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Purpose To investigate the mechanism through which hyperthermia promotes exosome secretion and drug sensitivity in adriamycin-resistant breast cancer. Materials and Methods We first evaluated the effect of hyperthermia on adriamycin-resistant breast cancer viability and used transmission electron microscopy, nanoparticle tracking analysis, and a bicinchoninic acid kit to validate the effect of hyperthermia on exosome secretion. The effective targeting molecules and pathways changed by hyperthermia were explored by RNA microarray and verified in vitro. The adriamycin-resistant MCF-7/ADR cells co-incubated with the exosomes produced by MCF-7/ADR cells after hyperthermia were assessed. The uptake of exosomes by MCF-7/ADR cells after hyperthermia treatment was evaluated by confocal microscopy. Finally, the mechanism through which hyperthermia promotes exosome secretion by hyperthermia was determined. Results Hyperthermia significantly suppressed the growth of adriamycin-resistant breast cancer cells and increased drug sensitivity by upregulating FOS and CREB5, genes related to longer overall survival in breast cancer patients. Moreover, hyperthermia promoted exosome secretion through Rab7b, a small GTPase that controls endosome transport. The upregulated FOS and CREB5 antioncogenes can be transferred to MCF-7/ADR cells by hyperthermia-treated MCF-7/ADR cell-secreted exosomes. Conclusions Our results demonstrated a novel function of hyperthermia in promoting exosome secretion in adriamycin-resistant breast cancer cells and revealed the effects of hyperthermia on tumor cell biology. These hyperthermia-triggered exosomes can carry antitumor genes to the residual tumor and tumor microenvironment, which may be more beneficial to the effects of hyperthermia. These results represent an exploration of the relationship between therapeutic strategies and exosome biology.

Recurrence, metastasis, and drug resistance are still big challenges in breast cancer therapy. Internal and external stresses have been proven to substantially facilitate breast cancer progression through molecular and systemic mechanisms. For example, endoplasmic reticulum stress (ERS) results in activation of the unfolded protein response (UPR), which are considered an important cellular stress response. More and more reports indicate its key role in protein homeostasis and other diverse functions involved in the process of breast cancer progression. Therefore, therapies targeting the activation of ERS and its downstream signaling pathways are potentially helpful and novel tools to counteract and fight breast cancer. However, recent advances in our understanding of ERS are focused on characterizing and modulating ERS between healthy and disease states, and so little attention has been paid to studying the role and clinical application of targeting ERS in a certain cancer. In this review, we summarize the function and main mechanisms of ERS in different molecular types of breast cancer, and focus on the development of agents targeting ERS to provide new treatment strategies for breast cancer.

More initial clinical node-positive breast cancer patients achieve axillary pathological complete response (ax-pCR) after neoadjuvant systemic therapy (NST). Restaging axillary status and performing de-escalated surgical procedures to replace routine axillary lymph nodes dissection (ALND) is urgently needed. Targeted axillary lymph node biopsy (TLNB) is a novel de-escalated surgical strategy marking metastatic axillary nodes before NST and targeted dissection and biopsy intraoperatively to tailor individual axillary management.This study provided a systematic review and meta-analysis to evaluate the feasibility and diagnosis accuracy of TLNB. Prospective and retrospective clinical trials on TLNB were searched from Pubmed, Embase, and Cochrane. Identification rate (IFR), false-negative rate (FNR), negative predictive value (NPV), and rate of ax-pCR were the outcomes of this meta-analysis.One thousand nine hundred and twenty patients attempted TLNB, with an overall IFR of 93.5% (95% confidence interval [CI] 90.1%-96.2%). IFR of three nodal marking methods, namely iodine seeds, clips, and carbon dye, was 95.6% (95% CI 91.2%-98.7%), 91.7% (95% CI 87.3%-95.4%), and 97.1% (95% CI 89.1%-100.0%), respectively. Of them, 847 patients received ALND, with an overall FNR of 5.5% (95% CI 3.3%-8.0%), and NPV ranged from 90.1% to 96.1%. Regression analysis showed that the overlap of targeted and sentinel biopsied nodes might associate with IFRs and FNRs.TLNB is a novel, less invasive surgical approach to distinguish initial node-positive breast cancer that achieves negative axillary conversion after NST. It yields an excellent IFR with a low FNR and a high NPV. A combination of preoperative imaging, intraoperative TLNB with SLNB, and postoperative nodal radiotherapy might affect the future treatment paradigm of primary breast cancer with nodal metastases.

Human epidermal growth factor receptor 2 (HER2)-positive is a particularly aggressive type of the breast cancer. Trastuzumab-based therapy is a standard treatment for HER2-positive breast cancer, but some patients are resistance to the therapy. There are no known diagnostic biomarkers to improve the early diagnosis of HER2-positive breast cancer and the clinical utility of trastuzumab therapy. Using ultrahigh-performance liquid time of flight mass spectrometry (UPLC-TOF-MS)-based serum metabolomics and multivariate statistical analysis, we investigated and identified the circulating metabolites L-arginine and arachidonic acid were elevated in trastuzumab-responsive and trastuzumab-resistant HER2-positive breast cancer patients, and increased until reaching their peaks in trastuzumab-resistant HER2-positive breast cancer patients. Moreover, an equation for assessing the risk scores based on linear logistic regression models involving L-arginine and arachidonic acid was created, which was beneficial for revealing metabolic changes in HER2-positive breast cancer and enhancing current trastuzumab-based therapy. In summary, we develop serum-based metabolic biomarkers for diagnosis of HER2-positive breast cancers and predicts the therapeutic effects of trastuzumab therapy.

Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.

Transforming growth factor-β (TGF-β) signaling pathway is a key regulator of various cancer biologies, including cancer cell migration, invasion, angiogenesis, proliferation, as well as apoptosis, and it is one of indispensable signaling pathways during cancer metastasis. TGF-β signaling pathway can regulate and be regulated by a series of molecular and signaling pathways where microRNAs (miRNAs) seem to play important roles. miRNAs are small non-coding RNAs that can regulate expressions of their target genes. Emerging evidence suggest that miRNAs participate in various biological and pathologic processes such as cancer cells apoptosis, proliferation, invasion, migration, and metastasis by influencing multiple signaling pathways. In this article, we focus on the interaction between miRNAs and TGF-β in breast cancer (BC) metastasis through modulating invasion-metastasis-related factors, including epithelial-to-mesenchymal transition (EMT), cancer stem cells (CSCs), matrix metalloproteinase (MMP), tissue inhibitors of MMPs (TIMPs), cell adhesion molecules (CAMs), and tumor microenvironment (TME). Through a clear understanding of the complicated links between TGF-β pathway and miRNAs, it may provide a novel and safer therapeutic target to prevent BC metastasis.

Background This study was guided by principles of the theoretical system of evidence-based medicine. In particular, when searching for evidence of breast cancer, a measuring scale is an instrument for evaluating curative effects in accordance with the laws and characteristics of medicine and exploring the establishment of a system for medically assessing curative effects. At present, there exist few tools for evaluating curative effects. Patient- reported outcomes (PROs) refer to outcomes directly reported by patients (without input or explanations from doctors or other intermediaries) with respect to all aspects of their health. Data obtained from PROs provide evidence of treatment effects. Materials and methods In accordance with the tenets of theoretical medicine and ancient medical theory regarding breast cancer, principles for developing a PRO scale were established, and a theoretical model was developed and a literature review was performed, items from this pool were combined and split, and an initial scale was constructed. After a pilot survey and additional modifications, a pre-questionnaire scale was formed and used in a field investigation. After the application of statistical methods, the item pool was used to create a formal scale. The reliability, validity and feasibility of this formal scale were then assessed. Results In a clinical investigation, 479 responses were recovered, with an acceptance rate of 95%. a combination of various methods was employed, and the items that were selected by all methods or more than half of the methods were employed in the questionnaire. In these cases, the screening methods were combined with certain features of the item, A total of four domains and 38 items were reserved. The reliability analysis indicated that the PRO scale was relatively reliable. Conclusions Scientific assessment proved that the proposed scale exhibited good reliability and validity. This scale was readily accepted and could be used to assess the curative effects of medical therapy. However, given the limited scope of this investigation, the capacity for adapting this scale to incorporate other theories could not be determined.

Cancer susceptibility candidate 2 (CASC2), a long non-coding RNA (lncRNA), has been demonstrated to be a tumor suppressor in several types of cancer. However, the role and mechanism of CASC2 in breast cancer (BC) have not been investigated. In the present study, the expression and functions of CASC2 in BC were investigated. The expression of CASC2 was significantly decreased in BC tissues and cells compared with adjacent normal tissues and mammary epithelial cells, respectively. CASC2 overexpression inhibited the viability, migration and invasion, and elevated apoptosis of BC cells. In addition, CASC2 acted as a competing endogenous RNA for hsa-microRNA (miR)-96-5p and regulated the expression of its target gene, synoviolin (SYVN1). In miR-96-5p-overexpressed MDA-MB-231 cells, cell viability, migration and invasion was increased, and cell apoptosis was decreased, which was reversed by the upregulation of SYVN1. Taken together, the present study data indicated that decreased SYVN1 expression was a tumor suppressor, which inhibited the growth and metastasis of BC through the miR-96-5p/SYVN1 axis.

