Prognostic Significance of High VEGF-C Expression for Patients with Breast Cancer: An Update Meta Analysis

BackgroundThe prognostic significance of vascular endothelial growth factor C (VEGF-C) expression in breast cancer (BC) patients remains controversial. Therefore, this meta-analysis was performed to determine the prognostic significance of VEGF-C expression in BC patients.ResultsThe present meta analysis totally included 21 eligible studies and 2828 patients with BC. The combined HRs were 1.87(95% CI 1.25–2.79, P = 0.001) for DFS and 1.96(95% CI 1.15–3.31, P = 0.001) for OS. The pooled HRs of non-Asian subgroup were 2.04(95%CI 1.36–3.05, P = 0.001) for DFS and 2.61(95%CI 1.51–4.52, P = 0.001) for OS, which were significantly higher than that of Asian subgroup. The funnel plot for publication bias was symmetrical. The further Egger''s test and Begg''s test did not detect significant publication bias (all P>0.05).ConclusionsThe present meta analysis strongly supported the prognostic role of VEGF-C expression for DFS and OS in BC patients, especially for patients in non-Asian countries. Furthermore, stratification by VEGF-C expression may help to optimize the treatments and the integrated managements for BC patients.     

Prediction of Poor Prognosis in Breast Cancer Patients Based on MicroRNA-21 Expression: A Meta-Analysis

BackgroundMicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer.MethodsThe meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigated the association between miR-21 expression and survival outcomes in breast cancer patients. With respect to survival outcomes, the pooled hazard ratios (HRs) of miR-21 were calculated given a 95% confidence interval (CI).ResultsOur meta-analysis identified a total of 10 studies involving 1,439 cases. Further investigation demonstrated that a high miR-21 expression can predict poor overall survival (OS) (HR = 2.57, 95% CI: 1.37—4.81, P = 0.003) and shortened disease-free/recurrence-free survival (DFS/RFS) (HR = 1.45, 95% CI: 1.16—1.82, P = 0.001) in breast cancer patients. Moreover, high miR-21 expression was significantly correlated with lowered OS in the Asian group (HR = 5.07, 95% CI: 2.89—8.92, P < 0.001), but not in the Caucasian cohort (HR = 1.44, 95% CI: 0.99—2.10, P = 0.058). Furthermore, odds ratios (ORs) showed that up-regulated miR-21 levels were associated with multiple clinical characteristics.ConclusionOur results indicated that miR-21 can predict unfavorable prognoses in breast cancer patients, especially in Asians.     

Harmonic Scalpel versus Electrocautery Dissection in Modified Radical Mastectomy for Breast Cancer: A Meta-Analysis

Background

Despite the common use of conventional electrocautery in modified radical mastectomy for breast cancer, the harmonic scalpel is recently emerging as a dominant surgical instrument for dissection and haemostasis, which is thought to reduce the morbidity, such as seroma and blood loss. But the results of published trials are inconsistent. So we made the meta-analysis to assess the intraoperative and postoperative endpoints among women undergoing modified radical mastectomy with harmonic scalpel or electrocautery.

Methods

A comprehensive literature search of case-control studies from PubMed, MEDLINE, EMBASE and Cochrane Library databases involving modified radical mastectomy with harmonic scalpel or electrocautery was performed. We carried out a meta-analysis of primary endpoints including postoperative drainage, seroma development, intraoperative blood loss and secondly endpoints including operative time and wound complications. We used odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the effect size for categorical outcomes and standardised mean differences (SMDs) for continuous outcomes.

Results

A total of 11 studies with 702 patients were included for this meta-analysis. There was significant difference in total postoperative drainage (SMD: -0.74 [95%CI: -1.31, -0.16]; P< 0.01), seroma development[OR: 0.49 (0.34, 0.70); P < 0.01], intraoperative blood loss(SMD: -1.14 [95%CI: -1.81,-0.47]; P < 0.01) and wound complications [OR: 0.38 (0.24, 0.59); P < 0.01] between harmonic scalpel dissection and standard electrocautery in modified radical mastectomy for breast cancer. No difference was found as for operative time between harmonic scalpel dissection and standard electrocautery (SMD: 0.04 [95%CI: -0.41, 0.50]; P = 0.85).

