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1.
Nan Song Ji-Yeob Choi Hyuna Sung Sujee Jeon Seokang Chung Minkyo Song Sue K. Park Wonshik Han Jong Won Lee Mi Kyung Kim Keun-Young Yoo Sei-Hyun Ahn Dong-Young Noh Daehee Kang 《PloS one》2015,10(4)
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. 相似文献2.
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. 相似文献3.
Background
Despite the favorable prognosis for medullary breast cancer (MBC), the guidelines for the use of adjuvant chemotherapy for MBC have not been clearly established. This study investigated the prognostic role of adjuvant chemotherapy in Korean patients with node-negative (N0), triple-negative (TN) MBC patients.Methods
We included data from 252 patients with N0 TN MBC, obtained from the Korean Breast Cancer Registry database. Patients were categorized as those who did not undergo adjuvant chemotherapy (group I) or those who did (group II). Clinicopathological characteristics, breast cancer-specific survival (BCSS), and overall survival (OS) were compared between the groups. In addition, a subgroup analysis for survival based on tumor size was conducted.Results
A total of 252 N0 TN MBC patients with tumor sizes >1 cm who were diagnosed between April 1997 and March 2011 were enrolled. The median age was 44.95 years (range, 25–72 years), and the median follow-up period was 93.94 months (range, 23–195 months). Overall, the BCSS and OS in group II (97.3% and 97.3%, respectively) were significantly better compared with those in group I (89.2% and 86.2%, respectively). In the subgroup analysis, in patients with tumors >2 cm in size, those in group II had significant better BCSS and OS (97.5% and 97.5%, respectively) compared with those in group I (78.3% and 73.9%, respectively). In contrast in those with tumors 1–2 cm in size, there were no significant differences in BCSS and OS between the groups (both 97.1% for group I, and 95.2% and 92.9%, respectively for group II). Multivariate analysis revealed that adjuvant chemotherapy significantly improved BCSS (P = 0.009) and OS (P = 0.007), but only for patients with larger tumors (>2 cm).Conclusions
In patients with N0 TN MBC, adjuvant chemotherapy had a significant clinical survival benefit, but only in those with tumors >2 cm. 相似文献4.
Purpose
Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.Methods
Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.Results
Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.Conclusions
This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer. 相似文献5.
Marica Garziera Marcella Montico Ettore Bidoli Simona Scalone Roberto Sorio Giorgio Giorda Emilio Lucia Giuseppe Toffoli 《PloS one》2015,10(10)
Objective
Serum p53 autoantibodies (p53-AAbs) are the product of an endogenous immune response against p53 overexpression driven by the ovarian tumour. The p53-AAbs are detectable only in a subset of patients. To date, the evidence of an association between the presence of p53-AAbs and ovarian cancer outcomes has been poorly investigated.Methods
A systematic literature search was performed to identify eligible studies investigating the association of serum p53-AAbs and overall survival (OS) and disease free survival (DFS). Associations between presence of serum p53-AAbs and baseline tumour characteristics were also evaluated. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed to estimate the prognostic impact of serum p53-AAbs. Heterogeneity between studies was assessed.Results
A total of 583 patients (7 studies) for OS and 356 patients (4 studies) for DFS were included in the meta-analysis. Presence of p53-AAbs was not associated to OS (pooled uni- multivariate HR = 1.09; 95% CI: 0.55–2.16), and a large heterogeneity was found. When only multivariate HRs were pooled together (4 studies), presence of p53-AAbs was significantly associated to a better OS (pooled HR = 0.57; 95% CI: 0.40–0.81), and no significant heterogeneity was observed. A reduced DFS was associated to p53-AAbs (pooled uni- multivariate HR = 1.37; 95% CI: 0.83–2.25), though not significantly and with a moderate heterogeneity.Conclusions
The prognostic significance of serum p53-AAbs in ovarian cancer was diverging according to uni or multivariate models used. Since the results of this work were based on only few investigations, large prospective studies are needed to better define the role of antibody immunity against p53. 相似文献6.