Background: Currently, exosomes that act as mediators of intercellular communication are being researched extensively. Our previous studies confirmed that these exosomes contain microRNAs (miRNAs) that could alter chemo-susceptibility, which is partly attributed to the successful intercellular transfer of multidrug resistance (MDR)-specific miRNAs. We also confirmed that β-elemene could influence MDR-related miRNA expression and regulate the expression of the target genes PTEN and Pgp, which may lead to the reversal of the chemoresistant breast cancer (BCA) cells. We are the first to report these findings, and we propose the following logical hypothesis: β-elemene can mediate MDR-related miRNA expression in cells, thereby affecting the exosome contents, reducing chemoresistance transmission via exosomes, and reversing the drug resistance of breast cancer cells. Methods: MTT-cytotoxic, miRNA microarray, real-time quantitative PCR, Dual Luciferase Activity Assay, and Western blot analysis were performed to investigate the impact of β-elemene on the expression of chemoresistance specific miRNA and PTEN as well as Pgp in chemoresistant BCA exosomes. Results: Drug resistance can be reversed by β-elemene related to exosomes. There were 104 differentially expressed miRNAs in the exosomes of two chemoresistant BCA cells: adriacin (Adr) - resistant MCF-7 cells (MCF-7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) that underwent treatment. Of these, 31 miRNAs were correlated with the constant changes in the MDR. The expression of miR-34a and miR-452 can lead to changes in the characteristics of two chemoresistant BCA exosomes: MCF-7/Adr exosomes (A/exo) and MCF-7/Doc exosomes (D/exo). The PTEN expression affected by β-elemene was significantly increased, and the Pgp expression affected by β-elemene was significantly decreased in both cells and exosomes. β-elemene induced a significant increase in the apoptosis rate in both MCF-7/Doc and MCF-7/Adr cells. Conclusions: Drug resistance can be reversed by β-elemene, which can alter the expression of some MDR-related miRNAs, including PTEN and Pgp in MCF-7/Adr and MCF-7/Doc in cells. It can therefore affect the exosome contents and induce the reduction of resistance transmission via exosomes.

Extracellular vesicles have emerged as important mediators of intercellular communication and play an active role in cancer, including breast cancer. Despite limited studies, initial observations suggest that these vesicles are important in breast physiology and pathophysiology. We here, in brief, describe their potential use as future biomarkers and therapeutic agents in breast cancer. Extracellular vesicles in blood and breast fluid may have a great potential to detect and predict the presence of breast cancer, and extracellular vesicles modulation may emerge as a therapeutic approach in cancer therapy.

Sodium hydrosulfide (NaHS) is an exogenous hydrogen sulfide (H2S)-releasing molecule and has antitumor potential against a wide variety of human cancer types. The effect of exogenous H2S on the invasion of breast cancer and the possible underlying mechanisms remain unknown. The present study aimed to investigate the in vitro effects of H2S on transforming growth factor-β1 (TGF-β1)-induced human breast cancer cells and the associated mechanisms. MCF-7 cells were incubated with TGF-β1 to induce epithelial-mesenchymal transition (EMT) and an MTT assay was performed to detect cell viability. Flow cytometry, using propidium iodide (PI) staining, was used to determine the stages of the cell cycle. Apoptosis was detected with Annexin V-fluorescein isothiocyanate and PI double staining. Western blotting was performed to detect the protein expression of cystathionine γ-lyase (CSE, an endogenous H2S producer), phospho-p38 (a signaling protein associated with apoptosis), and SNAI1 (Snail, associated with the induction of EMT). A Boyden chamber invasion assay was performed to detect tumor invasion. The results demonstrated that when NaHS was administered to TGF-β1-treated MCF-7 cells, the cells exhibited decreased proliferation, G0/G1 phase cell cycle arrest and increased apoptosis. NaHS treatment following TGF-β1 administration also resulted in decreased cell invasion and decreased EMT, which was indicated by decreased Snail protein expression. In addition, incubation with NaHS increased endogenous CSE protein expression and decreased p38 mitogen-activated protein kinase phosphorylation in MCF-7 cells stimulated by TGF-β1. Furthermore, the inhibition of endogenous CSE by DL-propargylglycine increased EMT in the MCF-7 cells treated with NaHS and TGF-β1. In conclusion, the present study provides insights into a novel anticancer effect of H2S on breast cancer cells through activation of the CSE/H2S pathway and decreased expression of phospho-p38.

Background: Multidrug resistance (MDR) directly contributes to the clinical failure of chemotherapy in breast cancer (BCA). β-elemene is a natural antitumor drug from plants. We previously confirmed that MDR could be reversed by β-elemene. In this study, we intended to investigate the reversal effect of β-elemene on MDR in human BCA adriacin (Adr) -resistant MCF-7 cells (MCF-7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) through the gene regulatory network. Methods: MTT-cytotoxic, miRNA microarray, Real-time quantitative PCR, Dual Luciferase Activity Assay, Western blot analysis were performed to investigate the impact of β-elemene on chemo-resistant BCA cell suvival, and its impact on the expression of chemo-resistance specific miRNA and the downstream target genes PTEN and Pgp. Results: Compared with the miRNAs expression profiles of MCF-7/Adr and MCF-7/Doc cell lines from our previous studies, there were 322 differentially expressed miRNAs in MCF-7/Adr and MCF-7/Doc breast cancer cells with β-elemene intervention (50μM/L) for 30h, and 6 miRNAs were significantly up-regulated and 12 miRNAs were significantly down-regulated in both MCF-7/Adr and MCF-7/Doc. We have testified that 5 miRNA is related to MDR before, in this study, the expression of miR-34a, miR-222, miR-452 and miR-29a can lead to changes of the characteristics of chemo-resistant MCF-7/Adr and MCF-7/Doc. The PTEN expression under intervention of β-elemene was significantly increased and Pgp expression under β-elemene intervention was significantly decreased in both cell lines. Conclusions: β-elemene could influence MDR related miRNA expression and subsequently regulate the expression of the target genes PTEN and Pgp, which may lead to reduction of the viability of the chemo-resistant breast cancer cells.

