Abstract HECT domain E3 ubiquitin ligase 1 (HECTD1) has been reported to be a negative regulator of epithelial-mesenchymal transition and to decrease breast cancer invasion and metastasis. However, the clinical significance and detailed role of HECTD1 in breast cancer remain elusive. We investigated the role of HECTD1 in two large breast cancer cohorts using mRNA and protein expression, and bioinformatics. We examined the prognostic significance of HECTD1 by multivariate analysis. HECTD1 mRNA expression (HECTD1 expression) was lower in breast cancer compared with adjacent normal tissues. HECTD1 expression levels also differed among breast cancer subtypes. Decreased HECTD1 expression was significantly associated with aggressive tumour characteristics, including large tumour size and high histological grade. HECTD1 expression was inversely associated with mitochondrial cellular respiratory function and reactive oxygen species in breast cancer tissues. Multivariate analysis identified low HECTD1 mRNA expression level as an independent risk factor for disease-free ( P = 0.009) and overall ( P = 0.046) survival among breast cancer patients. There was no association of HECTD1 protein expression with mRNA expression and prognosis. HECTD1 mRNA expression is a candidate prognostic biomarker in breast cancer. The poor prognosis of patients with low HECTD1 mRNA expression may be associated with increased mitochondrial respiratory function.
10609 Background: Skp2 (S-phase kinase-associated protein 2) is substrate-recognizing subunit of an ubiquitin E3 ligase SCF (Skp1, Cullin and F-box) complex and has a major role in p27 regulation. Overexpression of Skp2 is frequently seen in human tumors, often correlating with poor prognosis. Anaphase-promoting complex/cyclosome (APC/C) is another most prominent ubiquitin E3 ligase in cell cycle control, and its function is tightly controlled by activating subunit Cdh1 (Fizzy-related). APC-Cdh1 complex is supposed to be involved in Skp2 proteolysis and have essential role for S phase entry, however clinical significance of Cdh1 have not evaluated yet. Herein we examined the significance of Cdh1 in breast cancer. Methods: Firstly, MCF7 human breast cancer cells and MCF10A normal breast epithelial cells were analyzed in vitro and in vivo. Thereafter, using tissue microarray, we evaluate the expression profile of Cdh1, Skp2 and p27 in both breast cancer and normal breast epithelial tissue. Moreover, clinicopathological significance (age, tumor size, lymph node metastasis, distant metastasis, histological grade, and stage) of Cdh1 was analyzed from 126 breast cancer patients. Chi square-test, Fisher's exact test were used for statistical analysis of immunostaining results and clinicopathological data. p<0.05 was considered statistically significant. Results: Overexpression of Cdh1 induced attenuation of Skp2 and increased p27 protein expression, resulted in growth suppression. Moreover, knockdown of Cdh1 promoted higher Skp2 expression and S-phase population, reduced p27 and consequently induced cell transformation and proliferation in vitro and in vivo. Tissue microarray results appeared that positive Cdh1 and p27 was more frequently seen in normal breast tissue and statistically significant. On the other hand, Skp2 was less in normal tissue. Furthermore, Cdh1 positive breast cancer was more frequently seen in low histological grade tumors and statistically significant (p=0.04). Conclusions: Skp2 protein expression is regulated by Cdh1 in breast cancer. Cdh1 expression could be possible novel biomarker in patient with breast cancer. No significant financial relationships to disclose.
