Angiogenesis as a predictor of long-term survival for 377 Japanese patients with breast cancer

Angiogenesis, as assessed by microvessels, has been a common prognostic indicator for breast cancer in the last decade. However, the significance of angiogenesis remains controversial. This is a retrospective study of 377 Japanese patients selected from 663 breast cancer patients operated on between 1971 and 1987. To evaluate an objective method to quantify microvessel density in angiogenesis, we employed average microvessel count (AMC) per square millimeter. We investigated five factors: angiogenesis, lymph-node status (n), clinical tumor size (T), histological grade (HG), and tumor necrosis (TN), followed for a median of 10 years. Sixty-seven patients (17.8%) had recurrence and 54 patients (14.3%) died of breast cancer. Univariate analysis showed that n, T, HG, and AMC (P=0.0020) were significantly predictive of 20-year relapse-free survival (RFS). n, T, and HG were significantly associated with 20-year overall survival (OS) but AMC was borderline significant (P=0.0630). Multivariate analysis for RFS and OS showed that n, T, HG, and AMC (P<0.0001, P=0.0033, respectively) were all significant and independent prognostic factors. When stratified by T or n, a significant impact of AMC on RFS or OS was seen both in patients with T2 and T3 carcinomas or in node-negative patients, but not in T1 or node-positive patients. Thus, we can confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients, especially in node-negative patients and in patients with T2 and T3 carcinomas.     

Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer

This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c-erbB-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c-erbB-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1-20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c-erbB-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies.     

The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancer

This study was undertaken to examine the interaction between the combination of angiogenesis and blood vessel invasion (BVI) and haematogenous metastasis, and to determine the prognostic significance of that combination in predicting 20-year relapse-free survival (RFS) and overall survival (OS) rates in primary breast cancer. Five hundred and nine patients were studied. We investigated 11 factors, including average microvessel count (AMC)/BVI, lymph-node status (n), clinical tumour size (T), histological grade (HG), lymphatic vessel invasion (LVI), p53, proliferating cell nuclear antigen (PCNA), c-erbB-2, mitotic index (MI), apoptotic index, and tumour necrosis (TN). Blood vessel invasion was detected by both factor VIII-related antigen and elastica van Gieson staining. To evaluate the best objective method to quantify microvessel density in angiogenesis, AMC was employed. The rate of AMC-high and BVI-positive tumours was 32.6 and 29.3%, respectively. That of both AMC-high and BVI-positive tumours was 10.1%. Univariate analysis showed that AMC/BVI, n, T, HG, LVI, p53, PCNA, MI, and TN were significantly predictive of RFS and OS. By multivariate analysis, AMC/BVI was the strongest independent prognostic factor for 20-year RFS (relative risk (RR)=5.5; P<0.0001) and for 20-year OS (RR=4.3; P<0.0001). Lymph-node status was still considered a powerful prognostic indicator; however, the combination of AMC and BVI provided more reliable prognostic information than lymph-node status for haematogenous dissemination.     

New prognostic factors associated with long-term survival in node-negative breast cancer patients

Background  This study was undertaken to determine the absolute and relative value of angiogenesis, proliferating cell nuclear antigen (PCNA) and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Patients and Methods  Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including angiogenesis, PCNA using permanent-section immunohistochemistry, clinical tumor size, histological grade (HG), tumor necrosis, lymphatic vessel invasion (LVI), histological extension, histological classification, and infiltrating growth (INF), followed for a median of 10 years (range, 1 to 20). Results  Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that PCNA, clinical tumor size, HG, angiogenesis, and LVI were significantly predictive of 20-year RFS or OS. Tumor necrosis was significantly predictive of OS, not of RFS. Multivariate analysis showed that clinical tumor size (P=0.0003), angiogenesis (P=0.0003), PCNA (P= 0.0064), and HG (P=0.0401) were significant independent prognostic factors for RFS. PCNA (P< 0.0001) and clinical tumor size (P=0.0112) were significant independent prognostic factors for OS, while angiogenesis was a borderline significant factor. Conclusion  PCNA and angiogenesis were important new prognostic factors in node-negative breast cancer patients.     