Conclusion

Compared to standard electrocautery, harmonic scalpel dissection presents significant advantages in decreasing postoperative drainage, seroma development, intraoperative blood loss and wound complications in modified radical mastectomy for breast cancer, without increasing operative time. Harmonic scalpel can be recommended as a preferential surgical instrument in modified radical mastectomy.     

The impact of chemokine receptor CXCR4 on breast cancer prognosis: A meta-analysis

Background: C-X-C chemokine receptor type 4 (CXCR4) has been implicated in the invasiveness and metastasis of diverse cancers. However, the published data remain controversial on the correlation between CXCR4 expression level, as well as its subcellular distribution in tumor cells, and the clinical outcome of patients with breast cancer. Methods: To identify the precise role of CXCR4 in the clinical outcome of breast cancer, we performed a meta-analysis including 15 published studies. Original data included the hazard ratios (HRs) of overall survival (OS) and disease-free survival (DFS) in breast cancer with high CXCR4 expression versus low expression. We pooled hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the hazard. Results: A total of 15 published studies (including 3104 patients) were eligible. Overall survival (OS) and disease-free survival (DFS) of breast cancer were found to be significantly related to CXCR4 expression level, with the HR being 1.65 (95%CI: 1.34–2.03; P < 0.00001) and 1.94 (95%CI: 1.42–2.65; P < 0.00001) respectively. Stratified analysis according to subcellular distribution of CXCR4 showed that high expression in whole cells, cytoplasm and nucleus could predict unfavorable OS, with the HR of 2.02 (95%CI: 1.43–2.85; P < 0.0001), 1.57 (95%CI: 1.13–2.18; P = 0.007), and 1.47 (95%CI: 1.19–1.81; P = 0.0004) respectively. As for DFS, elevated expression level of CXCR4 both in whole cells and cytoplasm predicted a poor outcome, with the HR being 2.23 (95%CI: 1.48–3.37; P = 0.0001) and 1.76 (95%CI: 1.11–2.80; P = 0.02), while high expression in the nucleus had no statistical significance, with HR 1.15 (95%CI: 0.52–2.55; P = 0.73). Conclusions: Increased CXCR4 expression, especially in whole cells and cytoplasm, may serve as a poor prognostic indicator in patients with breast cancer. Future studies are warranted to investigate the relationship between CXCR4 expression and survival of patients with breast carcinoma, which could help predict the clinical outcome and guide clinical decision-making for therapy.     

Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review

BackgroundBreast cancer (BC) is the most common cancer for women all over the world. Great interests have been paid to discover accurate and noninvasive methods for breast cancer diagnosis and prognosis. Although the diagnostic and prognostic value of microRNA-200 (miRNA- 200, miR-200) family has been revealed in many studies, the results were inconsistent. Thus, this meta-analysis aims to assess the overall value of miRNA-200 family in breast cancer diagnosis and prognosis.MethodRelevant studies were searched from the following databases: PubMed, PMC, EMBASE, and ScienceDirect using key words: ("miRNA-200 family" or "miR-141" or "miR-200a" or "miR-200b" or "miR-200c" or "miR-429") and (“HER2” or “Luminal A” or “Luminal B” or “TNBC”) and ("breast cancers" or "breast carcinoma" or "breast malignancy" or "breast tumor"). The sensitivity, specificity, AUC were then calculated to estimate the diagnostic accuracy of the miR-200 family. As for the prognostic value of the miR-200 family, the pooled hazard ratio (HR) was assessed. Heterogeneity among individual studies was also examined by subgroup analyses.ResultA total of 24 articles were included in the meta-analysis. The diagnostic value of miR-200s in BC was presented by the pooled sensitivity was 0.86 (95% CI: 0.83-0.88); the pooled specificity was 0.82 (95% CI: 0.72-0.89); the pooled AUC was 0.931 (95% CI: 0.919-0.942). Besides, expression of miR-200s in metastatic breast cancer has sensitivity, specificity and AUC of 0.70 (95%CI: 0.56-0.81), 0.72 (95%CI: 0.61-0.81), and 0.814 (95%CI: 0.741-0.903), respectively. The meta-analysis then revealed that high expression of miR-200 family corresponded to poor OS (HR: 1.63, 95% CI: 1.03-2.52), poor DFS (HR: 1.55, 95% CI: 0.95-2.56) in BC patients while downregulation of miRNA-200s corresponded to poor OS (HR= 0.84, 95%CI: 0.46-1.63) in TNBC patients and poor OS (HR=0.49; 95%CI: 0.27-0.88) in luminal BC patient.ConclusionThe MiR-200 family has high diagnostic accuracy and can be used as an important biomarker to prognosticate breast cancer.     

