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Introduction: SB3 is a trastuzumab biosimilar approved in Australia, Brazil, Canada, the European Union, the Republic of Korea, Switzerland, and the USA. This real-world study evaluated safety and effectiveness of SB3 as part of the Korean post approval safety management system. Methods: This post-marketing surveillance in Korea included patients in line with approved indications, i.e., patients with early or metastatic breast cancer or metastatic gastric cancer. Safety outcomes were adverse events (AEs) and adverse drug reactions. Effectiveness outcomes were tumor response and event-free survival. Results: 424 patients were evaluated: 366 patients (86%) with early breast cancer, 53 patients (13%) with metastatic breast cancer, and 5 patients (1%) with metastatic gastric cancer. Among patients with breast cancer, AEs (mostly mild) and adverse drug reactions were reported by 158 (37.7%) and 57 (13.6%) patients, respectively. Most patients with an AE (141, 89.2%) had no change in treatment schedule. Treatment was temporarily suspended in 14 (8.9%) patients with an AE and completely discontinued in 7 (4.4%). Among patients with early and metastatic breast cancer who were evaluated for efficacy, objective response rates were 82.7% and 38.3%, respectively. Pathological complete response was 64.6% in patients with early breast cancer. Discussion/Conclusion: Safety and efficacy of SB3 demonstrated in this real-world study were comparable with previous studies of reference trastuzumab. [ABSTRACT FROM AUTHOR]

We used a hydrogel-mediated dual drug delivery approach, based on an injectable glycol chitosan (GC) hydrogel, doxorubicin hydrochloride (DOX⋅HCl), and a complex of beta-cyclodextrin (β-CD) and paclitaxel (PTX) (GDCP) for breast cancer therapy in vitro and in vivo. The hydrogel was swollen over 3 days and remained so thereafter. After an initial burst period of 7 hours, the two drugs were released in a sustained manner for 7 days. The in vitro cell viability test showed that GDCP had a better anticancer effect than well plate and DOX⋅HCl/PTX (DP). In addition, the in vivo tests, which evaluated the anticancer effect, systemic toxicity, and histology, proved the feasibility of GDCP as a clinical therapy for breast cancer. [ABSTRACT FROM AUTHOR]

We aimed to examine the association between dietary isoflavone intake and the risk of breast cancer recurrence and summarize evidence on the role of dietary isoflavone intake in breast cancer prognosis. This prospective study included 592 breast cancer survivors who completed a dietary assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Of the studies published until May 31, 2023, that were searched in PUBMED and EMBASE databases, 14 studies were selected. Adjusted HRs were combined using fixed- or random-effects models. During the median follow-up of 4.3 years, 47 recurrences were identified. The HR (95% CI) for recurrence comparing the highest versus the lowest tertile of isoflavones intake was 1.29 (0.60–2.78). In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs (95% CIs) comparing the extreme categories were 0.81 (0.67–0.98) for recurrence and 0.85 (0.76–0.96) for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivors and warrants further investigation. [ABSTRACT FROM AUTHOR]

BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan–Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted. [ABSTRACT FROM AUTHOR]

This study investigated the prognostic value of FDG PET/CT radiomic features for predicting recurrence in patients with early breast invasive ductal carcinoma (IDC). The medical records of consecutive patients who were newly diagnosed with primary breast IDC after curative surgery were reviewed. Patients who received any neoadjuvant treatment before surgery were not included. FDG PET/CT radiomic features, such as a maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), skewness, kurtosis, entropy, and uniformity, were measured for the primary breast tumor using LIFEx software to evaluate recurrence-free survival (RFS). A total of 124 patients with early breast IDC were evaluated. Eleven patients had a recurrence (8.9%). Univariate survival analysis identified large tumor size (>2 cm, p = 0.045), high Ki-67 expression (≥30%, p = 0.017), high AJCC prognostic stage (≥II, p = 0.044), high SUVmax (≥5.0, p = 0.002), high MTV (≥3.25 mL, p = 0.044), high TLG (≥10.5, p = 0.004), and high entropy (≥3.15, p = 0.003) as significant predictors of poor RFS. After multivariate survival analysis, only high MTV (p = 0.045) was an independent prognostic predictor. Evaluation of the MTV of the primary tumor by FDG PET/CT in patients with early breast IDC provides useful prognostic information regarding recurrence. [ABSTRACT FROM AUTHOR]