Prognostic Significance of Carbonic Anhydrase IX (CA-IX), Endoglin (CD105) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in Breast Cancer Patients

The aim of this study was to examine the prognostic significance of carbonic anhydrase IX (CA-IX), an endogenous marker for tumor hypoxia; endoglin (CD105), a proliferation-associated and hypoxia-inducible glycoprotein and 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative DNA lesion, in breast cancer patients. Immunohistochemical expressions of CA-IX, CD105 and 8-OHdG, analyzed on paraffin-embedded tumor tissues from forty female breast cancer patients, were used to assess their prognostic implication on overall survival (OS) and relapse-free survival (RFS). Patients with high CA-IX expression (above cut-off value) had a higher occurrence of relapse (P = 0.002). High CA-IX expression was significantly associated with shorter RFS (P < 0.001, hazard ratio (HR) 0.21) and shorter OS (P < 0.001, HR 0.19). Lymph node negative patients with high CA-IX expression had worse RFS (P = 0.031, HR 0.14) and OS (P = 0.005, HR 0.05). Patients with grade I&II tumors and high CA-IX expression showed shorter RFS (P = 0.028, HR 0.28) and OS (P = 0.008, HR 0.20). Worse OS (P = 0.046, HR 0.28) was found in subgroup of patients with grade II tumors and high CA-IX expression. Among all three markers, only high CA-IX expression was strong independent prognostic indicator for shorter OS (HR 4.14, 95% CI 1.28–13.35, P = 0.018) and shorter RFS (HR 3.99, 95% CI 1.38–11.59, P = 0.011). Elevated expression of CA-IX was an independent prognostic factor for decreased RFS and OS and a significant marker for tumor aggressiveness. CD105 had week prognostic value; whereas, 8-OHdG, in this study, did not provide sufficient evidence as a prognostic indicator in breast cancer patients.     

Blood vessel invasion as a predictor of long-term survival for Japanese patients with breast cancer

A wide range of frequencies has been reported for blood vessel invasion (BVI) among patients with breast cancer, however, the prognostic significance of BVI remains controversial. Three hundred ninety-eight Japanese patients with breast cancer, operated on during the period between 1971 and 1987, were studied. We investigated five factors, including BVI, lymph-node status (n), clinical tumor size (T), histological grade (HG), and tumor necrosis (TN), followed for a median of 10years. BVI was detected by hematoxylin and eosin (HE) staining and both factor VIII-related antigen and elastica van Gieson staining. BVI detected by HE staining alone was defined as BVIh. The subtypes of BVI were classified as follows: BVI e, BVI detected only by elastica van Gieson staining; BVI f, BVI detected only by factor VIII-related antigen staining; and BVI e/f, BVI detected by both factor VIII-related antigen and elastica van Gieson staining. BVI-positive tumors were defined as lesions showing BVI e, BVI f, or BVI e/f. BVI and BVIh were presented in 27.4%, 6.5% of all cases, respectively. The mean diameters of the calibers of BVI e, BVI f, and BVI e/f were 141.9±80.5m, 61.0±37.4m, 136.0±102.0m, respectively (P < 0.0001). Seventy-three patients (18.3%) had recurrence and 60 patients (15.1%) died of breast cancer. Univariate analysis showed that BVIh (P<0.0001), BVI (P<0.0001), n, T, and HG were significantly predictive of 20-year RFS and OS. Multivariate analysis showed that BVI (P<0.0001, P=0.0088, respectively), n, T, and HG were all significant and independent prognostic factors for RFS and OS. On the other hand, BVIh was an independent factor for RFS (P= 0.0475), but of borderline significance for OS (P= 0.0506). When stratified by BVI, BVI e, and BVI e/f were significantly predictive of 20-year RFS or OS (P>0.0001). We can confirm BVI, especially BVI e and BVI e/f, are significant independent prognostic factors associated with long-term survival in Japanese breast cancer patients.     

