bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic trans-arterial chemoembolization (TACE) in metastatic breast cancer.
Authors: Damian Silvia , Tessari Anna , Capri Giuseppe , Mariani Paola , Bianchi Giulia Valeria , Mariani Gabriella , Ricchini Francesca , Sica Lorenzo , De Benedictis Elena , Cresta Sara , Lanocita Rodolfo , Spreafico Carlo 
Published: March 2020

e12017 Background: Liver metastasis is one of the most frequent cause of death in breast cancer patients. Among loco-regional approaches available for solid tumor liver metastasis, TACE allows a prolonged intra-lesion exposure to chemotherapeutic agents. Initial studies have highlighted a benefit in terms of response rate (RR) and overall survival (OS) in breast cancer patients treated with TACE versus systemic chemotherapy. Methods: We have retrospectively evaluated 14 patients affected by breast cancer with liver metastasis. Patients had been selected for liver TACE according to the presence of liver metastasis as only site of disease, or in the event of further sites of metastasis that were stable or in response from the previous treatment. All the patients received one or more TACE with DC-Bead (Biocompatibles UK) 100-300 micron, loaded with a chemotherapeutic agent (doxorubicin, paclitaxel).The systemic therapy received by patients before TACE could be confirmed or changed according to disease response. Objective of the study was to evaluate the response rate to TACE and its correlation with the response to the very last treatment performed before it. As surrogate of efficacy, time to progression (TTP) and OS were analyzed. Results: Among the 14 treated patients (5 heavily pretreated, with more than three lines of chemotherapy) only one obtained a complete remission (RC). Four patients presented a partial remission (PR). Three of them were progressing from previous treatment and one had a PR. Stable disease (SD) after TACE was obtained in four cases: two of them had a progressive disease (PD) before TACE and two had a responsive disease. Five patients did not respond to TACE (one with PR from the previous line of therapy). Median TTP observed in responsive patients (CR + PR) was 4.5 times higher than non-responders (PD) (13.2 vs. 2.9 months). Patients with SD had a median TTP of 4.3 months. Median OS of responsive patients was 25.6 months vs. 17.5 and 19.2 months of patients with SD or PD respectively. Conclusions: In our experience, chemoembolization can represent a valid therapeutic option in breast cancer patients with liver metastasis, independently from the response to the previous systemic therapy, and may prolong survival.
Thirteen miRNAs involved in the response of breast cancer cells to doxorubicin.
Authors: Tormo Eduardo , Pineda BegoÃƒÂ±a , Ballester Sandra , Burgues Octavio , Serna Eva , Lluch Ana , Eroles Pilar 
Published: March 2020

e12019 Background: Mature microRNAs (miRNAs) are a class of naturally occurring, small non-coding RNA molecules, about 21–25 nucleotides. Growing evidence shows that miRNAs exhibit a variety of regulatory functions related to cell growth, development, and differentiation, and are associated with a wide variety of human diseases. Several miRNAs have been linked to cancer; since expression analysis studies have revealed perturbed miRNA expression in tumors compared to normal tissues. As a consequence, human miRNAs are likely to be highly useful as biomarkers, especially for future cancer diagnostics, and are emerging as targets for disease intervention. Since doxorubicin (DOX) has been used for a long time in breast cancer treatment, and resistance mechanisms are not clear understood, the aim of this work was to find a miRNA expression profile that could explain the regulation in different breast cancer cell lines under DOX treatment. Methods: Three breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7) were cultured in normal conditions and also treated with DOX. Total RNA containing small non-coding RNA was isolated and its expression profile was performed by using GeneChip miRNA 2.0 array. Real time PCR validation was carried out to confirm the results. Results: Principal Component Analysis (PCA) of the small non-coding RNA profiles showed different expression patterns between normal conditions and DOX treatment in each cell line separately. Taken together in a Heat Map, miRNA expression profiles of MDA-MB-231 and MDA-MB-468 cell lines were closer in both normal and DOX treatment conditions, while miRNA expression profile of MCF-7 cell line showed strong differences. Total of 13 common miRNAs between the three cell lines were found to be significantly affected by DOX treatment. PCR validation confirmed the results obtained. Conclusions: We conclude that 13 common miRNAs are responsables of changes compared to treatment with DOX in breast cancer cell lines MDA-MB-231, MDA-MB-468 and MCF-7. This miRNAs are mainly related with cellular processes such as cell differentiation, vascularisation, apoptosis and cell proliferation and also involved in other cellular processes, such as cell migration.
Is young age a poor prognostic factor in triple-negative breast cancer patients? Analysis of 363 patients from single institution registry.
Authors: Fayaz Mohamed Salah , Demian Gerges Attia , El-Sherify Mustafa , Abuzalouf Sadeq , George Thomas , Samir Suzanne , Eisa Heba El-Sayed , Nazmy Nashwa 
Published: March 2020