Highlights: [•] Solution-processed amorphous IZO TFTs were fabricated at 250°C. [•] The hydroxyl radical was effectively oxidized IZO thin film. [•] The carbon-related compounds were dissociated by deep UV irradiation. [ABSTRACT FROM AUTHOR]

Objective: We investigated the contribution of supplement use to total nutrient intake, the prevalence of inadequate nutrient intake and the factors associated with supplement use among breast cancer survivors. Methods: A total of 701 Korean breast cancer survivors were included. We calculated the contribution of dietary supplements to total nutrient intake and the proportion of the population below the estimated average requirements (EARs) or exceeding the tolerable upper intake levels (ULs). Stepwise logistic regression was used to identify factors associated with dietary supplement use. Results: A total of 66.5% of the survivors used dietary supplements, with multivitamins and minerals being the most commonly consumed ones. The per cent contribution of supplement to the total intake was the highest for vitamin C. 28.2%–55.4% of the non‐users consumed below the EAR of riboflavin, folate and calcium; 6.1%, 4.9% and 6.5% of the supplement users consumed above the UL of vitamins A and C, and iron, respectively. Supplement users had higher education levels or longer survival time. Conclusion: 66.5% of Korean breast cancer survivors used dietary supplements. A higher education level or prolonged survival time was associated with higher use of dietary supplements. [ABSTRACT FROM AUTHOR]

Prostaglandin-endoperoxide synthase-2 (PTGS2) plays a pivotal role in inflammation and carcinogenesis in human breast cancer. Our aim of the study is to find the prognostic value of PTGS2 in breast cancer. We conducted a multiomic analysis to determine whether PTGS2 functions as a prognostic biomarker in human breast cancer. We explored PTGS2 mRNA expressions using different public bioinformatics portals. Oncomine, Serial Analysis of Gene Expression (SAGE), GEPIA, ULCAN, PrognoScan database, Kaplan-Meier Plotter, bc-GenExMiner, USC XENA, and Cytoscape/STRING DB were used to identify the prognostic roles of PTGS2 in breast cancer. Based on the clinicopathological analysis, decreased PTGS2 expressions correlated positively with older age, lymph node status, the human epidermal growth factor receptor 2 (HER2) status (P <.0001), estrogen receptor (ER+) expression (P <.0001) Luminal A (P <.0001), and Luminal B (P <.0001). Interestingly, progesterone receptor (PR) (P <.0001) negative showed a high expression of PTGS2. Prostaglandin-endoperoxide synthase-2 was downregulated in breast cancer tissues than in normal tissues. In the PrognoScan database and, Kaplan-Meier Scanner, downregulated expressions of PTGS2 associated with poor overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival. The methylation levels were significantly higher in the Luminal B subtype. Through oncomine coexpressed gene analysis, we found a positive correlation between PTGS2 and interleukin-6 (IL- 6) expression in breast cancer tissues. These results indicate that downregulated expressions of PTGS2 can be used as a promising prognostic biomarker and Luminal B hyper methylation may play an important role in the development of breast cancers. However, to clarify our results, extensive study is required. [ABSTRACT FROM AUTHOR]

Purpose: Recently, the utility of the Kinect sensor-based reachable workspace analysis system for measuring upper extremity outcomes of neuromuscular and musculoskeletal diseases has been demonstrated. Here, we investigated its usefulness for assessing upper extremity dysfunction in breast cancer patients.Methods: Twenty unilateral breast cancer patients were enrolled. Upper extremity active range of motion was captured by the Kinect sensor, and reachable workspace relative surface areas (RSAs) were obtained. The QuickDASH was completed to assess upper extremity disability. General and breast cancer-specific quality of life (QOL) were assessed by the EORTC QLQ-C30 and EORTC QLQ-BR23.Results: The total RSA ratio of the affected and unaffected sides ranges from 0.64 to 1.11. Total RSA was significantly reduced on the affected versus unaffected side (0.659 ± 0.105 vs. 0.762 ± 0.065; p = 0.001). Quadrant 1 and 3 RSAs were significantly reduced (0.135 ± 0.039 vs. 0.183 ± 0.040, p < 0.001; 0.172 ± 0.058 vs. 0.217 ± 0.031, p = 0.006). Total RSA of the affected side was strongly correlated with the numeric pain rating scale during movement (r = - 0.812, p < 0.001) and moderately with the QuickDASH (r = - 0.494, p = 0.027). Further, quadrant 3 RSA was correlated with EORTC QLQ-C30 role functioning (r = 0.576, p = 0.008) and EORTC QLQ-BR23 arm symptoms (r = - 0.588, p = 0.006) scales.Conclusions: The Kinect sensor-based reachable workspace analysis system was effectively applied to assess upper extremity dysfunction in breast cancer patients. This system could potentially serve as a quick and simple outcome measure that provides quantitative data for breast cancer patients. [ABSTRACT FROM AUTHOR]