Biological Characteristics and Long-term Outcomes in Node-negative Breast Cancer

BackgroundBecause the risk of relapse of node-negative breast cancer (BC) is varying, we evaluated the prognosis of patients with this disease and the factors associated with increased risk of relapse.Patients and MethodsThe clinical charts of patients with BC with evidence of negative nodes and with a potential ≥ 5-year follow-up were retrospectively reviewed.ResultsWe analyzed 1276 patients. Over a median follow-up of 71.6 months (range, 1-227.2 months), we observed 159 events of relapse or death. The median RFS was 170 months. The median overall survival (OS) was 192 months. At univariate analysis, older age, negative hormonal receptors, larger tumor size and higher proliferation index (Ki67) were associated with worse recurrence-free survival (RFS) and OS (P < .05); higher grading was associated with worse RFS (P = .01). At multivariate analysis for RFS, age, Ki67 and tumor size confirmed their independent prognostic role. At multivariate analysis for OS, age and positive hormonal receptors showed an independent prognostic role. We observed no differences in prognosis between human epidermal growth factor receptor 2 (HER2) positive and triple-negative (TN) BC, but TNBC showed a worse OS compared with luminal-like BC.ConclusionsIn node-negative BC, age, hormone receptor status, tumor size and Ki67 were prognostic factors. The TNBC subtype was not associated with poorer prognosis compared with the HER2-positive subtype, but showed a worse OS compared with luminal-like BC.     

Predictive and prognostic significance of cytoplasmic expression of ELAV-like protein HuR in invasive breast cancer treated with neoadjuvant chemotherapy

Cytoplasmic HuR is associated with reduced survival in invasive breast cancer. We designed this study to determine the predictive and prognostic value of HuR expression in women with breast cancer who underwent neoadjuvant chemotherapy followed by surgical resection. We immunohistochemically analyzed cytoplasmic HuR expression in tumor biopsy cores obtained from 139 patients with invasive breast cancers who received paclitaxel and anthracycline-based neoadjuvant chemotherapy. We evaluated the relationship of HuR expression level with pathologic complete response (pCR), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), recurrence-free survival (RFS), and overall survival (OS). Cytoplasmic HuR expression was present in 60 cases (43.2 %). The expression of cytoplasmic HuR was significantly associated with high nuclear grade (P < 0.0001) and ER (P = 0.001) and PR (P = 0.005) status. Multivariate regression analysis further revealed that high nuclear grade (P = 0.023), negative ER status (P = 0.043), and human epidermal growth factor receptor 2 (HER2) overexpression (P < 0.0001), but not cytoplasmic HuR expression, were significant independent predictors of pCR. Interestingly, multivariate Cox analysis revealed that cytoplasmic HuR expression was a strong independent predictor of reduced LRFS (P = 0.014), DRFS (P = 0.001), RFS (P < 0.0001), and OS (P = 0.019) irrespective of pCR. Furthermore, the patient group with tumors showing both expression of cytoplasmic HuR and non-pCR had a worse prognosis in LRFS (P = 0.048), DRFS (P < 0.0001), RFS (P < 0.0001), and OS (P = 0.001) than did other patient groups; patients with tumors showing negative cytoplasmic expression of HuR and pCR had the best prognosis in all RFS and OS. Cytoplasmic expression of HuR is an independent prognostic marker in breast cancer patients undergoing chemotherapy. Combination analyses of HuR expression and pCR, compared with pCR alone, can better predict clinical outcome in patients with primary breast cancer.     