The high resistant rate of Adriamycin (Adr) is associated with a poor prognosis of breast cancer in women worldwide. Since miR-222 might contribute to chemoresistance in many cancer types, in this study, we aimed to investigate its efficacy in breast cancer through PTEN/Akt/p27

Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients’ beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients’ persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8 % for the standard treatment group and the standard treatment plus patient support program group, respectively (P = 0.95). The mean times to treatment discontinuation were 231.2 days in the standard treatment group and 227.8 days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (P = 0.96). There was also no statistically significant difference in the reason for treatment discontinuation (P = 0.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratio = 3.9; 95 % CI, 1.1–13.7; P = 0.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients’ persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.

Purpose of review Anthracyclines and taxanes are the two most active classes of cytotoxic agents that are commonly used for the treatment of breast cancer. However, resistance to these agents has become a major clinical obstacle. The aim of the present review is to define the roles of noncoding RNA (ncRNA) in breast cancer progression and the development of chemotherapy resistance. The ultimate goal is to exploit ncRNAs as new therapeutic tools to overcome resistance. Recent findings Two important types of ncRNA include microRNA (miRNA) and long noncoding RNA (lncRNA). Both miRNA and lncRNA have recently impacted the field of breast cancer research as important pieces in the mechanistic puzzle of the genes and pathways involved in breast cancer development and progression. Summary Herein, we review the roles of miRNA and lncRNA in breast cancer progression and the development of chemotherapy resistance. Future research should include identification of ncRNAs that could be potential therapeutic targets in chemotherapy-resistant tumors, as well as ncRNA biomarkers that facilitate more tumor-specific treatment options for chemotherapy-resistant breast cancer patients.

// Yue-Mei Xu 1, * , Hong-Jiang Wang 2, * , Fang Chen 3, * , Wan-Hua Guo 4, * , Yan-Yang Wang 4, * , Hang-Yu Li 5, * , Jin-Hai Tang 6, * , Ying Ding 1 , Ya-Chen Shen 7 , Min Li 1, 7 , Wen-Ying Xuan 1 , Lin-Hui Liu 1 , Jia Wang 2 , Xue-Rong Wang 1 , Ze-Jun Gao 1 , Xiu-Bin Liang 7 , Dong-Ming Su 1, 7, 8 1 State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China 2 Department of Breast Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China 3 Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China 4 Department of Nuclear Medicine, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, China 5 Department of General Surgery, 4th Affiliated Hospital, China Medical University, Shenyang, China 6 Department of General Surgery, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, China 7 Center of Metabolic Research, Nanjing Medical University, Nanjing, China 8 Center of Cellular therapy, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Dong-Ming Su, e-mail: sudongming@njmu.edu.cn Keywords: HRD1, breast cancer, metastasis, IGF-1R, degradation Received: May 02, 2015 Accepted: October 09, 2015 Published: October 19, 2015 ABSTRACT HRD1 (3-hydroxy-3-methylglutaryl reductase degradation) is an E3 ubiquitin ligase. We found that HRD1 was significantly downregulated in 170 breast cancer tissues. Low tumoral HRD1 expression was correlated with clinicopathological characteristics and a shorter survival in breast cancer patients. P65 specifically bound to the HRD1 promoter and inhibited HRD1 expression. Suppression of NF-κB activity reversed IL-6-induced downregulation of HRD1 expression. HRD1 interacted with IGF-1R and promoted its ubiquitination and degradation by the proteasome. Overexpression of HRD1 resulted in the inhibition of growth, migration and invasion of breast cancer cells in vitro and in vivo . Furthermore, HRD1 attenuated IL-6-induced epithelial-mesenchymal transition in MCF10A cells. These findings uncover a novel role for HRD1 in breast cancer.

A compariosn was made of survival outcomes of oncoplastic breast conserving therapy (oBCT) with nipple- areolar (NAC) preservation in women with centrally located breast cancer (CLBC) undergoing modified radical mastectomy (MRM) in China in a matched retrospective cohort study. We used a database including patients who received oBCT (n=91) or MRM (n=182) from 2003 to 2013 in our hospital. Matching was conducted according to five variables: age at diagnosis, axillary lymph node status, hormone receptor status, human epidermal growth factor-like receptor 2 status (HER-2) and tumor stage. The match ratio was 1:2. Median follow-up times for the oBCT and MRM groups were 83 and 81 months, respectively. There were no significant differences in 87-month overall, local, or distant recurrence-free survival between patients with oBCT and MRM (89%vs.90%; 93%vs.95%; 91%vs.92%;). For appropriate breast cancer patients, oBCT for CLBC is oncologically safe, oncoplastic techniques improving cosmetic outcomes.