Prostaglandin-endoperoxide synthase-2 (PTGS2) plays a pivotal role in inflammation and carcinogenesis in human breast cancer. Our aim of the study is to find the prognostic value of PTGS2 in breast cancer. We conducted a multiomic analysis to determine whether PTGS2 functions as a prognostic biomarker in human breast cancer. We explored PTGS2 mRNA expressions using different public bioinformatics portals. Oncomine, Serial Analysis of Gene Expression (SAGE), GEPIA, ULCAN, PrognoScan database, Kaplan-Meier Plotter, bc-GenExMiner, USC XENA, and Cytoscape/STRING DB were used to identify the prognostic roles of PTGS2 in breast cancer. Based on the clinicopathological analysis, decreased PTGS2 expressions correlated positively with older age, lymph node status, the human epidermal growth factor receptor 2 (HER2) status (P <.0001), estrogen receptor (ER+) expression (P <.0001) Luminal A (P <.0001), and Luminal B (P <.0001). Interestingly, progesterone receptor (PR) (P <.0001) negative showed a high expression of PTGS2. Prostaglandin-endoperoxide synthase-2 was downregulated in breast cancer tissues than in normal tissues. In the PrognoScan database and, Kaplan-Meier Scanner, downregulated expressions of PTGS2 associated with poor overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival. The methylation levels were significantly higher in the Luminal B subtype. Through oncomine coexpressed gene analysis, we found a positive correlation between PTGS2 and interleukin-6 (IL- 6) expression in breast cancer tissues. These results indicate that downregulated expressions of PTGS2 can be used as a promising prognostic biomarker and Luminal B hyper methylation may play an important role in the development of breast cancers. However, to clarify our results, extensive study is required. [ABSTRACT FROM AUTHOR]

Background: The BRAFV600E mutation in papillary thyroid carcinoma (PTC) is particularly prevalent in Korea, and a considerable number of wild-type BRAF PTCs harbor RAS mutations. In addition, subsets of other genetic alterations clearly exist, but their prevalence in the Korean population has not been well studied. Recent increased insight into noninvasive encapsulated follicular variant PTC has prompted endocrine pathologists to reclassify this entity as 'noninvasive follicular thyroid neoplasm with papillary-like nuclear features' (NIFTP). This study analyzed the genetic alterations among the histologic variants of PTC, including NIFTP. Methods: Mutations of the BRAF and RAS genes and rearrangement of the RET/PTC1, NTRK1, and ALK genes using 769 preoperative fine-needle aspiration specimens and resected PTCs were analyzed. Results: Molecular alterations were found in 687 (89.3%) of 769 PTCs. BRAFV600E mutation (80.8%) was the most frequent alteration, followed by RAS mutation and RET/PTC1, NTRK1, and ALK rearrangements (5.6%, 2.1%, 0.4%, and 0%, respectively). The low prevalence of NTRK1 fusions and the absence of an ALK fusion detected in Korea may also be attributed to the higher prevalence of the BRAFV600E mutation. There were significant differences in the frequency of the genetic alterations among the histologic variants of PTC. The prevalence of NIFTP in PTC was 2.7%, and among the NIFTPs, 28.6% and 57.1% harbored BRAF and RAS mutations, respectively. Clinicopathologic factors and mutational profiles between NIFTP and encapsulated follicular variant PTC with capsular invasion group were not significantly different. Conclusions: Genetic alterations in PTC vary among its different histologic variants and seem to be different in each ethnic group. [ABSTRACT FROM AUTHOR]