Prognostic value of DNA ploidy in 653 Japanese women with node-negative breast cancer

Background. The prognostic value of DNA ploidy has been extensively studied in breast cancer; however, the results remain controversial. Flow cytometry (FCM) studies of DNA ploidy on frozen sections have not yet been performed in a large series of Japanese women with node-negative breast cancer. Methods. An FCM analysis of DNA ploidy was performed on frozen sections of node-negative breast cancer from 653 Japanese women, with a mean follow-up duration of 46 months. Results. Three hundred and twenty-four (49.6%) patients showed a diploid tumor, while 329 (50.4%) showed an aneuploid tumor. There was a significant correlation between DNA ploidy and estrogen receptor (ER) status. Patients with an aneuploid tumor had a significantly worse outcome in terms of both disease-free survival (DFS; P = 0.0116) and overall survival (OS; P = 0.0492) than those with a diploid tumor, while the same effect, in terms of DFS, was also seen in ER-positive breast cancer. Multivariate analyses indicated DNA ploidy to be an independent prognostic factor for DFS, while DNA ploidy and tumor size were found to be independent prognostic factors for OS. DNA ploidy was also shown to be an independent prognostic factor for DFS in ER-positive breast cancer. Conclusion. Our findings demonstrated DNA ploidy, based on FCM, to have an important prognostic value in Japanese women with node-negative breast cancer. Received: March 23, 2001 / Accepted: June 6, 2001     

Polyadenylate polymerase enzymatic activity in mammary tumor cytosols: A new independent prognostic marker in primary breast cancer

Polyadenylate polymerase (PAP) is one of the enzymes involved in the formation of the polyadenylate tail of the 3' end of mRNA. High levels of PAP activity were associated with rapidly proliferating cells. Here we evaluate the prognostic value of PAP activity in breast cancer patients. PAP specific activity values were measured by a highly sensitive assay in the tumor cytosols of 228 women with primary breast cancer. The median follow-up period was 58 months. PAP specific activity values ranged from 2.1-39.4 units/mg protein in the breast tumor cytosols, and the activity was correlated with the level of expression of the antigen. An optimal cutoff value of 5.5 units/mg extracted protein was first defined by statistical analysis. PAP status was then compared with other established prognostic factors in terms of relapse-free survival (RFS) and overall survival (OS). PAP activity levels had a tendency to increase with tumor-node-metastasis (TNM) stage and were higher in node-positive patients. Evaluation of the prognostic value of PAP was performed using univariate and multivariate analyses. Univariate analysis showed that PAP-positive patients had a less favorable prognosis for both RFS (relative risk (RR) = 2.35; P < 0.001] and OS (RR = 3.15; P < 0.001). PAP significantly added to the prognostic power for RFS (RR = 2.51; P = 0.0012) and OS (RR = 4.21; P < 0.001) in multivariate analysis, whereas patient age, tumor size, and nodal and ER status remained independent factors for predicting survival. When only node-negative patients were examined, PAP was found to be an independent factor for predicting RFS (RR = 3.68; P = 0.0032) and OS (RR = 4.81; P < 0.001). PAP did not appear to have a prognostic significance for node-positive patients. PAP is a new prognostic factor for early recurrence and death in breast cancer patients. Our results suggest that PAP may be used as an independent unfavorable prognostic factor in node-negative breast cancer patients because there were no significant associations between PAP and the other prognostic indicators evaluated in this group of patients.     

Nuclear IRS-1 predicts tamoxifen response in patients with early breast cancer

Insulin receptor substrate-1 (IRS-1) is a cytoplasmic scaffolding protein that is phosphorylated by insulin-like growth factor-I receptor and recruits downstream effectors. Recent evidence suggests that IRS-1 has a nuclear localization and function. Here we investigated whether nuclear and cytoplasmic IRS-1 levels are associated with clinico-pathological characteristics and clinical outcome in breast cancer patients. Tissue microarrays from 1,097 patients with stage I–II breast cancer were stained by immunohistochemistry for IRS-1. Nuclear and cytoplasmic IRS-1 were scored separately according to the Allred score. Nuclear IRS-1 showed a positive association with estrogen receptor (ER) (r = 0.09, P = 0.003) and progesterone receptor (PR) (r = 0.08, P = 0.008) status and a negative correlation with lymph node involvement (r = −0.10, P = 0.001). Cytoplasmic IRS-1 did not correlate with ER or PR but showed a positive correlation with tumor size (r = 0.10, P = 0.001) and S-phase fraction (r = 0.16, P < 0.001). In univariate analysis, tamoxifen-treated patients with tumors showing positive nuclear IRS-1 had a better recurrence-free survival (RFS) (P = 0.009) and overall survival (OS) (P = 0.0007), while no association was shown between cytoplasmic IRS-1 and RFS or OS in the same group of patients. In multivariate analysis of patients receiving tamoxifen, negative nuclear IRS-1 showed a significantly reduced RFS (P = 0.046) and OS (P = 0.018). Combining both PR and nuclear IRS-1, tamoxifen-treated patients with PR+/IRS-1+ tumors had a better RFS (P = 0.0003) and OS (P < 0.0001) when compared with patients with PR−/IRS-1− tumors. In conclusion, nuclear IRS-1 may be a useful marker to predict tamoxifen response in patients with early breast cancer, particularly when assessed in combination with PR.     