Sofia Agelaki Antonia Kalykaki Harris Markomanolaki Maria A. Papadaki Galatea Kallergi Dora Hatzidaki Kostas Kalbakis Dimitrios Mavroudis Vassilis Georgoulias 《PloS one》2015,10(6)
Background
To evaluate the efficacy of lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor, in therapy-resistant HER2-positive CTCs in metastatic breast cancer (MBC).Patients and Methods
Patients with MBC and HER2-positive CTCs despite disease stabilization or response to prior therapy, received lapatinib 1500 mg daily in monthly cycles, till disease progression or CTC increase. CTC monitoring was performed by immunofluorescent microscopy using cytospins of peripheral blood mononuclear cells (PBMCs) double stained for HER2 or EGFR and cytokeratin.Results
A total of 120 cycles were administered in 22 patients; median age was 62.5 years, 15 (68.2%) patients were post-menopausal and 20 (90.1%) had HER2-negative primary tumors. At the end of the second course, HER2-positive CTC counts decreased in 76.2% of patients; the median number of HER2-positive CTCs/patient also declined significantly (p = 0.013), however the decrease was significant only among patients presenting disease stabilization (p = 0.018) but not among those with disease progression during lapatinib treatment. No objective responses were observed. All CTC-positive patients harbored EGFR-positive CTCs on progression compared to 62.5% at baseline (p = 0.054). The ratio of EGFR-positive CTCs/total CTCs detected in all patients increased from 17.1% at baseline to 37.6% on progression, whereas the mean percentage of HER2-negative CTCs/patient increased from 2.4% to 30.6% (p = 0.03).Conclusions
The above results indicate that lapatinib is effective in decreasing HER2-positive CTCs in patients with MBC irrespectively of the HER2 status of the primary tumor and imply the feasibility of monitoring the molecular changes on CTCs during treatment with targeted agents.Trial Registration
Clinical trial.gov NCT00694252 相似文献7.
Nan Song Ji-Yeob Choi Hyuna Sung Sujee Jeon Seokang Chung Sue K. Park Wonshik Han Jong Won Lee Mi Kyung Kim Ji-Young Lee Keun-Young Yoo Bok-Ghee Han Sei-Hyun Ahn Dong-Young Noh Daehee Kang 《PloS one》2015,10(4)
Purpose
To identify the genetic variants associated with breast cancer survival, a genome-wide association study (GWAS) was conducted of Korean breast cancer patients.Methods
From the Seoul Breast Cancer Study (SEBCS), 3,226 patients with breast cancer (1,732 in the discovery and 1,494 in the replication set) were included in a two-stage GWAS on disease-free survival (DFS) by tumor subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). The associations of the re-classified combined prognostic markers through recursive partitioning analysis (RPA) of DFS for breast cancer were assessed with the Cox proportional hazard model. The prognostic predictive values of the clinical and genetic models were evaluated by Harrell’s C.Results
In the two-stage GWAS stratified by tumor subtypes, rs166870 and rs10825036 were consistently associated with DFS in the HR+ HER2- and HR- HER2- breast cancer subtypes, respectively (P rs166870=2.88×10-7 and P rs10825036=3.54×10-7 in the combined set). When patients were classified by the RPA in each subtype, genetic factors contributed significantly to differentiating the high risk group associated with DFS inbreast cancer, specifically the HR+ HER2- (P discovery=1.18×10-8 and P replication=2.08×10-5) and HR- HRE2- subtypes (P discovery=2.35×10-4 and P replication=2.60×10-2). The inclusion of the SNPs tended to improve the performance of the prognostic models consisting of age, TNM stage and tumor subtypes based on ER, PR, and HER2 status.Conclusion
Combined prognostic markers that include clinical and genetic factors by tumor subtypes could improve the prediction of survival in breast cancer. 相似文献8.