Efficacy and Safety of Radiotherapy Plus EGFR-TKIs in NSCLC Patients with Brain Metastases: A Meta-Analysis of Published Data

Background: The role of radiotherapy (RT) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains controversial. Therefore, we conducted a meta-analysis to comprehensively evaluate the efficacy and safety of RT plus EGFR-TKIs in those patients. Materials and Methods: Relevant literatures published between 2012 and 2017 were searched. Objective response rate(ORR), disease control rate (DCR), overall survival (OS), intracranial progression-free survival (I-PFS) and adverse events (AEs) were extracted. The combined hazard ratios (HRs) and relative risks (RRs) were calculated using random effects models. Results: Twenty-four studies (2810 patients) were included in the analysis. Overall, RT plus EGFR-TKIs had higher ORR (RR?=?1.32, 95%CI: 1.13–1.55), DCR (RR?=?1.12, 95%CI: 1.04–1.22), and longer OS (HR?=?0.72, 95%CI: 0.59–0.89), I-PFS (HR?=?0.64, 95%CI: 0.50–0.82) than monotherapy, although with higher overall AEs (20.2% vs 11.8%, RR?=?1.34, 95% CI: 1.11–1.62). Furthermore, subgroup analyses found concurrent RT plus EGFR-TKIs could prolong OS (HR?=?0.69, 95%CI: 0.55–0.86) and I-PFS (HR?=?0.57, 95%CI: 0.44–0.75). Asian ethnicity and lung adenocarcinoma (LAC) patients predicted a more favorable prognosis (HR?=?0.69,95%CI: 0.54–0.88, HR?=?0.66, 95%CI: 0.53–0.83, respectively). Conclusion: RT plus EGFR-TKIs had higher response rate, longer OS and I-PFS than monotherapy in NSCLC patients with BM. Asian LAC patients with EGFR mutation had a better prognosis with concurrent treatment. The AEs of RT plus EGFR-TKIs were tolerated.     

Prognostic Value of Epidermal Growth Factor Receptor Mutations in Resected Non-Small Cell Lung Cancer: A Systematic Review with Meta-Analysis

Background

The prognostic value of epidermal growth factor receptor (EGFR) mutations in resected non-small cell lung cancer (NSCLC) remains controversial. We performed a systematic review with meta-analysis to assess its role.

Methods

Studies were identified via an electronic search on PubMed, Embase and Cochrane Library databases. Pooled hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis.

Results

There were 16 evaluated studies (n = 3337) in the meta-analysis. The combined HR evaluating EGFR mutations on disease free survival was 0.96 (95% CI [0.79–1.16] P = 0.65). The combined HR evaluating EGFR mutations on overall survival was 0.86 (95% CI [0.72–1.04] P = 0.12). The subgroup analysis based on univariate and multivariate analyses in DFS and OS showed no statistically significant difference. There was also no statistically significant difference in DFS and OS of stage I NSCLC patients.

Conclusion

The systematic review with meta-analysis showed that EGFR mutations were not a prognostic factor in patients with surgically resected non-small cell lung cancer. Well designed prospective study is needed to confirm the result.     

Immediate Postmastectomy Breast Reconstruction Showed Limited Advantage in Patient Survival after Stratifying by Family Income

Background

Postmastectomy breast reconstruction is widely used in breast cancer patients for its aesthetic effect. Although several studies have casted suspicion upon the oncological safety of immediate breast reconstruction after mastectomy, the potential impact of different reconstruction methods on patient survival remains unclear.