e12023 Background: Young age is a known independent poor prognostic factor for breast cancer. Few data exist about validating such prognostic factor in triple negative subtype of breast cancer. In this study, we evaluate the prognostic value of young age presentation in triple negative breast cancer (TNBC) patients who were diagnosed in Kuwait Cancer Control Center. Methods: This is a retrospective analysis of 363 patients diagnosed with TNBC between July 1999 and June 2009. Of these, 27% were diagnosed at or below the age of 40. Chi-square test was used to correlate the age with other prognostic factors. Survival measurements were estimated using Kaplan-Meier analysis. Statistical significance was calculated using the log-rank test. Results: There was no correlation between young age at presentation and other prognostic factors including grade, T stage, lymph node status, lymphovascular invasion, and Ki67 positivity. Similarly, young age was not statistically associated with poorer 5-years overall survival (78% for patients < 40 years compared to 72% for those > 40 years; p = 0.13), disease free survival (66% vs. 61%; p = 0.5) or locoregional recurrence free survival (81% vs. 83%; p = 0.7). Conclusions: Young age does not seem to negatively impact the survival of TNBC patients nor associated with poor prognostic factors in our study population. Further studies are needed to define new prognostic factors, e.g. molecular markers, in this subtype of patients rather than the conventional clinicopathologic prognostic factors.
Epirubicin/cyclophosphamide followed by docetaxel as the primary systemic therapy for locally advanced breast cancer: The final analysis of a phase II study.
Authors: Hirano Akira , Kamimura Mari , Ogura Kaoru , Hattori Akinori , Okubo Fumie , Inoue Hiroaki , Kinoshita Jun , Fujibayashi Mariko , Shimizu Tadao 
Published: March 2020

e12026 Background: The aim of this study was to evaluate the efficacy and safety of epirubicin/cyclophosphamide (EC) followed by docetaxel as the primary systemic therapy for locally advanced breast cancer. We previously reported pathological and objective response of patients receiving this treatment (Anticancer Res 28:4137-42, 2008). Another follow-up period of 5 years (5y) has since passed, and 5y overall survival (OS) and relapse-free survival (RFS) rates were determined. Methods: The primary endpoints were pathological and objective response in the breast and axilla, and toxicities. The secondary endpoints were the rate of breast-conserving surgery and the 5y OS and RFS rates. Patients with histologically diagnosed invasive breast cancer of T2-4 (>3 cm) or N1-3 were included in this study. The expected rate of pCR was 25%, and the sample size was calculated using the Simon method, with a type I error of 5% and a study power of 80%. The target enrollment was estimated to be 40 evaluable patients. pCR was defined as no evidence of residual invasive cancer, either in the breast or axilla. Patients received E (90 mg/m2) and C (600 mg/m2) every 3 weeks for 4 cycles followed by docetaxel (70 mg/m2) every 3 weeks for 4 cycles. Trastuzumab was not added to the regimen. Results: Forty-six patients were enrolled in this study. pCR were observed in 6 patients and the pCR rate was 13.0% (95% confidence interval, 3.4-22.7%). In particular, patients with HER2 positive tumor had a significantly higher rate of pCR than others (40.0% vs. 5.6%; p=0.0096). Overall, 5y OS was 93.2% and 5y RFS was 72.9%. According to ER, PgR, HER2 status, the following 4 subtypes were classified: luminal (ER and/or PgR+, HER2-; n=28), luminal-HER2 (ER and/or PgR+, HER2+; n=3), HER2 (ER and PgR-, HER2+; n=7) and triple negative (ER, PgR and HER2-; n=8). 5y OS and RFS were 96.4% and 70.6% in luminal type, 100% and 50% in luminal-HER2, 71.4% and 57.1% in HER2, 100% and 100% in triple negative, respectively. Conclusions: EC followed by docetaxel was an effective and well-tolerated treatment, and it is suggested that this treatment provides survival benefit especially for patients with triple-negative breast cancer.
Effects of acute doxorubicin exposure on caspase-mediated apoptosis in cardiomyocytes.
Authors: Demirci Umut , Yaman Melek , Bagriacik Umit E. 
Published: March 2020