To investigate the clinical efficacy of the immediate breast reconstruction following breast-conserving surgery for centrally located breast cancer.From January of 2006 through December of 2011, 30 women with centrally located breast cancer of stage I or II was treated by breast-conserving surgery removing or not removing the nipple-areola complex. All the patients received immediate breast reconstruction with adjacent gland tissue flap or latissimus dorsi myocutaneous flap. The breast shape and complication were observed. All the patients were followed up.The thirty women underwent the breast-conserving surgery successfully, in which 12 cases received immediate breast reconstruction with adjacent gland tissue flap and 18 cases received immediate breast reconstruction with latissimus dorsi myocutaneous flap. The superior rate of the aesthetic effect was 90% (27/30) according to JCRT in one week or six months after surgery. No recurrence and metastasis were observed after a median follow-up of 38 months ( range 4-72 months).The immediate breast reconstruction following breast-conserving surgery for centrally located breast cancer at early stage is satisfactory for the aesthetic result and clinical efficacy, and deserves further clinical application.

There has been an increase in the incidence of breast cancer in China, but no definite risk and protective factors for breast cancer have been identified in Chinese females. This study was designed to identify the risk factors for female breast cancer in North and East China.A 1:3 matched, case-control study was conducted. All of the subjects in the case and control groups were selected from a previous epidemiological survey of 122 058 females aged 25 to 70 years. Single and multiple Logistic regression analyses were used to study potential factors in the development of breast cancer.Significant differences at the level of α=0.20 between case and control groups were observed for the following factors: economic status, social status, family annual income, bean product consumption, body mass index (BMI), family history of breast cancer in the first or second degree, number of miscarriages, menstrual pattern, benign breast disease history, nipple leakage, inverted nipple, history of diabetes mellitus, history of hypertension, history of ovarian cyst, physical exercise, current and global quality of life satisfaction, healthy behavior and prevention, and scores of breast cancer-related knowledge. After Cox-regression model analysis (α=0.10), six factors were found to be significantly related to breast cancer, of which the ORs and 95%CIs were: BMI, 1.696 (1.169-2.460, P=0.005); benign breast disease history, 2.672 (0.848-8.416, P=0.093); family history of breast cancer, 7.080 (1.758-28.551, P=0.006); number of miscarriages, 1.738 (1.014-2.978, P=0.044); global quality of life satisfaction, 3.044 (1.804-5.136, P=0.000); healthy behavior and prevention, 3.294 (1.692-6.412, P=0.000).A comprehensive range of factors related to breast cancer was identified. Women should be educated about a healthy lifestyle, especially those with a family history of breast cancer or a personal history of benign breast disease.

To investigate the safety and long-term survival with weekly paclitaxel combined with cisplatin (wTP) as a postoperative adjuvant chemotherapy regimen for breast cancer.Patients with breast cancer were treated postoperatively with paclitaxel 40 mg/m2 intravenously on days 1, 8 and 15, cisplatin 25 mg/ m2 also intravenously on days 1,8 and 15, repeated every 21-28 days as a cycle. Toxicity and survival rate were evaluated after chemotherapy.Between September 1993 and August 2001, 20 patients were enrolled. Median age was 52 years (range, 35-71 years). According to the TNM stage system, all patients were staged II or III. Median number of chemotherapy cycles was 3 (range, 1-6), and 10 patients received 4 to 6 cycles of wTP. After a median follow-up of 83 months, 2 deaths and 6 relapses were documented. The five year overall survival rate was 90%. All patients could be evaluated with regard to toxicity. No treatment related deaths were recorded. Neutropenia occurred in 75% of patients during treatment, all recovering after G-CSF injection. Other symptoms included nausea/vomiting, elevation of transaminase, urea nitrogen/creatinine and alopecia.wTP is safe and effective at the doses tested. However, a randomized clinical trial is needed to compare wTP with other conventional adjuvant regimens of breast cancer postoperatively.

To compare the safety and efficacy of a combination of 5-Fu, pirarubicin and CTX (FPC) with FEC as a postoperative adjuvant chemotherapy for breast cancer.A total of 655 breast cancer patients were treated postoperatively in Jiangsu Cancer Hospital and Research Institute from 1995-2005, 292 were treated with FPC (5-Fu 500 mg/m2 i.v. gtt on day 1, pirarubicin 40 mg/m2 i.v. on day 1, CTX 500 mg/m2 i.v. on day 1 and a cycle repeated every 21-28 days for totally 4-6 cycles); 363 with FEC (5-Fu 500 mg/m2 i.v. gtt on day 1, epirubicin 50 mg/m2 i.v. on day 1 and day 2, CTX 500 mg/m2 i.v. on day 1 and a cycle repeated every 21-28 days for totally 4-6 cycles). Toxicity was evaluated after each cycle of chemotherapy.Main side effects in both FPC and FEC groups were leukopenia and gastrointestinal toxicity, with a 5 year survival rate 88.7% in FPC and 85.7% in FEC group.FPC regimen is safe with superior long-term survival rate when compared with FEC, thus could be recommended as a postoperative chemotherapy regimen for Chinese patients with breast cancer.