Patients and Methods

We identified 35,126 female patients diagnosed with breast cancer from January 1, 1998 to December 31, 2002 in the Surveillance, Epidemiology, and End Results database. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients who underwent mastectomy with or without immediate breast reconstruction (autologous reconstruction or implant reconstruction) using Cox proportional hazard regression models.

Results

In multivariate analysis unadjusted for family income, patients undergoing immediate postmastectomy reconstruction exhibited improved BCSS [pooled reconstruction (any types of reconstruction): hazard ratio (HR)  =  0.87, 95% confidence interval (CI) 0.80–0.95, P = 0.001] and OS (pooled reconstruction: HR = 0.70, 95% CI 0.65–0.75, P<0.001) compared to patients who underwent mastectomy alone. However, after stratifying by family income, patients receiving reconstruction showed limited advantage in BCSS and OS compared with those undergoing mastectomy alone. When comparing between the two reconstruction methods, no significant differences were observed in either BCSS (implant versus autologous reconstruction: HR = 1.11, 95%CI 0.90–1.35, P = 0.330) or OS (implant versus autologous reconstruction: HR = 1.07, 95% 0.90–1.28, P = 0.424).

Conclusions

Compared to mastectomy alone, immediate postmastectomy reconstruction had limited advantage in survival after adjusting for confounding factor of family income. Our findings, if validated in other large databases, may help to illustrate the actual effect of immediate postmastectomy reconstruction on patient survival.     

Prognostic and clinical significance of focal adhesion kinase expression in breast cancer: A systematic review and meta-analysis

BackgroundThe prognostic significance of focal adhesion kinase (FAK) in breast cancer remains controversial. Here, we conducted a meta-analysis to explore the prognostic value of FAK expression in breast cancer.Materials and methodsPossible prognostic significance of protein or mRNA expression of FAK in breast cancer was investigated with searches of electronic databases for relevant publications. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted from eligible studies.ResultsA total of eight eligible studies which included 2604 participants were analyzed in this meta-analysis. Increased expression of FAK protein was found to significantly correlate with shorter overall survival (OS) (HR = 1.43, 95% CI: 1.12–1.83; P = 0.004), and not with disease-free survival (HR = 1.31, 95% CI: 0.92–1.85; P = 0.14). Elevated FAK protein expression was also associated with negative estrogen receptor (ER) expression (OR, 1.34; 95% CI, 1.06–1.68; P = 0.01), negative progesterone receptor (PR) expression (OR, 1.54; 95% CI, 1.22–1.93; P < 0.001), positive human epidermal growth factor receptor 2 (HER2) expression (OR, 1.64; 95% CI, 1.28–2.09; P < 0.001), triple-negative breast cancer (TNBC) (OR, 1.57; 95% CI, 1.14–2.17; P = 0.006), high nuclear grade (OR, 1.70; 95% CI, 1.05–2.78; P = 0.03), high Ki-67 expression level (OR, 2.87; 95% CI, 1.94–4.24; P < 0.001), and positive p53 status (OR, 2.28; 95% CI, 1.58–3.29; P < 0.001).ConclusionOur meta-analysis identifies an association between increased FAK protein expression and worse OS among breast cancer patients. Moreover, enhanced FAK expression is associated with negative ER expression, negative PR expression, positive HER2 expression, TNBC, high nuclear grade, high Ki-67 expression level, and positive p53 status in breast carcinoma.     

Toremifene and tamoxifen have similar efficacy in the treatment of patients with breast cancer: a meta-analysis of randomized trials