COX2 overexpression is a prognostic marker for Stage III breast cancer

To determine the significance of (Cyclooxygenase 2) COX2 for clinical outcome in breast cancer, we analyzed the correlation between COX2 overexpression and survival in 687 patients with invasive breast cancer. Cytoplasmic immunoreactivity of COX2 was determined as positive in 325 of 687 (47.3%) invasive breast cancers. COX2 positivity was significantly correlated with high histologic grade, negative estrogen receptor (ER), high Ki67, luminal B and triple-negative tumors, Bcl2 negativity, and p53 overexpression. In univariate analysis, COX2 overexpression resulted in significantly shorter relapse-free survival (RFS) [hazard ratio (HR) 1.487, 95% CI 1.035–2.110, P = 0.032]. Multivariate analysis revealed no significant association between COX2 overexpression and either overall survival (OS) or RFS. Kaplan–Meier analysis of the whole patient group showed significantly reduced RFS in patients with high COX2 expression, compared to those that did not overexpress COX2 (91 vs. 162 months, P = 0.031). Stratified subgroup analysis by TNM stage disclosed marked differences in OS and RFS rates in Stage III patients. We observed a significant association of COX2 overexpression with shorter RFS in the ER-negative subgroup of Stage III patients. The results show that COX2 overexpression is a significant unfavorable prognostic factor in Stage III breast cancer, and provide selective criteria for COX2 inhibitor combinations for invasive breast cancer therapy.     

Ep-CAM RNA expression predicts metastasis-free survival in three cohorts of untreated node-negative breast cancer

Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention as a prognostic factor in breast cancer. We aimed to validate the influence of Ep-CAM RNA expression in untreated node-negative breast cancer. Ep-CAM RNA expression was evaluated utilizing microarray-based gene-expression profiling in 194 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. The prognostic significance of Ep-CAM RNA expression for disease-free survival (DFS), metastasis-free survival (MFS), and breast cancer-specific overall survival (OS) was evaluated in univariate and multivariate analysis adjusted for age, grading, pTstage, ER as well as PR receptor and HER-2 status. Additionally, Ep-CAM RNA expression was compared with immunohistochemistry (IHC) for Ep-CAM in 194 patients. The prognostic impact of Ep-CAM gene expression was validated in further 588 node-negative breast cancer patients. Levels of Ep-CAM RNA expression showed a significant correlation with IHC (P = 0.001) and predicted in univariate analysis DFS (P = 0.001, HR = 2.4), MFS (P = 0.003, HR = 2.5), and OS (P = 0.002, HR = 3.1) accurately. The prognostic influence of Ep-CAM RNA was significant also in multivariate analysis for DFS (P = 0.017, HR = 2.0), MFS (P = 0.049, HR = 1.9), and OS (P = 0.042, HR = 2.3), respectively. The association with MFS was confirmed in an independent validation cohort in univariate (P = 0.006, HR = 1.9) and multivariate (P = 0.035, HR = 1.7) analysis. Ep-CAM RNA correlated with the proliferation metagene (P < 0.001, R=0.425) Nevertheless, in multivariate analysis, Ep-CAM was associated with MFS independent from the proliferation metagene (P = 0.030, HR = 1.8). In conclusion, Ep-CAM RNA expression is associated with poor MFS in three cohorts of untreated node-negative breast cancer.     