Background
Anemia related to adjuvant chemotherapy might predict compromised survival in patients with breast cancer. The present population-based study was to investigate the correlation of pretreatment anemia with pathological response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy (NCT).Methods
From 1999 to 2011, a total of 655 patients with operable or locally advanced breast cancer who underwent NCT before definitive surgery were reviewed. The patients were subdivided into anemic (baseline hemoglobin (Hb)<12.0g/dL) and non-anemic (Hb≥12.0g/dL) groups. Comparison was made between anemic and non-anemic groups concerning the rate of pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS). Logistic and Cox regression models were utilized to determine the predictive value of pretreatment anemia in outcomes of patients undergoing NCT.Results
166 women (25.3%) were anemic before treatment. Patients in the anemic group were less likely to achieve pCR in NCT than their non-anemic counterparts (odds ratio (OR) 0.428, 95% confidence interval (CI) 0.198–0.927, p = 0.031). Patients with baseline anemia displayed inferior 10-year RFS (59.1% vs 66.0%, p = 0.022 by log-rank), OS (75.3% vs 90.9%, p<0.001) and CSS (82.4% vs 94.4%, p<0.001) compared with those without. After adjustment for confounders, pretreatment anemia was demonstrated to correlate with elevated risk of relapse (hazard ratio (HR) 1.453, 95% CI 1.077–1.962, p = 0.015), cancer-specific mortality (HR 2.961, 95% CI 1.679–5.222, p<0.001) and all-cause mortality (HR 2.873, 95% CI 1.757–4.699, p<0.001).Conclusions
Pretreatment anemia was associated with worse pathological response to NCT as well as survival status in breast cancer. Further studies are warranted to identify optimal interventions and improve the prognosis of this subgroup. 相似文献9.
Purpose
Nucleolar spindle-associated protein (NuSAP1) is an important mitosis-related protein, and aberrant NuSAP1 expression is associated with abnormal spindles and mitosis. This study investigated the prognostic value of NuSAP1 in breast cancer.Methods
Two sets of tissue microarrays (TMAs) that included samples from 450 breast cancer patients were constructed, of which 250 patients were training set and the other 200 patients were validation set. Immunohistochemical staining was performed to determine the NuSAP1 levels. A Kaplan-Meier analysis was used to estimate the prognostic value of NuSAP1 in breast cancer. A stepwise Cox analysis was performed to construct a risk-prediction model for triple-negative breast cancer (TNBC). All statistical analysis was performed with SPSS software.Results
There were 108 (43.5%) and 88 (44.0%) patients expressed NuSAP1 in the training set and validation set respectively. High levels of NuSAP1 expression were related to poor disease-free survival (DFS) in both training (P = 0.028) and validation (P = 0.006) cohorts, particularly in TNBC. With combination of two cohorts, both NuSAP1 (HR = 4.136, 95% CI: 1.956–8.747, P < 0.001) and BRCA1 (HR = 0.383, 95% CI: 0.160–0.915, P = 0.031) were independent prognostic indicators of DFS in TNBC. A receiver operating characteristic (ROC) analysis revealed that the combination of NuSAP1 and BRCA1 significantly improved the prognostic power compared with the traditional model (0.778 versus 0.612, P < 0.001).Conclusions
Our study confirms the prognostic value of NuSAP1 in breast cancer. The combination of NuSAP1 and BRCA1 could improve the DFS prediction accuracy in TNBC. 相似文献10.
Objectives
The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.Methods
We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients).Results
The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0–1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.Conclusions
PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes. 相似文献11.
Taeryool Koo Changhoon Song Jae-Sung Kim Kyubo Kim Eui Kyu Chie Sung-Bum Kang Keun-Wook Lee Jee Hyun Kim Seung-Yong Jeong Tae-You Kim 《PloS one》2015,10(9)
Purpose
To evaluate the prognostic impact of the lymph node ratio (LNR) in ypStage III rectal cancer patients who were treated with neoadjuvant chemoradiotherapy (NCRT).Materials and Methods
We retrospectively reviewed the data of 638 consecutive patients who underwent NCRT followed by total mesorectal excision, and postoperative adjuvant chemotherapy for rectal cancer from 2004 to 2011. Of these, 125 patients were positive for lymph node (LN) metastasis and were analyzed in this study.Results
The median numbers of examined and metastatic LNs were 17 and 2, respectively, and the median LNR was 0.143 (range, 0.02–1). Median follow-up time was 55 months. In multivariate analyses, LNR was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] 2.17, p = 0.041), disease-free survival (DFS) (HR 2.28, p = 0.005), and distant metastasis-free survival (DMFS) (HR 2.30, p = 0.010). When ypN1 patients were divided into low (low LNR ypN1 group) and high LNR (high LNR ypN1 group) according to a cut-off value of 0.152, the high LNR ypN1 group had poorer OS (p = 0.043) and DFS (p = 0.056) compared with the low LNR ypN1 group. And there were no differences between the high LNR ypN1 group and the ypN2 group in terms of the OS (p = 0.703) and DFS (p = 0.831).Conclusions
For ypN-positive rectal cancer patients, the LNR was a more effective prognostic marker than the ypN stage, circumferential resection margin, or tumor regression grade after NCRT, and could be used to discern the high-risk group among ypN1 patients. 相似文献12.