e12036 Background: Doxorubicin binds to DNA-associated enzymes, intercalates the base pairs of the DNA and induces apoptosis in cancerous and healthy tissues especially in cardiomyocytes. Caspase mediated apoptosis in cardiomyocytes remains largely unknown. We investigated the role of doxorubicin via caspase system on apoptosis of cardiomyocytes. Methods: H9C2ratcardiomyocytes were incubated with doxorubicin a concentration of 10-6 Mfor 4 or 24 hours to perform gene expression and activity of caspases, respectively. Total RNA isolated and expression analysis were performed by real time PCR assay. Caspase activity was determined by colorimetric caspase assay kit. At least two fold increases in gene expression were accepted statistically significant. Results: In comparison to controls, bothof caspase expression and activity increased in doxorubicin-treated samples. Increase in expression of Caspase 9 and 2 as initiator caspases and caspases 7 and 3 as effector caspases were detected statistically higher than control values. In contrast, expression of caspase 1, 4, 6, 8 and 12 were detected lower than controls. Activity of both caspase 3 and 9 increased significantly. Conclusions: Acute doxorubicin administration caused a significant caspase activation on apoptosis of cardiomyocytes.
Triple negative breast cancer in African American women: Disparity between women in New Orleans versus Louisiana.
Authors: Loch Michelle Marie , Estrada John , Reske Thomas , Li Xiangrong , Chen Vivien , Wu Xiao-cheng 
Published: March 2020

e12501 Background: For years clinicians have made the empirical observation that there is an unusually high number of African American women (AAW) with triple-negative (Tneg) breast cancer (BC) in New Orleans (NO). Knowing the rate of Tneg BC in AAW is higher than white women (WW), we explored the hypothesis that AAW in NO have a higher rate of Tneg BC when compared to AAW in the rest of Louisiana (LA). Methods: We analyzed data from the Louisiana Tumor Registry, one of the NCI funded SEER registries, for the tumor characteristics of invasive female BC diagnosed in 2010, focusing on racial disparities; HER2 status was not available for prior to 2010 diagnosis. We explored the association of HER2 status with age, race, ER, PR, HER2, T, N, M to determine crude and adjusted odds ratios and rate distribution of subtypes using SEER*Stat and SAS programs. Results: Overall age-adjusted incidence rate of Tneg BC in AAW was 30 per 100,000 in NO, which was 24% higher than that in AAW in the rest of LA and two-fold the rate in WW of both NO and LA. The highest rate of Tneg BC was seen in AAW aged 65-69 in NO (184.97 per 100,000) compared with 81.5 per 100,000 in AAW aged 55-59 in LA. AAW with Tneg BC in NO were more likely to have more aggressive BC. Young age, black race, large tumor size, higher grade and TNM stage were significantly associated with the high risk of Tneg BC. After adjusting for age, geographic area, and other tumor characteristics, the higher risk of Tneg BC in AAW remained in NO compared with the rest of LA (OR=1.4; 95% CI: 1.01-1.87). Conclusions: AAW in NO are more likely to have poorly differentiated and Tneg BC compared to AAW in the rest of LA. This disparity remains when comparing our data to previously published literature in other parts of the US. We plan to continue our data analysis and compare NO data to the national average as the HER2 data become available in the SEER Program to better characterize the disparity. This newly identified disparity in the AAW population in NO has clinical implications and translational research potential as it enables us to broaden the understanding and treatment of this aggressive disease.
Breast cancer and diabetes.
Authors: Autier Philippe , Koechlin Alice , Robertson Chris , Bota Maria , Boniol Mathieu , Leroith Derek , Bolli Geremia , Rosenstock Julio , Boyle Peter 
Published: March 2020