A meta-analysis of randomized trials was performed to compare the efficacy of toremifene (TOR) with tamoxifen (TAM) in patients with breast cancer. A total of 4,768 intention-to-treat patients from nine randomized trials were identified, with 2,587 patients in TOR group and 2,181 patients in TAM group. The primary outcomes were objective response rate (ORR), time to progression (TTP), and overall survival (OS). The ORR for TOR group was 26.2 % (303/1,156), whereas the ORR for TAM group was 25.2 % (284/1,128). The pooled RR suggested that the ORR were not statistically different between the two therapeutic groups (RR 1.04, 95 % CI 0.91–1.20, P = 0.57). The median TTP was 6.7 months for the TOR group and 9.7 months for the TAM group. The median OS was 30.1 months for the TOR group and 31.7 months for the TAM group. There were no significant difference in TTP and OS between two therapeutic groups (for TTP: HR 0.91, 95 % CI 0.82–1.00; for OS: HR 1.02, 95 % CI 0.91–1.15). Adverse events were generally similar in two therapeutic groups, but TOR may cause fewer vaginal bleeding (4.0 vs. 6.7 %, P < 0.01), headache (0.2 vs. 3.1 %, P = 0.02) and thromboembolic events (4.7 vs. 7.0 %, P = 0.04). Sensitivity analyses were performed by deleting a single study each time; all the results were not materially altered. In summary, the results of this meta-analysis suggest that TOR and TAM have similar efficacy in the treatment of patients with breast cancer.     

Association of Type 2 Diabetes Genetic Variants with Breast Cancer Survival among Chinese Women

ObjectiveTo evaluate whether the genetic susceptibility of T2D was associated with overall survival (OS) and disease-free survival (DFS) outcomes for breast cancer (BC).MethodsIncluded in the study were 6346 BC patients who participated in three population-based epidemiological studies of BC and were genotyped with either GWAS or Exome-chip. We constructed a genetic risk score (GRS) for diabetes using risk variants identified from the GWAS catalog (http://genome.gov/gwastudies) that were associated with T2D risk at a minimum significance level of P ≤ 5.0E-8 among Asian population and evaluated its associations with BC outcomes with Cox proportional hazards models.ResultsDuring a median follow-up of 8.08 years (range, 0.01–16.95 years), 1208 deaths were documented in 6346 BC patients. Overall, the diabetes GRS was not associated with OS and DFS. Analyses stratified by estrogen receptor status (ER) showed that the diabetes GRS was inversely associated with OS among women with ER- but not in women with ER+ breast cancer; the multivariable adjusted HR was 1.38 (95% CI: 1.05–1.82) when comparing the highest to the lowest GRS quartiles. The association of diabetes GRS with OS varied by diabetes status (P for interaction <0.01). In women with history of diabetes, higher diabetes GRS was significantly associated with worse OS, with HR of 2.22 (95% CI: 1.28–3.88) for the highest vs. lowest quartile, particularly among women with an ER- breast cancer, with corresponding HR being 4.59 (95% CI: 1.04–20.28). No significant association between the diabetes GRS and OS was observed across different BMI and PR groups.ConclusionsOur study suggested that genetic susceptibility of T2D was positively associated with total mortality among women with ER- breast cancer, particularly among subjects with a history of diabetes. Additional studies are warranted to verify the associations and elucidate the underlying biological mechanism.     

Overexpression of MMP Family Members Functions as Prognostic Biomarker for Breast Cancer Patients: A Systematic Review and Meta-Analysis

Background

Matrix metalloproteinases (MMPs) are regarded to be relevant to the prognosis of breast cancer. Numerous studies have confirmed the association between MMPs and tumor growth, invasion and metastasis in breast cancer. However, their prognostic values for survival in patients with breast cancer remain controversial. Hence, a meta-analysis was performed to clarify a more accurate estimation of the role of MMPs on prognosis of breast cancer patients.

Method

A systemic electronic search was conducted in PubMed, Embase and Web of science databases to identify eligible studies, which were associated with the relationship between MMPs and prognosis of breast cancer. The correlation in random-effect model was evaluated by using the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

A total of 28 studies covering 4944 patients were included for meta-analysis. A summary hazard ratio (HR) of all studies was calculated, as well as the sub-group HRs. The combined HRs calculated by either univariate or multivariate analysis both suggested that overexpression of MMPs had an unfavorable impact on overall survival (OS) (HR = 1.694, 95%CI: 1.347–2.129, P < 0.001; HR = 1.611, 95%CI: 1.419–1.830, P < 0.001, respectively). And the univariate analysis showed that patients with overexpression of MMPs had worse relapse-free survival (RFS) (HR = 1.969, 95%CI: 1.460–2.655, P < 0.001) in all eligible studies. In the sub-group analyses, HRs of MMP-9 positivity with poor OS were 1.794 (95%CI: 1.330–2.420, P < 0.001) and 1.709 (95%CI: 1.157–2.526, P = 0.007) which were separately evaluated by univariate and multivariate analysis. A small number of articles demonstrated that MMP-2 overexpression was not related with shorter OS (HR = 1.400, 95%CI: 0.610–3.029, P = 0.427). Four studies included in the OS analysis of MMPs expression in serum suggested that positive expression of serum MMPs may be an unfavorable factor (HR = 1.630, 95%CI: 1.065–2.494) for breast cancer patients. No publication bias was observed in the current meta-analysis.