The aim of this study is to investigate clinical significance of miR-155 expression in breast cancer.TaqMan real-time RT-PCR was performed to detect miR-155 expression in breast cancer tissues. The correlation of miR-155 expression with clinicopathological factors and prognosis of breast cancer patients was analyzed. Then, the prognostic value of miR-155 expression was analyzed by univariate and multivariate analyses. Moreover, the effect of miR-155 expression on phenotypes of breast cancer cell was determined by antisense technology.The relative expression of miR-155 was significantly higher in breast cancer tissues than in corresponding nontumor tissues. High miR-155 expression was correlated with higher tumor grade, advanced tumor stage and lymph node metastasis (P = 0.012, 0.001, and 0.003, respectively). Kaplan-Meier survival analysis indicated that the disease-free and overall survival rates of high miR-155 group were significantly lower than those of low miR-155 group (P = 0.038 and 0.029, respectively). Multivariate analysis showed that high miR-155 expression was a poor prognostic factor (P = 0.009). Furthermore, antisense targeting miR-155 could inhibit growth, induce cell arrest in G(0) /G(1) phase, enhance apoptosis, and increase radiosensitivity in breast cancer cells.MiR-155 expression might be an independent prognostic factor and a therapeutic target for human breast cancer.

To evaluate the relationship between physiological, reproductive factors and risk of breast cancer, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. All subjects completed an in-person interview. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as measures of risk for breast cancer. The results have revealed that there was an increasing risk of breast cancer, include early age at menarche(≤ 13 year), late age at menopause(50 year) and older age at first pregnancy (≤ 30 year). Breastfeeding was associated significantly with a reduced risk of breast cancer. Women who had history of breastfeeding were at significantly decreased OR (0.44, 95%CI: 0.27-0.73). The protective effects of breastfeeding for breast cancer seemed greater for women who had extended duration of breastfeeding during their lifetime (p for linear trend: 0.0095). These results suggested that physiological and reproductive factors may play important roles in the development of breast cancer among Jiangsu' women of China.

To evaluate the efficacy and toxicity of cisplatin and vinorelbine (NP) for postoperative adjuvant chemotherapy of completely resected breast cancers.Between September 1994 and April 2005, 91 Chinese breast cancer patients, with pathologically-confirmed adenocarcinoma in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received postoperative vinorelbine at 25 mg/m² on days 1 and 8, and cisplatin 25mg/m2 on days 1 to 3, this regimen being repeated every 3 weeks.Median age was 49 years (range, 25-69 years). According to the TNM stage system, stage I, II, IIIA patients accounted for 7.7%, 58.2% and 34.1%, respectively. The median number of chemotherapy cycles was 4.5 (range, 1-8), over half of the patients receiving 4 to 6 NP cycles. After a median follow-up of 48 months, 11 deaths and 29 relapses were documented. Median disease-free survival was 45 months, with disease-free and overall survival at 5 years being 76% and 88.7%, respectively. All patients could be evaluated with regard to toxicity, 17 (18.7%) developing grade III neutropenia during treatment, but all recovering after recombinant human granulocyte colony stimulating factor (G-CSF) injection, 3 suffering thrombocytopenia (3.3%), 5 anemia (5.5%) and 5 nausea/vomiting (5.5%). No treatment related deaths occurred.NP is an effective and feasible treatment for completely resected breast cancer cases at the doses tested. A randomized clinical trial is now needed to compare NP with other conventional regimens.

To compare the safety and efficacy of a combination of vinorelbine and epirubicin (NE) with fluorouracil/epirubicin/cyclophosphamide (FEC) as a postoperative adjuvant chemotherapy for breast cancer.Breast cancer patients were treated postoperatively in Jiangsu Cancer Hospital and Research Institute from 1997 to 2006 with either the NE regimen (vinorelbine 40 mg/m2 iv on day 1 and day 8, epirubicin 50 mg/m2 iv on day 1 and day 2, and a cycle repeated every 21-28 days for totally 4-6 cycles) or the FEC regimen (5-Fu 500 mg/m2 iv gtt on day 1, epirubicin 50 mg/m2 iv on day 1 and day 2, CTX 500 mg/m2 iv on day 1 and a cycle repeated every 21-28 days for totally 4-6 cycles). Toxicity was evaluated after each cycle of chemotherapy.Main side effects in both NE and FEC groups were neutropenia and gastrointestinal syndrome, with a 5 year survival rate of 87.9% in the NE and 85.2% in the FEC group.NE regimen is safe with good long-term survival rate, and thus could be recommended as a postoperative chemotherapy regimen for breast cancer.

To validate the clinical value of a computer assisted program (CAP), (visit website; http://xinenhuang.blog.sohu.com for details) for breast cancer patients who receive postoperative adjuvant chemotherapy.Patients with histologically confirmed breast cancer after mastectomy who received postoperative chemotherapy in Jiangsu Cancer Hospital and Research Institute were recruited in this study. All eligible patients are divided into three groups: group A, regimen of practical chemotherapy consistent with CAP prediction; group B, partly consistent with CAP prediction; group C, inconsistent with CAP prediction. Overall survival (OS) was compared among groups A, B and C to determine the efficacy of CAP.From November 1992 to July 2007, 310 female breast cancer patients were recruited into this study, with 112, 106 and 89, respectively, in groups A, B, and C. Prognosis of group A was better than both group B and C, with significantly different survival curves between group A and B (p=0.0004) and group A and C (p=0.0046).Validation showed our CAP to provide clinically valuable information on adjuvant chemotherapy for postoperative breast cancer patients.