Tumor angiogenesis in breast cancer: Its importance as a prognostic indicator and the association with vascular endothelial growth factor expression

Summary The importance of tumor angiogenesis in the process of tumor growth and progression in solid tumors has been widely accepted. We have investigated the significance of tumor angiogenesis as a prognostic indicator in a retrospective study including 328 primary breast cancer patients. The postoperative survey demonstrated that the microvessel density (MVD) evaluated by immunocytochemical staining for factor VIII-related antigen is a potent prognostic indicator. The relapse-free survival (RFS) rate of patients with over 100 microvessels/mm² in a microscopic field was significantly worse compared to that of patients with less than 100 microvessels/mm² (p<0.00001). The significance of MVD was found in both node-negative and node-positve patients (p< 0.005 and p<0.01, respectively). Multivariate analysis confirmed that MVD is an independent prognostic indicator for RFS. In the background factor analysis, MVD was significantly correlated with the number of metastatic nodes (p<0.01). In addition, the immunocytochemical analysis for vascular endothelial growth factor (VEGF) demonstrated a close association between the increase in MVD and the expression of VEGF (p<0.001). VEGF status also was a significant prognostic indicator in univariate analysis for RFS (p<0.01). It was concluded that MVD is a potent prognostic indicator in primary breast cancer. Furthermore, it was also suggested that VEGF plays crucial roles in the promotion of angiogenesis in breast cancer.Abbreviations MVD microvessel density - VEGF vascular endothelial growth factor     

腋淋巴结阴性乳腺癌临床病理特征和预后的回顾性分析

目的:分析腋窝淋巴结阴性乳腺癌的临床病理特征及预后的影响因素。方法:收集215例腋窝淋巴结阴性及225例淋巴结阳性乳腺癌患者的临床病理及预后资料,应用χ2检验进行组间比较,以logistic回归进行多因素分析。结果:单因素分析显示,两组间月经状况(P=0.04)、肿瘤大小(P<0.001)、肿瘤分级(P=0.008)、肿瘤位置(P=0.001)差异均有统计学意义。多因素分析显示,肿瘤大小和肿瘤位置是影响淋巴结阴性和阳性乳腺癌患者独立的临床病理因素。两组预后指标分析显示,阴性组有较低的复发率(P<0.001)及远处转移率(P=0.002),有较高的术后生存率(P<0.001)。其中,肿瘤大小(P<0.001)、肿瘤分级(P=0.003)、肿瘤位置(P<0.001)是影响淋巴结阴性乳腺癌患者5年无病生存的因素;肿瘤大小(P=0.012)和肿瘤位置(P<0.001)是影响淋巴结阴性乳腺癌患者5年总生存的因素。结论:淋巴结阴性乳腺癌患者有较好的预后,肿块大小、肿瘤位置是淋巴结阴性乳腺癌患者的独立临床病理因素,也是影响淋巴结阴性乳腺癌患者5年无病生存率及总生存率的预后指标。     

