bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential protein expression profile in skin biopsies from patients with hand-foot syndrome who have benefited from topical heparin treatment.
Authors: Rodriguez-Garzotto Analia , Ruppen Isabel , Ximenez de Embun M. Pilar , Iglesias Lara , Gravalos Cristina , Agudo-Lopez Alba , Perez Carlos , Diaz Garcia Vanesa , Lopez-Martin Jose A. , Ciruelos Eva , Manso Luis , Mendiola Cesar , Agullo Ortuno M. Teresa , Cortes-Funes Hernan 
Published: March 2020

9641 Background: Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine (CAP), leading to significant morbidity in patients receiving this agent. Interruption or dose reduction of CAP is the only effective strategy. The purpose of our study is to define the pathophysiology and risk factors predictors of CAP-induced HFS. Previously, we had conducted a clinical trial in patients who developed HFS secondary to CAP. Topical heparin was administered in palms and soles of patients four times/day for three weeks (w), evidencing clinical improvement in 99% of patients. Methods: Paired-skin biopsies of palms at baseline and after 3w from 21 patients were obtained. An iTRAQ (isobaric tags for relative and absolute quantitation) proteomics approach was performed to identify molecular pathways associated with HFS reversion. Results: Comparative analysis between baseline and post-treatment skin samples identified 1876 proteins with high confidence (> 99%). The involvement of the identified proteins in biological networks served to characterize molecular pathways associated with HFS reversion. Conclusions: Several proteins identified in this study have a close relationship with keratinocyte terminal differentiation and keratinocyte intercellular strength. Also, we describe differential expression among proteins involved in inflammatory processes, skin immunity and cell death. In summary, our study not only served to uncover molecular mechanisms associated with HFS reversion, but also to reveal the biomarker role of several proteins in this syndrome. [Table: see text]
Inherited mutations in breast cancer genes in African American breast cancer patients revealed by targeted genomic capture and next generation sequencing.
Authors: Churpek Jane E. , Walsh Tom , Zheng Yonglan , Casadei Silvia , Thornton Anne M. , Lee Ming K. , Churpek Matthew , Huo Dezheng , Zvosec Cecilia , Liu Fang , Niu Qun , Zhang Jing , Fackenthal James , King Mary-Claire , Olopade Olufunmilayo I. 
Published: March 2020

CRA1501 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Trastuzumab associated cardiotoxicity: Who is at risk?
Authors: Abulkhair Omalkhair A. M. , Gasmelseed Ahmed , Al Otaibi Shabab 
Published: March 2020

e11518 Background: Trastuzumab is an important agent in the treatment of both adjuvant and metastatic breast cancer with known cardio toxicity. Cardio toxicity is defined as reduction in left ventricular ejection fraction (LVEF) of > 5% with signs and symptoms of heart failure (HF) or > 10% without such symptoms. Methods: Retrospective review of all breast cancer patients treated in King Abdulaziz Medical City with trastuzumab for adjuvant and metastatic setting from 2003 to 2012. 150 cases were identified, patients with good quality echocardiogram and base line LVEF > 55% were included (104). Patients had base line, then 3 monthly echocardiogram thereafter. Results: Studied patients showed that median age was 49 (43 - 58) years. There was a relevant decline in LVEF in 16 patients (15.38%), after mean exposure duration of 15 months. The study also revealed significant difference in EF decline between diabetic and non diabetic receiving herceptin (31.82% and 10.98% respectively, p-value 0.0213), and in 64.71% with hypercholesrolemia compared to 5.75% in those with normal cholesterol (p-value 0.0001). Conclusions: Given the limitations of this small retrospective review, we have shown that the prevalence of cardio toxicity in our patients is higher than published figures. Also, we have shown a significant correlation between diabetes, hyperlipidimia and cardio toxicity in trastuzumab treated patients. Such patients might need to be closely monitored for cardio toxicity.
Inflammatory markers in metastatic breast cancer.
Authors: Sahin Ugur , Petekkaya Hilbrahim , Gecmez Gizem , Babacan Taner , C. Roach Emir , Sarici Saim Furkan , Arslan Cagatay , Arik Zafer , Aksoy Sercan , Altundag Kadri 
Published: March 2020