To observe the safety of fixed dose rate gemcitabine by intravenous infusion (iv-FDR) for cancers.From January 1, 2007 to December 31, 2009, four patients who were pathologically diagnosed with advanced pancreatic or breast cancer were recruited into this study. They were treated by gemcitabine 10mg/m2/min iv-FDR on days 1 and 8, and combined with other chemotherapeutics, repeated every four weeks. Toxicity was determined in line with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC).The main toxicity was reversible myelosuppression; other side effects included gastrointestinal toxicity and liver impairment. Cardiac or renal toxicity was not detected.The toxicity of iv-FDR gemcitabine combination chemotherapy was well tolerated, so that iv-FDR gemcitabine deserves to be further studied as a treatment option.

To evaluate the relationship between body size, physical activity and risk of breast cancer, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. All subjects completed an in-person interview. The body mass index (BMI) was calculated based on weights and heights. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as measures of risk for breast cancer. Current height, weight and weight at around age 20 years were significantly positively correlated with risk of breast cancer. Obese women (current BMIor = 25 kg/m2) were at significantly increased risk for developing breast cancer (adjusted OR= 1.35, 95%CI: 1.01-1.81), but, between BMI at around age 20 years and risk of breast cancer showed an inverse association (P for trend = 0.001). Women who had middle physical force work were at significantly lowered OR (0.62, 95%CI: 0.41-0.93) compared with women of headwork. Using women who standing or ambulation per day less than one hour as the reference, women who standing or ambulation more than one hour had a decreased risk of breast cancer. Using women who slept less than 5 hours per day as the reference, the women who slept 5-8 hours were at significantly decreased risk of breast cancer. Women who had habit of recreational physical activity were at significantly decreased risk (adjusted OR= 0.68, 95%CI: 0.53-0.88), with an inverse association between the exercise times per week and risk of breast cancer (P for trend = 0.025). These findings support that breast cancer risk is associated with body size, and that moderate occupational and recreational physical activity has protective effects on breast cancer.

To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5, 10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk.A case-control study was conducted with 669 cases and 682 population-based controls in Jiangsu province of China. MTHFR C677T and A1298C genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Dietary folate intake was assessed by using an 83-item food frequency questionnaire. Odds ratios (OR) were estimated with an unconditional logistic model.The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37% (202/624), 48.88% (305/624) and 18.75% (117/624) in cases and 37.66% (235/624), 48.24% (301/624) and 14. 10% (88/624) in controls, respectively. The difference in distribution was significant (chi2 = 6.616, P = 0.037), the T/T genotype being associated with an elevated OR for breast cancer (1.62, 95% CI: 1.14 -2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47% (446/624), 27.08% (169/624) and 1.44% (9/624) in cases and 68.11%(425/624), 30.13% (188/624) and 1.76% (11/624)in controls,with no significant differences found (chi2 = 1.716, P= 0.424). Folate intake of cases [(263.00 +/- 137.38) microg/d] was significantly lower than that of controls [(285.12 +/- 149.61) microg/d] (t = -2. 830, P =0.005). Compared with the lowest tertile (or = 199.08 microg/d) of folate intake, the adjusted OR for breast cancer in the top tertile (or = 315.11 microg/d) was 0.70 (95% CI: 0.53 -0.92). Among individuals with the MTHFR A1298C A/A genotype,adjusted OR for breast cancer were 0.89 (95% CI: 0.62 - 1.27) and 1.69 (95% CI: 1.20 - 2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (X2trend = 11.372, P = 0.001).The findings of the present study suggest that MTHFR genetic polymorphisms,and dietary intake of folate may modify susceptibility to breast cancer.

To investigate the methods of lesion localization and surgical treatment for non-palpable breast cancer, presented with only small calcification lesion on the images.From November 2003 to August 2007, 61 patients with non-palpable lesion were finally pathologically diagnosed as early breast cancer (T1-2N0M0), based on the small calcification lesions shown by full field digital mammography (FFDM) through molybdenum target, and the rich blood supply shown by type-B ultrasonic examination. Accurate lesion-localization prior to surgical resection was conducted, and sample re-examination by FFDM was done after resection. Patients with single lesion underwent breast-conserving surgery, precise excision with the aid of image-guided wire localization, and stage I breast reconstruction was performed simultaneously using wide-based gland-tissue flap. Patients with multiple lesions received modified radical mastectomy.Among the 50 patients treated with breast-conserving surgery, the accuracy of localization for lesions was 100% (50/50), and all lesions were excised completely with a negative margin proven by FFDM re-examination and pathological examination. The superior rate of mammaplasty was 86.0% (43/50) according to JCRT criteria, with a compliance difference of 1.5 cm. Modified radical mastectomy was performed in 11 patients. The follow-up period in this series was from 6 to 58 months with a mean follow-up time of 39 months. Distant metastases were detected in only one patient and local recurrence was not observed yet.Lesion localization by FFDM in patients with non-palpable breast cancer is accurate and practical. In patients with single lesion, breast-conserving resection followed by synchronous stage I breast reconstruction with wide-based gland-tissue flap is appropriate.