e12507 Background: Diabetes and Breast Cancer are common conditions in women and there have been various links proposed between the two conditions. Methods: To clarify the potential association between diabetes, related factors, treatments and breast cancer risk, a series of meta-analyses were carried out following PRISMA guidelines. Results: For breast cancer at all ages, the risks obtained from prospective studies were: diabetes (SRR=1.27, 95% CI (1.16, 1.39); physical activity (SRR=0.88 (0.85, 0.92)); glycaemic load (SRR=1.05, (1.00, 1.10)); glycaemic index (SRR=1.05, (1.00, 1.09)); fasting glucose (SRR=1.14, (0.94, 1.37)); serum insulin (SRR=1.11, (0.75, 1.85)); c-peptide (SRR=1.00, (0.69, 1.46)) and adiponectin (SRR=1.16, (0.93, 1.46. An increase of 5 units in BMI was associated with post-menopausal breast cancer (SRR=1.12, 95% CI (1.08, 1.16)) but not at pre-menopausal ages (SRR=0.83, 95% CI (0.72, 0.95)). Serum insulin and c-peptide were associated with breast cancer at post-menopausal ages but not at pre-menopausal. For IGF-1, Hodge’s Standardised Mean Difference (HSMD) was calculated and there was no significant association with breast cancer (HSMD=0.026, 95% CI (-0.031, 0.084). The SRR for breast cancer among users of insulin glargine was 1.08 (0.98, 1.20) and was 0.92 (0.32, 2.65) when restricted to randomized trials. Among new users, the SRR for breast cancer was 1.09 (0.98, 1.21) and there was no trend of increasing breast cancer risk with increasing duration of use of glargine (β=0.04)(p=0.52). Risk of breast cancer in a prospective cohort declined with increasing follow-up, from 1.99 (1.31, 2.03) with two years of follow-up, to 1.60 (1.10, 2.32) with 3 years, 1.50 (1.10, 2.10) with four years and 1.18 (0.84, 1.66) with five years of follow-up. There is no reduction in risk of breast cancer associated with metformin use (SRR=0.96, 95% CI (0.85, 1.08)) even for the longest duration of use (SRR=0.94, 95% CI (0.81, 1.09)). Conclusions: An association between these two common diseases could have important implications for public health with common risk factors driving further increases in both diseases yet holding the tantalizing possibility for prevention of both. Overweight/Obesity and Physcal activity appear to be common links with the two diseases.
Race-based mortality as determined by intrinsic breast tumor subtype and p53 status.
Authors: Dookeran Keith A. , Dabbous Firas M , Booth Benjamin J 
Published: March 2020

e12519 Background: Race-based mortality differences have been reported for intrinsic breast tumor subtypes. p53 status has recently emerged as a marker of worse prognosis among African-American (AA) women with breast cancer; however, the impact of p53 status on mortality by specific subtype is not clear. Methods: Multivariable (age, stage and race adjusted) stratified (subtype and p53) analyses with proportional hazards regression models [hazard ratios (HR), 95% confidence intervals (CIs)] for all-cause mortality, in a cohort of 331 AA and 203 non-AA women (115 Hispanic, 88 non-Hispanic white) of lower socioeconomic status, consecutively treated for breast cancer at an urban hospital, with 60.4 months median follow-up, and known intrinsic subtype and p53 immunohistochemical status. Results: The Table shows the effect of p53 status and demonstrates increased mortality hazards across all subtype strata for AA women compared to non-AA. The largest change in hazards was observed for luminal A and HER2 subtype tumors with higher stage, but this pattern was also evident for lower stage tumors. Hazards of death were least increased across basal type tumors. Conclusions: Across each level of subtype, p53+ status increased the hazards of death in AA women with breast cancer. However, mortality hazards appeared most increased in women with luminal A and HER2 type tumors. [Table: see text]
Diabetes, insulin resistance, and metabolic syndrome in women at high risk for breast cancer.
Authors: Dumais Valerie , Verma Shailendra , Fontaine-Bisson Benedicte , Lumingu Julienne , Paquet Lise 
Published: March 2020