e11545 Background: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The aim of this study is to find out the importance of serum markers as a prognostic indicator in metastatic breast cancer Methods: Women with metastatic breast cancer at the time of diagnosis were included. The study was conducted in Hacettepe University, Institute of Oncology, Department of Medical Oncology. Patient data were collected between December 2009 and January 2013. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value of < 0.05 was considered statistically significant. Results: Median follow-up time was 26 months. There were 29 mortalities due to disease progression during the follow up. The levels of serum albumin, ESR and LDH were not associated with a significant effect on overall survival. Among patients with a higher serum CRP estimated median survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p = 0.49). Among patients with higher serum ferritin levels estimated median survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p = 0.01). Among patients with higher serum beta-2 microglobulin estimated median survival was 28±8 months, compared to 84±57 months for normal levels (p<0.01). Conclusions: Serum CRP, ferritin and beta-2 microglobulin can be useful prognostic factors for overall survival among metastatic breast cancer patients.
Evaluation of factors related to late recurrence (later than 10 years after the primary treatment) in early breast cancer.
Authors: Nishimura Reiki , Osako Tomofumi , Nishiyama Yasuyuki , Tashima Rumiko , Nakano Masahiro , Fujisue Mamiko , Toyozumi Yasuo , Arima Nobuyuki 
Published: March 2020

e11557 Background: Breast cancer is associated with a relatively good prognosis and heterogeneity. Prognostic factors examined to date are related to early recurrence while those related to late recurrence and their countermeasures remain unclear. Therefore, we examined the factors related to late recurrence, later than 10 years after primary treatment, in early breast cancer. Methods: From 1980 to August 2012, 4774 patients who underwent primary treatment, including operation and estrogen and progesterone receptors (ER and PgR) measurement, were enrolled in this study. The patients were divided into two groups, those with a follow-up period within 10 years, and those (1323 patients) without any recurrence at 10 years but who continued follow-up examinations. Recurrence occurred in 711 patients within 10 years and occurred in 51 patients from ≥10 years. The items examined were tumor size, lymph node status, and biological markers such as ER, PgR, Ki-67 values, p53 and human epidermal growth factor receptor 2 (HER2) expressions. Results: The overall 10-year cumulative disease-free survival (DFS) rate was 79.5%, and the recurrence rate at ≥10 years was 5.8% (some cases had recurrence 20 years later). A multivariate analysis revealed that the factors related to late recurrence were positive nodes and PgR positive. This result differed from that for early recurrence, where the DFS rate was low in patients with ER/PgR negative, high Ki-67 index values and p53 overexpression. Conclusions: The PgR positivity and lymph node metastasis significantly correlated with late recurrence (later than 10 years after primary treatment) in early breast cancer. Therefore, it is important to evaluate appropriate measures such as treatment period and treatment regimen for hormone-sensitive (ER and/or PgR positive) patients. In addition, how to inform patients about the recurrence rate and recurrence time from the initial treatment, and the Informed Consent regarding the follow-up period and surveillance plan must be examined.
Meta-analysis of 59 gene expression based biomarker candidates predicting survival after tamoxifen treatment in breast cancer.
Authors: Gyorffy Balazs , Kormos Mate , Lanczky Andras , Mihaly Zsuzsanna 
Published: March 2020