To establish a method for SNP genotyping of multi-genes by allele-specific oligonucleotide probe ligation mediated by a thermostable ligase, and to explore the genetic polymorphisms of drug-metabolizing enzymes in breast cancer patients and their association with chemotherapeutic responses.10 SNP loci of enzyme genes related to chemotherapeutic drugs such as taxanes, anthracyclines and cyclophosphamide were selected, and were genotyped for blood samples from 126 breast cancer patients by the established method. Their correlations with therapeutic responses were retrospectively evaluated.The lower detection limit of genomic DNA by this developed method was 6.25 ng. The fluorescent peak locations of ligation products on ABI PRISM 377 DNA sequencer were accurate and consistent with prospective sizes in bases (Bias range 0.08 - 0.69 bp, x(-) = 0.31 bp, s = 0.18 bp). Same genotyping results were obtained for repeat tests of 8 random samples, which were further confirmed by sequencing analysis. The 10 SNP loci were polymorphic of different frequency in the breast cancer patients. The combinations with GSTP1 genotypes and GSTM1 genotypes were related to anthracycline-based chemotherapy efficacy (P = 0.037), and the low GSTs activity group (GSTP1 variant allele + GSTM1 null) showed the best effects (85.7%). GSTM1 genotypes and their combinations with GSTP1 and/or CYP3A5*3 genotypes were related to taxane-based therapy efficacy (P0.05 for all), and both the low GSTs activity group and the drug slow-metabolising group (low GSTs activity group + CYP3A5*3 wild allele) showed better effects (100%).The established method is reliable and applicable in multiplex SNPs genotyping of multi-genes. SNPs combination may have a better clinical application value for prediction of chemotherapeutic responses.

To study the changes in circulating VEGF and endostatin (ES) levels during chemotherapy for patients with breast cancer, and their correlation with efficacy of chemotherapy.40 breast cancer patients with metastases were included in this study. They received TAC/TEC, CAF/CEF, NP, CAP, CMF, TFP, TA or TC regime chemotherapy, respectively. Totally 120 serum samples were collected from the patients at three time points: before chemotherapy, the end of 1 and 5-6 chemotherapy cycles, and analyzed for VEGF and ES levels using ELISA. Tumor agiogenesis activity was evaluated by serum soluble vascular cell adhesion molecule (VCAM - 1) measured by ELISA as a surrogate marker.(1) Before chemotherapy, the median level of VEGF in patients with breast cancer was 496.6 pg/ml, 4.7 times higher than that of healthy controls (P0.001). The median level of ES was 95.5 ng/ml, 18.3% lower than that of healthy controls (P = 0.183). VCAM-1 was 1077.1 ng/ml and higher than that of controls (P0.001). The serum VEGF levels correlated with VCAM-1 levels, tumor staging and metastatic sites (P0.05). (2) At the end of 1 cycle of chemotherapy, the serum VEGF level (median 524.8 pg/ml) was higher than the pretreatment values (P = 0.047), whereas the levels of ES and VCAM-1 were not significantly altered (110.5 ng/ml, P = 0.055; and 975.6 ng/ml, P = 0.27). (3) At the end of 5-6 cycles, the changes in VEGF correlated with the response to chemotherapy. Serum VEGF levels in 27 patients with chemotherapy-responsive and stable disease showed a significant decrease (median 287.4 pg/ml) , but not observed in 13 patients with progressive disease. VCAM-1 also showed a treatment-related change like VEGF. However, chemotherapy might only have a minor effect on ES, because there was no significant difference in the ES levels among 5-6 cycle patients, 1 cycle patients and healthy controls, and neither between therapy-responsive patients.Intensive chemotherapy for breast cancer results in a significant decrease of serum VEGF level, which might be an indicator of the controlled disease status, and following the treatment-induced response or stabilization, the tumor angiogenesis seems to change into an anti-angiogenesis direction.

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

OBJECTIVES: This updated meta-analysis was conducted to assess the association between coffee consumption and breast cancer risk. METHODS: We conducted a systematic search updated July 2012 to identify observational studies providing quantitative estimates for breast cancer risk in relation to coffee consumption. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose-response relationships. RESULTS: A total of 26 studies (16 cohort and 10 case-control studies) on coffee intake with 49497 breast cancer cases were included in the meta-analysis. The pooled RR showed a borderline significant influence of highest coffee consumption (RR = 0.96; 95% CI 0.93-1.00), low-to moderate coffee consumption (RR = 0.99; 95% CI 0.95-1.04), or an increment of 2 cups/day of coffee consumption (RR = 0.98; 95% CI 0.97-1.00) on the risk of breast cancer. In stratified analysis, a significant inverse association was observed in ER-negative subgroup. However, no significant association was noted in the others. CONCLUSIONS: Our findings suggest that increased coffee intake is not associated with a significantly reduced risk of breast cancer, but we observe an inverse association in ER-negative subgroup analysis. More large studies are needed to determine subgroups to obtain more valuable data on coffee drinking and breast cancer risk.