e12522 Background: Despite the growing body of research on diabetes (Db), insulin resistance (IR) and metabolic syndrome (MetS) in association with breast cancer, the prevalence of these metabolic conditions has yet to be explored in the high risk population. Delineating the numerous factors that contribute to these women’s risk is key in the management of this vulnerable population, especially when outlining potentially modifiable risk factors. The overall objective of this prospective study was to quantify the prevalence of Db, IR and MetS in women at high risk for breast cancer. Methods: Participants consisted of 100 Caucasian women above the age of 35 with an estimated 5yr risk of ≥1.7%. This criteria was met by (a) BRCA mutation carriers, (b) history of LCIS, (c) history of ADH, (d) history of mantle radiation, or (e) calculated 5yr risk of ≥1.7% using the Gail model. A comprehensive metabolic profile was obtained for each participant based on a questionnaire, fasting blood sample and biophysical measurements. The diagnostic criteria used for Db were those established by the Candian Practice Guidelines. The threshold for IR was a HOMA-IR value of 2.29. The MetS diagnostic criteria were those set by the IDF where 3 of 5 criteria from ↑waist circumference, ↑triglycerides, ↓HDL, HTN and hyperglycemia must be met. Results: The frequency (%) of Db (n=97), IR (n=96) and MetS (n=88) was 5(5), 17(18) and 29(33) respectively. Among the components of MetS, ↑waist circumference had the highest prevalence 60(68.2), followed by HTN 33(37.5), hyperglycemia 27(30.7), ↑triglycerides 23(26.1) and ↓HDL 22(29.7). There was a significant correlation observed between the Gail score and HDL (0.37, p<0.01), as well as systolic Bp (0.28, p<0.01). Conclusions: The prevalence of IR and MetS in this sample of women at high risk for breast cancer is considerably higher than the prevalence of these metabolic conditions in a similar population of average risk women, based on population data. This supports the significance and feasibility of an experimental study comparing the prevalence of IR and MetS in women at high risk and average risk for breast cancer. The prevalence of Db in this sample was comparable to the prevalence described in the general population.
Clinicopathologic characteristics of Lebanese patients under and over the age of 40 presenting with breast cancer at a single institution.
Authors: Shamseddine Ali , Abu Kar Sarah M , Alameddine Raafat , Saleh Ahmad , Temraz Sally , Mukherji Deborah , Majzoub Nadim , Dimassi Hani , Tfayli Arafat , Mahfouz Rami , Nemer Georges , Seoud Muhieddine A , El-hajj Ghada , Saghir Naji , Boulos Fouad 
Published: March 2020

e12525 Background: The objective of this study was to determine the clinicopathologic characteristics of Lebanese patients with breast cancer below 40 compared to those above 40 presenting to our institution. Methods: Using a cross-sectional study design, data were collected prospectively on a sample of 110 women newly diagnosed with breast cancer. Comparison between the groups was performed using Person Chi-square and Fishers exact test. Results: 28 patients were ≤ 40 years and 82 patients >40 years. 75% and 76.5% of patients above and below 40 years respectively presented with stage I or II disease, more patients above 40 presented with stage I compared to those below 40 (32.4% vs 8% respectively). 50% of the younger age group presented with a grade 3 tumor; however, more than the half of the older group presented with grade 1 or 2. The older age group had a higher incidence of concurrent lobular and intraductal carcinoma (0 vs 6.4%). The younger age group was more likely to present with nodal involvement (57.1% vs. 48.45 for younger and older age groups respectively). Similar proportions of the two age groups stained positive for cyclin B1, p53, and VEGFR. All patients stained positive for PDGFR. Mean value of Ki-67 was 21.8% and 24%in younger and older age groups respectively. These differences were not statistically significant. Methylene Tetrahydrofolate Reductase (MTHFR) single nuccleotide polymorphism (SNP) T677T was detected in 21% of the older group compared to 5% of the younger population. Stratified to age Vitamin D receptor (VDR) SNP ApaI A/A was found in similar proportion in both groups (35% and 33.3% in younger and older group) while 30% and 41.3 % carried the vitamin D receptor (SNP) BSMI b/b in younger and older group respectively. Conclusions: No significant differences in the clinicopathologic characteristics examined between patients younger or older than 40 years were found in this sample. Analysis of a larger sample size including BRCA gene mutation analysis is planned to determine differences between age groups and possibly explain the higher incidence of breast cancer in the younger age group in our population.