Conclusions

Our findings suggested that MMPs overexpression (especially MMP-9, MMP-2, MMPs overexpression in serum) might indicate a higher risk of poor prognosis in breast cancer. Larger prospective studies are further needed to estimate the prognostic values of MMPs overexpression.     

Tumor Subtype-Specific Associations of Hormone-Related Reproductive Factors on Breast Cancer Survival

Purpose

It is inconclusive whether reproductive factors, which are known as risk factors of breast cancer, also influence survival. We investigated overall and subtype-specific associations between reproductive factors and breast cancer survival.

Methods

Among 3,430 incident breast cancer patients who enrolled in the Seoul Breast Cancer Study, 269 patients (7.8%) died and 528 patients (15.4%) recurred. The overall and subtype-specific associations of reproductive factors including age at menarche and menopause, duration of estrogen exposure, menstrual cycle, parity, age at first full-term pregnancy, number of children, age at last birth, time since the last birth, and duration of breastfeeding, on overall and disease-free survival (OS and DFS) were estimated by hazard ratios (HRs) and 95% confidence intervals (95% CIs) using a multivariate Cox proportional hazard model.

Results

An older age at menarche (HR for OS=1.10, 95% CI=1.03-1.19), a greater number of children (≥4 vs. 2, HR for DFS=1.58, 95% CI=1.11-2.26), and a shorter time since last birth (<5 vs. ≥20 years, HR for DFS=1.67, 95% CI=1.07-2.62) were associated with worse survival while longer duration of estrogen exposure with better survival (HR for DFS=0.97, 95% CI=0.96-0.99). In the stratified analyses by subtypes, those associations were more pronounced among women with hormone receptor and human epidermal growth factor 2 positive (HR+ HER2+) tumors.

Conclusions

It is suggested that reproductive factors, specifically age at menarche, number of children, time since last birth, and duration of estrogen exposure, could influence breast tumor progression, especially in the HR+ HER2+ subtype.     

The Prognostic Value of Forkhead Box P3 Expression in Operable Breast Cancer: A Large-Scale Meta-Analysis

Background

Recent studies have shown that the forkhead box P3 (FOXP3) protein has a prognostic role in breast cancer. However, these results are controversial. Therefore, the aim of this meta-analysis was to clarify the prognostic role of FOXP3 expression in operable breast cancer cases.

Methods

Eligible studies describing the use of FOXP3 as a prognostic factor for operable breast cancer cases were identified. Clinicopathological features, disease-free survival (DFS), and overall survival (OS) data were collected from these studies and were analyzed using Stata software.

Results

A total of 16 articles containing data from 13,217 breast cancer patients met the inclusion criteria established for this study. The subsequent meta-analysis that was performed showed that high levels of FOXP3 are not significantly associated with DFS and OS with significant heterogeneity. An additional subgroup analysis demonstrated that intratumoral FOXP3+ regulatory T cells (Tregs) were positively correlated with adverse clinicopathological parameters, yet they did not show an association with DFS or OS. For tumor cells, the pooled results revealed that FOXP3 is significantly associated with DFS (HR: 2.55, 95% CI: 1.23–5.30) but is not associated with clinicopathological parameters or OS. We also observed a significant correlation between FOXP3 expression and survival in the estrogen receptor-positive (ER)+ subgroup (HR: 1.83, 95% CI: 1.36–2.47 for DFS, HR: 1.87, 95% CI 1.28–2.73 for OS), in the Asian region (HR: 1.98, 95% CI: 1.56–2.50 for DFS, HR: 1.93, 95% CI: 1.12–3.35 for OS) and using the median as the FOXP3-positive cut-off value (HR: 1.94, 95% CI: 1.57–2.39 for DFS, HR: 2.06; 95% CI: 1.36–3.11 for OS).