It is well known that many subjects who survived a suicide attempt will make further suicide attempts, even after the medical treatment at critical emergency unit. To examine the effectiveness of continuous follow-up care by case manager after the suicide attempt, a randomized, controlled, multicenter trial by J-MISP (Japanese Multimodal Intervention Trials for Suicide Prevention) has been launched in 2005. This research project is one of the strategic research projects funded by The Japanese Ministry of Health, Labour and Welfare. In this study, J-MISP will implement the intervention for suicide attempters, a considerably high-risk group of further suicide attempts, who are transported by emergency services. After a brief psychoeducation, the study subjects will be randomly assigned to continuous case management group or standard care group as a control. The subjects will be followed up for 1.5 to 3.5 years. The primary outcome measure is the reduction of the number of further suicide. Suicide ideation, depressive symptoms, and general health condition will be also evaluated as secondary measures. We hope that the results of this trial will help to develop effective strategies to prevent further suicide attempts in Japan. Language: en
Abstract Purpose: Although chronic postsurgical pain (CPSP) after breast cancer surgery is a common and prevalent postsurgical adverse event, the need for CPSP treatment has not been investigated. This study examined the proportion of patients who needed treatment for CPSP and associated predictors. Methods: We conducted a cross-sectional study with female patients who underwent breast cancer surgery at our institution. Participants were aged ≤65 years at the time of this study and were at least 1 year post surgery. The questionnaire examined the presence of and need for treatment for CPSP and included the Japanese version of the Concerns about Recurrence Scale (CARS-J). Multivariate analyses were used to identify independent predictors of needing treatment for CPSP. Results: In total, 305 patients completed the questionnaire. The mean time since surgery was 67.1 months; 151 (51%) patients developed CPSP after breast cancer surgery and 61 (39%) needed treatment for CPSP. Among patients that developed CPSP, the fear of breast cancer recurrence as assessed by the CARS-J (odds ratio [OR] 2.22, 95% confidence interval [CI]: 1.30–3.81, P =0.004) and > 2 postsurgical pain regions (OR 2.52, 95% CI: 1.16–5.57, P=0.020) were independent predictors of needing treatment for CPSP. Conclusions: This study is the first to identify the proportion and predictors of patients who need treatment for CPSP. Fear of breast cancer recurrence and > 2 postsurgical pain regions may predict the need for CPSP treatment among patients following breast cancer surgery.
Fulvestrant, a pure estrogen receptor antagonist with no known agonist effects, was approved in September 2011 for the treatment of hormone-receptor positive metastatic breast cancer(MBC)in postmenopausal women in Japan. Here, we present a retrospective review of data from 73 heavily pretreated patients who received a high-dose regimen of fulvestrant in our hospital. Patients received a median of 3 endocrine therapies(range: 1-7)prior to the fulvestrant regimen. Partial response was observed in 4 patients, and 10 patients experienced stable disease for more than 6 months(objective response rate: 5.5%; clinical benefit rate: 19.2%). The median time to progression was 2.8 months. Fulvestrant was well tolerated; however, Grade 3 neuropathy at the injection site was observed in 2 patients. Of 12 patients, 3 responded to endocrine therapy following fulvestrant treatment. Our clinical experience indicates that fulvestrant can be administered to patients pretreated with several lines of endocrine therapy, although its efficacy as first- or second-line endocrine therapy has been demonstrated in clinical trial settings.
Introduction: Breast adenomyoepithelioma (AME) is a rare tumor composed of myoepithelial cells and ductal or luminal cells. Most cases of AME are benign, but rare cases in which either or both cell types exhibited malignant features have been reported. Due to its rarity, no diagnostic criteria for malignancy have been established for AME. Patient concerns: A 64-year-old woman presented with a mass in her right breast. Fine-needle aspiration cytology and biopsy examinations revealed lesions composed of spindle-shaped cells and round epithelial cells. AME was suspected, and partial mastectomy was performed. Diagnosis: The tumor specimen showed AME, which mainly consisted of spindle-shaped myoepithelial cells with slight atypia, admixed with tubular luminal cells and small areas of atypical intraductal proliferative lesions. No apparent features of malignancy, such as necrosis or invasion, were seen in the myoepithelial cells or the luminal or intraductal component. However, the atypical intraductal component exhibited focal nuclear atypia, a cribriform pattern, and moderate to strong membranous human epidermal growth factor receptor 2 (HER2) immunoreactivity. HER2 amplification was detected in focal regions of the atypical intraductal component by fluorescence in situ hybridization (FISH), which resulted in a diagnosis of AME with ductal carcinoma in situ. Outcomes: The patient did not receive further therapy and was free from tumor recurrence at 23 months after the operation. Conclusion: HER2 FISH might be useful for evaluating suspected AME tumors for malignancy when an atypical ductal lesion that lacks definitive features of malignancy is encountered.