Whether preoperative F-18 fluorodeoxyglucose ( FDG)-positron emission tomography/computed tomography ( PET/ CT) can predict recurrence of papillary thyroid carcinoma ( PTC) remains unclear. Herein, we evaluated the potential of primary tumor FDG avidity for the prediction of tumor recurrence in PTC patients. A total of 412 PTC patients (72 males, 340 females; age: 47.2 ± 12.2 years; range: 17-84 years) who underwent FDG- PET/ CT prior to total thyroidectomy ( n = 350), subtotal thyroidectomy ( n = 2), or lobectomy ( n = 60) from 2007 to 2011 were analyzed. The predictive ability for recurrence was investigated among various clinicopathological factors, BRAFV600E mutation, and preoperative FDG avidity of the primary tumor using Kaplan-Meier (univariate) and Cox proportional hazards regression (multivariate) analyses. Of the 412 patients, 19 (4.6%) experienced recurrence, which was confirmed either by pathology ( n = 17) or high serum thyroglobulin level ( n = 2), during a mean follow-up period of 43.9 ± 16.6 months. Of the 412 patients, 237 (57.5%) had FDG-avid tumors (maximum standardized uptake value, 7.1 ± 7.0; range: 1.6-50.5). Kaplan-Meier analysis revealed that tumor size ( P = 0.0054), FDG avidity of the tumor ( P = 0.0049), extrathyroidal extension ( P = 0.0212), and lymph node ( LN) stage ( P < 0.0001) were significant predictors for recurrence. However, only LN stage remained a significant predictor in the multivariate analysis ( P < 0.0001). Patients with FDG-avid tumors had higher LN stage ( P < 0.0001), larger tumor size ( P < 0.0001), and more frequent extrathyroidal extension ( P < 0.0001). In conclusion, FDG avidity of the primary tumor in preoperative FDG- PET/ CT could not predict the recurrence of PTC. LN stage was the only identified predictor of PTC recurrence. [ABSTRACT FROM AUTHOR]

We evaluated the mammographic and histopathologic features of screening mammography-detected ductal carcinoma in situ (DCIS) based on the breast cancer subtypes determined by immunohistochemistry. A total of 94 patients with 94 screening mammography-detected DCIS were included in this study. Mammographically, human epidermal growth factor receptor 2 (HER2)-positive DCIS was more commonly associated with calcifications than estrogen receptor (ER)-positive and triple-negative DCIS ( P = .003). Histopathologically, HER2-positive DCIS and triple-negative DCIS were associated with high nuclear grade ( P ≤ .001) and comedo necrosis ( P ≤ .001) than ER-positive DCIS. [ABSTRACT FROM AUTHOR]

Background: Shear-wave elastography (SWE) has the potential to improve diagnostic performance of conventional ultrasound (US) in differentiating benign from malignant breast masses.Purpose: To investigate false positive or negative results of SWE in differentiating benign from malignant breast masses and to analyze clinical and imaging characteristics of the masses with false SWE findings.Material and Methods: From May to October 2013, 166 breast lesions of 164 consecutive women (mean age, 45.3 ± 10.1 years) who had been scheduled for biopsy were included. Conventional US and SWE were performed in all women before biopsy. Clinical, ultrasonographic morphologic features and SWE parameters (pattern classification and standard deviation [SD]) were recorded and compared with the histopathology results. Patient and lesion factors in the "true" and "false" groups were compared.Results: Of the 166 masses, 118 (71.1%) were benign and 48 (28.9%) were malignant. False SWE features were more frequently observed in benign masses. False positive rates of benign masses and false negative rates of malignancy were 53% and 8.2%, respectively, using SWE pattern analysis and were 22.4% and 10.3%, respectively, using SD values. A lesion boundary of the masses on US (P = 0.039) and younger patient age (P = 0.047) were significantly associated with false SWE findings.Conclusion: These clinical and ultrasonographic features need to be carefully evaluated in performance and interpretation of SWE examinations. [ABSTRACT FROM AUTHOR]

