phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathway is considered to play an important role in tumorigenesis. Frequent somatic mutations in the PI3K subunit p110alpha (PIK3CA) occur in a variety of cancer types. We screened 250 primary human breast tumors for mutations in PIK3CA in order to determine associations with pathological features and with patient outcome. The frequency of PIK3CA mutations in the C2, helical and kinase domains was 35% (88/250). Mutations were associated with larger tumor size (p = 0.004) and positive estrogen receptor status (p = 0.008). Patients with PIK3CA mutations showed significantly worse survival (p = 0.004), particularly those with positive estrogen receptor expression or non-amplified erbB2 (both p = 0.002). PIK3CA mutation was an independent factor for worse survival in breast cancer patients with non-amplified erbB2 (RR = 2.6, 95%CI [1.2-5.5], p = 0.016).