Fanghui Ren Ruixue Tang Xin Zhang Wickramaarachchi Mihiranganee Madushi Dianzhong Luo Yiwu Dang Zuyun Li Kanglai Wei Gang Chen 《PloS one》2015,10(8)
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. 相似文献13.
Ji Yun Lee Sung Hee Lim Min-Young Lee Hae Su Kim Jin Seok Ahn Young-Hyuck Im Yeon Hee Park 《PloS one》2016,11(2)
Background
Metastatic breast cancer (MBC) remains a devastating and incurable disease. Over the past decade, the implementation of clinical trials both with and without molecular targeted therapeutics has impacted the daily clinical treatment of patients with MBC. In this study, we determine whether including MBC patients in clinical trials affects clinical outcomes.Methods
We retrospectively reviewed data for a total of 863 patients diagnosed with initial or recurrent (after receiving adjuvant systemic treatments following surgery) metastatic disease between January 2000 and December 2013. Data were obtained from the breast cancer database of Samsung Medical Center.Results
Among the 806 patients selected for inclusion, 188 (23%) had participated in clinical trials. A total of 185 clinical trials were conducted from 2000 to 2014. When compared with earlier periods (n = 10 for 2000–2004), clinical trial enrollment significantly increased over time (n = 103 for 2005–2009, P = 0.024; n = 110 for 2010–2014, P = 0.046). Multivariate analyses revealed that biologic subtype, distant recurrence free interval (DRFI), and clinical trial enrollment were independent predictors of overall survival. Patients who participated in clinical trials showed improved survival, with a hazard ratio of 0.75 (95% CI, 0.59–0.95), which was associated with a 25% reduction in the risk of death. However, subgroup analysis showed that this improved survival benefit was not maintained in patients with triple negative breast cancer (TNBC).Conclusions
Although not conclusive, we could speculate that there were differences in the use of newer agents or regimens over time, and these differences appear to be associated with improved survival. 相似文献14.
KK Chan B Dassanayake R Deen RE Wickramarachchi SK Kumarage S Samita KI Deen 《World journal of surgical oncology》2010,8(1):1-11
Introduction
Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints.Methods
75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).Results
Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07).Conclusion
Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future. 相似文献15.
Zonglin Chen Aslihan Gerhold-Ay Susanne Gebhard Daniel Boehm Christine Solbach Antje Lebrecht Marco Battista Isabel Sicking Christina Cotarelo Cristina Cadenas Rosemarie Marchan Joanna D. Stewart Mathias Gehrmann Heinz Koelbl Jan G. Hengstler Marcus Schmidt 《PloS one》2012,7(9)
Background
Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzed the association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients.Material and Methods
IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status.Results
160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantly associated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360–0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233–0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315–0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196–0.705).Conclusion
Expression of IGKC has an independent protective impact on DFS and OS in node-negative breast cancer. 相似文献16.
Fabien Vidal Paul Guerby Mathieu Luyckx Pascale Haddad Eberhard Stoeckle Philippe Morice Eric Leblanc Fabrice Lecuru Emile Dara? Jean Marc Classe Christophe Pomel Thomas Filleron Gwenael Ferron Denis Querleu Arash Rafii 《PloS one》2016,11(1)
Objective
Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients.Study Design
We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis.Results
The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5).Conclusion
ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters. 相似文献17.