Conclusion

This meta-analysis indicates that a prognostic role for FOXP3 expression in operable breast cancer cases depends on the FOXP3-positive region, ER status, geographic region and the FOXP3-positive cut-off value.     

Phase III Trials of Standard Chemotherapy with or without Bevacizumab for Ovarian Cancer: A Meta-Analysis

Background

Platinum-based standard chemotherapy improves survival of ovarian cancer (OC), but the five-year survival rate remains below 50%. Antiangiogenic agents (7.5 or 15 mg/kg Bevacizumab, Bev) plus to standard chemotherapy improve progression-free survival (PFS) not overall survival (OS) in completed randomized controlled trials (RCTs). The efficacy and safety of two doses of Bev + standard chemotherapy remain controversial.

Methods

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane databases and ClinicalTrials.gov were searched. The outcomes of eligible RCTs included PFS, OS and toxicities. Hazard ratio (HR) and relative risk (RR) were used for the meta-analysis and were expressed with 95% confidence intervals (CIs).

Results

Bev + chemotherapy improved PFS (HR, 0.82; 95% CI, 0.75 to 0.89; P = .000) and OS (HR, 0.87; 95% CI, 0.77 to 0.99; P = .026) in newly diagnosed OC (2 trials, 2776 patients), and PFS (HR, 0.48; 95% CI, 0.41 to 0.57; P = .000) in recurrent OC (2 trials, 845 patients). Bev + chemotherapy increased non-CNS bleeding (RR, 3.63; 95% CI, 1.81 to 7.29; P = .000), hypertension grade ≥ 2 (RR, 4.90; 95% CI, 3.83 to 6.25; P = .000), arterial thromboembolism (RR, 2.29; 95% CI, 1.33 to 3.94; P = .003), gastrointestinal perforation (RR, 2.90; 95% CI, 1.44 to 5.82; P = .003), and proteinuria grade ≥ 3 (RR, 6.63; 95% CI 3.17 to 13.88; P = .000). No difference was observed between the two Bev doses in PFS (HR, 1.04; 95% CI, 0.88 to 1.24) or OS (HR, 1.15, 95% CI, 0.88 to 1.50), but 15 mg/kg Bev increased toxicities.

Conclusion

Bev + standard chemotherapy delayed progression for newly diagnosed and recurrent OC, and improved survival for newly diagnosed OC. The 7.5 mg/kg dose appeared to be optimal for newly diagnosed OC patients with high risk for progression.     

Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis

Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07) and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS) to invasive cancer (OR=3.75; 95% CI, 1.8-7.78). Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43). Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.     

新辅助化疗后腋窝病理完全缓解乳腺癌的预后分析

摘要 目的：研究乳腺癌患者新辅助化疗（NAC）后达到腋窝淋巴结病理完全缓解（pathologic complete response of axillary,apCR）的远期生存以及影响远期生存的相关因素分析。方法：回顾性分析哈尔滨医科大学附属肿瘤医院乳腺外科624例乳腺癌患者的住院资料,采用Kaplan-Meier生存分析以及COX回归分析的统计学分析方法,分析乳腺癌患者新辅助化疗后腋窝状态与无病生存（DFS）和总生存（OS）的关系及影响apCR预后的因素。结果：apCR与非apCR患者比较DFS（P=0.013）和OS（P=0.037）差异具有统计学意义,apCR患者的预后与年龄、肿瘤大小、肿瘤受体状态、HER-2、ki67状态、分子分型等因素无相关性。结论：与非apCR患者相比,乳腺癌患者新辅助化疗后apCR患者预后更好,但apCR患者预后良好的因素仍需进一步临床试验分析。     

High-dose chemotherapy followed by autologous stem cell transplantation as a first-line therapy for high-risk primary breast cancer: a meta-analysis

Background and Objectives

Several trials have generated conflicting results about the results of high-dose chemotherapy followed by autologous stem cell transplantation (HDCT) for primary breast cancer. This meta-analysis summarizes the available evidence from all suitable studies.