Expression of Y-Box-binding protein 1 in Chinese patients with breast cancer

The purpose of this study was to investigate the expression of Y-Box-binding protein 1 (YB-1) in breast cancer and its correlation with clinicopathological characteristics and prognosis. Paraffin sections were retrospectively collected from 239 cases of stage I–III breast cancer patients and 30 healthy females who received surgery between January 2000 and December 2004 in the Chinese People’s Liberation Army General Hospital. The protein expression of YB-1 was detected by immunohistochemistry. The expression difference between the two groups and the correlation between YB-1 expression and clinicopathological characteristics and breast cancer prognosis were analyzed. Within the breast cancer group, YB-1 was expressed in the cytoplasm in 100.0% (239/239) of cases and in the nucleus in 36.8% (88/239) of cases. Within the control group of normal breast tissue, YB-1 was expressed in the cytoplasm in 100.0% (30/30) of cases and in the nucleus in 16.7% (5/30) of cases. The expression of YB-1 in the nucleus of breast cancer cells was significantly higher than that in normal breast tissue (P = 0.029). The expression of YB-1 in the nucleus of breast cancer cells positively correlated with the Scarff–Bloom–Richardson grade (P = 0.007) and HER-2 expression (P = 0.005), negatively correlated with ER expression (P = 0.004), and was independent of the age, menstrual status, pathological type, tumor size, lymph node status, presence of thrombosis, PR expression, and EGFR expression. The 5-year disease-free survival (DFS) and overall survival (OS) of patients with positive YB-1 expression in the nucleus were significantly lower than those of patients who were negative for nuclear YB-1 expression, and the difference was statistically significant (DFS 65.9% vs. 82.1%, P = 0.000; OS 79.5% vs. 92.1%, P = 0.000). Multivariate analysis suggested that the expression of YB-1 in the nucleus is an independent prognostic factor that affects DFS and OS in breast cancer patients (DFS P = 0.015; OS P = 0.035). In conclusion, the expression of YB-1 in the nucleus is related to carcinogenesis and the development of breast cancer. Therefore, YB-1 is an important molecular marker that can be used to predict breast cancer prognosis.     

The impact of adjuvant radiotherapy on the survival of primary breast cancer patients: a retrospective multicenter cohort study of 8935 subjects

BackgroundRadiotherapy (RT) is proven to be an important backbone for adjuvant therapy in randomized, controlled trials, but it is unclear if these effects are provable in a daily routine cohort of breast cancer patients. This study sought to answer the following questions in a daily routine cohort of breast cancer patients:1. Does guideline-adherent RT improve primary breast cancer patient survival?2. Is breast-conserving surgery (BCS) followed by RT equal to a mastectomy (MA) with regard to outcome parameters?3. Does adjuvant RT compensate for an incomplete tumor resection (R1)?Patients and methodsIn this retrospective, multicenter cohort study, we investigated data from 8935 primary breast cancer patients recruited from 17 participating certified breast cancer centers in Germany between 1992 and 2008. Guideline adherence based on internationally validated guidelines.ResultsThe patients who received guideline-adherent RT for primary breast cancer were associated with significantly improved survival parameters [recurrence-free survival (RFS): P < 0.001; overall survival (OS): P < 0.001] compared with patients who did not receive guideline-adherent adjuvant RT. Furthermore, the results demonstrated that there were no significant differences in RFS and OS between BCS followed by RT and MA [RFS: P = 0.293; OS: P = 0.104]. Adjuvant RT did not improve the outcome of patients receiving nonguideline-adherent incomplete tumor resection via BCS (R1); these patients showed a significantly impaired RFS [P < 0.001] and OS [P < 0.001] compared with patients who underwent guideline-adherent complete tumor resection via BCS (R0). In addition, non-guideline-adherent RT after MA (overtherapy) did not significantly influence survival [RFS: P = 0.838; OS: P = 0.613].ConclusionOur study confirms the importance of guideline-adherent adjuvant RT. It shows highly significant associations between RFS or OS and guideline adherent RT. Nevertheless, inadequate (R1-) surgical resection in a daily routine cohort of patients increases the risk of local recurrence and appears not to be compensated by the following RT.     

High expression of interleukin‐11 is an independent indicator of poor prognosis in clear‐cell renal cell carcinoma

Interleukin‐11 (IL‐11), a member of the IL‐6 family of cytokines, exerts pleiotropic oncogenic activities by stimulating angiogenesis and metastasis in many cancer types. The present study aims to evaluate the impact of IL‐11 expression on recurrence and mortality of patients with clear‐cell renal cell carcinoma (ccRCC). We retrospectively enrolled 193 ccRCC patients undergoing nephrectomy at a single center. Clinicopathologic features, recurrence‐free survival (RFS) and overall survival (OS) were recorded. IL‐11 intensity was assessed by immunohistochemistry in tumor specimens. The Kaplan–Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on RFS and OS. The concordance index (C‐index) was calculated to assess predictive accuracy. High IL‐11 expression is associated with increased risk of recurrence and poor survival for ccRCC patients (P < 0.001 and P < 0.001, respectively), especially those with early‐stage disease (TNM stage I + II). Multivariate analyses confirmed that IL‐11 expression was an independent prognostic factor for RFS and OS (P = 0.006 and P = 0.008, respectively). The predictive accuracy of well‐established prognostic models was improved when IL‐11 expression was integrated. In conclusion, high IL‐11 expression is an independent predictor of poor prognosis in ccRCC patients. It may help identify patients who could benefit from additional treatments and closer follow up.     