Objective RAS mutations are the most common mutations in thyroid nodules with indeterminate cytology by fine-needle aspiration cytology ( FNAC), and are mutually exclusive with BRAF mutations. However, the diagnostic utility of RAS mutation analysis is uncertain. We evaluated the diagnostic utility of RAS mutation analysis in indeterminate thyroid nodules. Design, patients, and measurements A total of 155 thyroid nodules (90 benign and 65 indeterminate) negative for BRAFV600E mutations on FNAC were analysed for mutations in RAS codon 61 using pyrosequencing methods. We evaluated diagnostic accuracy of RAS mutation for predicting thyroid malignancy based on the surgical pathologic diagnosis. Results Among the 65 BRAFV600E-negative indeterminate thyroid nodules identified by FNAC, 25 (38·5%) exhibited point mutations in RAS 61 consisting of 18 NRAS 61 (72%), and 7 HRAS 61 (28%) mutations. In contrast, only five of 90 (5·6%) nodules with benign cytology had RAS mutations. Only two of 25 (8·0%) RAS 61+ indeterminate nodules exhibited malignant ultrasonographic features. Of the 15 patients with RAS 61+-indeterminate nodules who underwent thyroid surgery, 14 (93·3%) were diagnosed as malignant, including 13 follicular variant of papillary thyroid carcinomas ( FVPTC), and one follicular thyroid carcinoma ( FTC). The average tumour size was 1·79 ± 0·62 cm. Multifocality was seen in 28·6% of cases, with 7·1% exhibiting extrathyroidal extension; no lymph node or distant metastases were evident. Based on the surgical pathologic diagnosis results, preoperative RAS 61 mutation analysis on FNAC exhibited 93·3% sensitivity, 75·0% specificity, 93·3% positive predictive value, 75·0% negative predictive value and 89·5% diagnostic accuracy for predicting malignancies. Conclusion Our results suggest that RAS mutation analysis holds great promise as a preoperative diagnostic tool for predicting FVPTC in cytologically and sonographically indeterminate nodules negative for BRAF mutations. [ABSTRACT FROM AUTHOR]

Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n=57), BRAF K601E (n=11), or RAS (n=64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC. [ABSTRACT FROM AUTHOR]

Chronic shoulder pain is a common complication in breast cancer patients after surgery. Chronic shoulder pain after breast cancer surgery was formerly considered as neuropathic pain, however the pathophysiology including structural damages has not been assessed comprehensively. We hypothesized that the structural change could be one of the cause of shoulder pain after breast cancer surgery and evaluated various ultrasonography findings of the shoulder in breast cancer patients with chronic shoulder pain. Patients who were suffering from chronic shoulder pain on unilateral side for at least 3 months after breast cancer surgery were enrolled from a single tertiary hospital. Demographic and clinical data were collected at the baseline. Articular and adjacent structures of both shoulders (painful and contralateral side) were evaluated by ultrasonography. The ultrasonography findings were compared between painful and contralateral sides. Logistic regression analysis was performed to determine the factors associated with abnormal ultrasonography findings. Fifty-two female patients (average age of 55) were enrolled. Significantly more abnormal ultrasonography findings were observed in the painful side than in the contralateral side [39 (75.0%) vs 11 (21.2%), P < 0.001]. The coracohumeral ligament was significantly thicker in the painful side than in the contralateral side (2.48 ± 0.69 vs 1.54 ± 1.25 mm, P < 0.001); adhesive capsulitis was also more frequent in the painful side [14 (26.9%) vs 0, P < 0.001]. Furthermore, patients with a history of breast cancer surgery on the ipsilateral side were associated with abnormal ultrasonography findings and adhesive capsulitis. This study is the first to evaluate ultrasonography in patients with chronic shoulder pain after breast cancer surgery. The results showed that ultrasonography could reveal several structural problems in these patients. [ABSTRACT FROM AUTHOR]

Background: To clarify the effect of anaesthetic agents on cancer immunity, we evaluated the effects of propofol and sevoflurane on natural killer (NK) cell, cytotoxic T lymphocyte (CTL) counts and apoptosis rate in breast cancer and immune cells co-cultures from patients who underwent breast cancer surgery.Methods: Venous blood samples were collected after inducing anaesthesia and at 1 and 24 h postoperatively in patients who had undergone breast cancer surgery. The patients were allocated randomly to the propofol- or sevoflurane-based anaesthesia groups. We counted and detected apoptosis in cancer cell, NK cell and CTL of patients with breast cancer by co-culture with a breast cancer cell line in both groups. We also evaluated changes in the cytokines tumour necrosis factor-alpha, interleukin (IL)-6 and IL-10 during the perioperative period.Results: Forty-four patients were included in the final analysis. No difference in NK cell count, CTL count or apoptosis rate was detected between the groups. Furthermore, the number of breast cancer cells undergoing apoptosis in the breast cancer cell co-cultures was not different between the groups. No changes in cytokines were detected between the groups.Conclusion: Although basic science studies have suggested the potential benefits of propofol over a volatile agent during cancer surgery, propofol was not superior to sevoflurane, on the aspects of NK and CTL cells counts with apoptosis rate including breast cancer cell, during anaesthesia for breast cancer surgery in a clinical environment.Trial Registration: NCT02758249 on February 26, 2016. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer.Methods/design: Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively.Discussion: This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.Trial Registration: ClinicalTrials.gov Identifier NCT01589367. [ABSTRACT FROM AUTHOR]