Design and Methods

Prospective, randomized trials with HDCT as a first-line therapy for primary breast cancer were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival and overall survival); secondary endpoints included treatment-related mortality (TRM) and second (non-breast) cancers. We used a median age of 47, a PR positive rate of 50% and a premenopausal rate of 70% as cutoff values to complete the subgroup analyses, which were pre-planned according to the prepared protocol.

Results

Fourteen trials with 5747 patients were eligible for the meta-analysis. Compared with non-HDCT, non-significant second (non-breast) cancers (RR = 1.28; 95% CI = 0.82–1.98) and higher TRM (RR = 3.42; 95% CI = 1.32–8.86) were associated with HDCT for primary breast cancer. A significant DFS benefit of HDCT was documented (HR = 0.89; 95% CI = 0.79–0.99). No difference in OS (overall survival) was found when the studies were pooled (HR = 0.91; 95% CI = 0.82–1.00, p = 0.062). In subgroup analysis, age and hormone receptor status had a significant interaction with prolonged DFS and OS.

Conclusions

HDCT has a benefit on DFS and OS compared to SDC in some special patients with high-risk primary breast cancer.     

A Meta-Analysis of SMAD4 Immunohistochemistry as a Prognostic Marker in Colorectal Cancer

AIM: SMAD4 immunohistochemistry is considered a valuable prognostic marker in colorectal cancer, but individual studies have often been small and the results variable. A meta-analysis could potentially clarify these findings. METHODS: In September 2014, a Pubmed and Google Scholar search was conducted to find publications that reported the prognostic value of SMAD4 expression. A meta-analysis was performed to clarify the association between SMAD4 expression and survival outcomes. RESULTS: 137 studies were found, of which 13 were considered eligible. The studies consisted of a total of 3800 patients. Three different endpoints were taken into account, namely, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). In addition, the studies were divided into univariate and multivariate analyses. The pooled hazard ratios were given as follows: univariate CSS = 1.75 [95% confidence interval (CI): 0.93-3.32; z= 1.69; P= .09]; multivariate CSS = 2.17 (95% CI: 1.56-3.01; z= 4.65; P= .000); univariate DFS = 2.11 (95% CI: 1.36-3.28; z= 3.32; P= .001); multivariate DFS = 2.15 (95% CI: 1.56-3.01; z= 4.65; P= .000); univariate OS and DFS = 2.30 (95% CI: 1.41-3.73; z= 3.36; P= .001); univariate OS = 2.28 (95% CI: 1.30-4.00; z= 2.89; P= .004). CONCLUSION: The results of the presented meta-analyses indicate that SMAD4 expression status using immunohistochemistry is a prognostic marker for patient survival.     

SRC-1 and Twist1 Expression Positively Correlates with a Poor Prognosis in Human Breast Cancer

To evaluate the possible prognostic value of Steroid Receptor Coactivator-1 (SRC-1) and Twist1 expression in human breast cancer, we examined SRC-1 and Twist1 expression using immunohistochemistry on tissue microarray sections containing 137 breast cancer specimens. All patients were followed up for a median of 5 years following surgery. Survival curves were generated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazard regression model to assess the prognostic values. The results showed a positive correlation between SRC-1 and Twist1 expression at protein levels (P < 0.001). Also, SRC-1 expression positively correlated with HER2 expression (P = 0.024). The protein expression of Twist1 positively associated with lymph node metastasis (P < 0.001), but inversely correlated with PR status (P = 0.041). Patients with SRC-1 or Twist1-positive expression exhibited poorer overall survival (OS) and disease-free survival (DFS) than did those with SRC-1 or Twist1-negative expression (P < 0.05 for all). In addition, SRC-1-negativeive/Twist1-negative patients had the best OS and DFS (P < 0.01 for both). In multivariate survival analysis, SRC-1 expression, tumor stage, and PR were found to be independent prognostic factors related to OS (P = 0.019, < 0.001 and 0.02, respectively) and Twist1 expression, lymph node status and PR were independent predictors of DFS (P = 0.006, 0.001 and 0.029, respectively). These results suggest that a combined SRC-1/Twist1 expression status could improve the prognostic judgment for breast cancer patients.