Prognostic value of tumor deposits in locally advanced rectal cancer: a retrospective study with propensity score matching

Background

The actual risks posed by tumor deposits (TDs) in colorectal cancer are still incompletely assessed. We explored the prognostic value of TDs in locally advanced rectal cancer (LARC) patients using propensity score matching (PSM) method.

Methods

Consecutive LARC patients in Peking University First Hospital between 2011 and 2015 were retrospectively analyzed. Kaplan–Meier methods and Cox proportional hazard regression analysis were conducted to explore prognostic values of TDs. PSM method was conducted to minimize selection bias. The correlation between TDs number and prognosis was explored.

Results

Four hundred and fifty-one LARC patients were recruited, and 78 (17.3%) patients were with TDs. Multivariate Cox analysis identified that the presence of TDs was an independent prognostic risk factor for overall survival (OS) (P?=?0.044). PSM identified 76 matched pairs of LARC patients, and Kaplan–Meier curves revealed that patients with TDs experienced worse  OS (log-rank P?=?0.0220) and relapse-free survival (RFS) (log-rank P?=?0.0117). Subgroup analysis of 50 pairs extracted by PSM from 246 LARC patients with lymph node metastasis (LNM) further proved that TDs were significantly associated with worse OS (log-rank P?=?0.0415), and the association was barely significant for RFS (log-rank P?=?0.0527). There were non-significant tendencies towards higher mortality in TDs?≥?2 than TD?=?1 group (log-rank P?=?0.348 for OS, log-rank P?=?0.087 for RFS).

Conclusion

Our study manifested that the presence of TDs was an independent risk factor for LARC patients. The prognostic value of TDs for LARC patients with LNM should not be ignored.

     

Clinical significance of axillary nodal ratio in stage II/III breast cancer treated with neoadjuvant chemotherapy

Purpose Neoadjuvant chemotherapy may modify the yield of involved axillary lymph nodes. The purpose of this study was to identify the clinical significance of the involved nodal ratios in patients with stage II/III breast cancer treated with neoadjuvant chemotherapy. Methods Two hundred and five stage II and III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. The patients received three cycles of neoadjuvant chemotherapy followed by curative surgery, either breast-conserving surgery or mastectomy with axillary lymph node dissection, and received three additional cycles of docetaxel/doxorubicin chemotherapy as adjuvant. Adjuvant radiotherapy and hormonal therapy were given after adjuvant chemotherapy when indicated. Results The median follow-up duration was 28.9 months. The overall response rate (RR) for neoadjuvant chemotherapy was 77.6%. The mean nodal ratio was 0.29 (range, 0–1.0; nodal ratio ≤0.25, 121 [59.0%] vs. >0.25, 84 [41.0%]). Relapse free survival (RFS) of the patients who had a nodal ratio >0.25 was significantly shorter (Hazard Ratio (HR) = 2.701, P = 0.001). A nodal ratio >0.25 was also associated with a shorter overall survival (OS) (HR = 4.109, P = 0.006). However, RFS and OS were not different according to the absolute number of involved nodes (ANIN) (P = 0.166, P = 0.248, respectively). In multivariate analysis, the nodal ratio was an independent prognostic factor for RFS and OS (HR = 4.246, P < 0.001; HR = 7.764, P < 0.001). Conclusion Axillary nodal ratios have an independent prognostic value in stage II/III breast cancer treated with neoadjuvant chemotherapy. Nodal ratio might be a useful tool to identify the patients at high risk of relapse in the neoadjuvant setting.