Purpose
Breast cancer remains a major cause of death in women worldwide, and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment. Chronic inflammation is often related to the occurrence and growth of various malignancies. This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response: myeloid differentiation primary response 88 (MyD88) and Toll-like receptor 4 (TLR4).Methods
We analyzed data from 205 breast invasive ductal carcinoma (IDC) patients who were treated at the Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, from 2002 to 2006. Overall survival (OS) and disease-free survival (DFS) were compared.Results
In total, 152 patients (74.15%) were disease-free without relapse or metastasis, whereas 53 (25.85%) patients developed recurrence or metastasis. A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001). Patients with high expression were more likely to experience death and recurrence/metastasis events (p<0.05). Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels (log-rank test: p<0.001). Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test: p<0.001). In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663–6.641; p = 0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546–13.098; p = 0.006).Conclusions
TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer. Therefore, TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy. 相似文献18.
Background
Studies have indicated that statins influence the risks and mortality rates of several types of solid tumors. However, the association between statin use and survival in patients with colorectal cancer (CRC) remains unclear.Methods
We searched the PubMed and Embase databases for relevant studies published up to September 2014 that assessed statin use and CRC prognosis. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). The secondary outcomes were disease-free survival (DFS) and recurrence-free survival (RFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled with Mantel–Haenszel random-effect modeling. All statistical tests were two-sided.Results
Four studies on post-diagnosis statin therapy and five studies on pre-diagnosis statin use were included in our meta-analysis of 70,608 patients. Compared with the non-users, the patients with post-diagnosis statin use gained survival benefits for OS (HR 0.76; 95% CI: 0.68 to 0.85, P<0.001) and CSS (HR 0.70; 95% CI: 0.60 to 0.81, P<0.001). In addition, we observed that pre-diagnosis statin use prolonged the survival of patients with CRC for OS (HR 0.70; 95% CI: 0.54 to 0.91, P=0.007) and CSS (HR 0.80; 95% CI: 0.74 to 0.86, P<0.001). However, we did not observe a survival benefit for DFS (HR 1.13; 95% CI: 0.78 to 1.62, P=0.514) or RFS (HR 0.98; 95% CI: 0.36 to 2.70, P=0.975) in the CRC patients with post-diagnosis statin use.Conclusions
Statin use before or after cancer diagnosis is related to reductions in overall and cancer-specific mortality in colorectal cancer survivors. 相似文献19.
Background
Breast cancer survivors have an increased risk of bone fracture. But the risk among young patients with adjuvant therapies remains unknown. This population-based study is aimed to assess the incidence and risk of fracture among young (age of 20 to 39 years) breast cancer patients who received adjuvant therapies.Methods
From January 2001 to December 2007, 5,146 newly diagnosed breast cancer patients were enrolled from the National Health Insurance Research Database (NHIRD) in Taiwan. Patients were observed for a maximum of 6 years to determine the incidence of newly onset fracture. Kaplan Meier and Cox regression analyses were used to evaluate the risk of fracture in young breast cancer patients who received adjuvant treatments.Results
Of the total 5,146 young (age of 20 to 39 years) breast cancer patients, the Cox multivariate proportional hazards analysis showed that AIs, radiotherapy, and monoclonal antibodies were significantly associated with a high risk of fracture. Moreover, patients who received AIs for more than 180 days had a high hazard ratio (HR) of 1.77 (95% CI = 0.68–4.57), and patients who received more than four radiotherapy visits had a high HR of 2.54 (95% CI = 1.07–6.06). Under the site-specific analysis, young breast cancer patients who received AIs had the highest risk of hip fracture (HR = 8.520, 95% CI = 1.711–42.432, p < 0.04), whereas patients who received radiotherapy had the highest risk of vertebral fracture (HR = 5.512, 95% CI = 1.847–16.451, p < 0.01).Conclusion
Young breast cancer patients who are receiving AIs, radiotherapy or monoclonal antibody need to be more careful for preventing fracture events. Breast cancer treatment plans are suggested to incorporate fracture prevention interventions. 相似文献20.