e11564 Background: To date, three molecular markers (ER, PR and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Our aim was to validate new biomarker candidates predicting response to tamoxifen treatment by evaluating these in a meta-analysis of available microarray datasets with known treatment and follow-up. Methods: Biomarker candidates were identified in Pubmed 2007-2012 and in the 2010-2012 ASCO and SABCS abstracts. Breast cancer microarray datasets were downloaded from GEO and EGA. Of the biomarker candidates, only those identified or already validated in a clinical cohort were included. In the transcriptomic datasets, only patients with tamoxifen treatment for relapse-free survival and endocrine treatment for overall survival were eligible. The raw microarray data was re-processed and integrated into two databases. Relapse free survival (RFS) up to 5 years was used as endpoint in a ROC analysis in the GEO datasets. In the EGA dataset, Kaplan-Meier analysis was performed for overall survival (OS). Statistical significance was set at p<0.01. Results: The transcriptomic datasets included 667 GEO-based and 1208 EGA-based patient samples. All together 59 biomarker candidates were identified. Of these, the best performing genes were PGR (AUC=0.64, p=2.3E-07), MAPT (AUC=0.62, p=7.8E-05), SLC7A5 (AUC=0.62, p=9.2E-05) and TP53 (AUC=0.60, p=1.2E-03). Further genes significantly correlated to relapse-free survival include BTG2, HOXB7, DRG1, CXCL10, BCL2, TPM4, IGF1R and SMC3. Correlation to overall survival was significant for PGR (HR=0.67, p=1.7E-04), MAPT (HR=0.7, p=7.2E-04) and SLC7A5 (HR=1.6, p=1.6E-05). None of the remaining genes including ESR1 reached statistical significance for relapse-free survival. Conclusions: We validated two genes (MAPT and SLC7A5) as being capable to select those patients most likely benefit from tamoxifen treatment.
Breast cancer patients' risk perceptions and treatment values following surgical consult.
Authors: Kaiser Karen , Cameron Kenzie A. , Stolley Melinda , Bethke Kevin P. , Hansen Nora M. , Jeruss Jacqueline Sara , Clayman Marla L. , Khan Seema Ahsan 
Published: March 2020

e11572 Background: Contralateral breast cancer (CBC) is the most common second primary cancer in breast cancer patients. The 10-year risk of CBC for patients with locally invasive or intraductal disease is approximately 6%. However, a recent study reported that prior to surgical consult newly diagnosed breast cancer patients without a BRCA mutation estimated their 10-year CBC risk to be 31.4%. We sought to evaluate breast cancer patients’ perceived risk of future cancer and their treatment values following surgical consult. Methods: Women diagnosed with ductal carcinoma in-situ or stage I-III invasive breast cancer were interviewed in the period between surgical consult and surgical treatment. Participants completed the Perceived Risk Questionnaire (PRQ) and the Values Scale. The PRQ contains 5 questions to assess perceived likelihood of future cancer on a 5-point scale (1=not at all likely, 5=very likely). For each question, women also estimate the likelihood of cancer in the next 10 years as a percentage from 0 to 100. The Values Scale measures the importance of 11 treatment-related values (e.g., How important is it to you to keep your breast?) on a 10-point scale (1=not at all important, 10=very important). Results: Interviews were completed with 20 patients (mean age 54.7 years) without a known BRCA mutation. On the Values Scale, women identified minimizing the chance of cancer elsewhere in the body (mean=9.2), in the other breast (mean=9.1), and in the same breast (mean=8.8) as most important. Patients estimated their 10-year risk to be 13.6% for CBC, 14.2% for breast cancer appearing in the same breast, and 19.6% for cancer appearing elsewhere in the body. One-fourth of participants believed they faced at least a 50% chance of encountering breast cancer again in the next 10 years. Conclusions: Women in this study reported lower perceived risk of CBC than in a prior study of perceived risk prior to surgical consult, thus suggesting that the surgical consult may lead to a reduction in perceived risk. Nonetheless, participants’ estimated their 10-year risk of CBC to be twice the actual estimated risk. Our findings indicate a need for additional patient education about CBC risk.
D538G acquired mutation of estrogen receptor (ER) alpha: A novel mechanism of endocrine resistance in metastatic breast cancer.
Authors: Wolf Ido , Merenbakh Keren , Rubinek Tami , Soussan-Gutman Lior , Klein Baruch , Sarid David , Rizel Shulamith , Ben-Baruch Noa 
Published: March 2020

e11578 Background: Resistance to endocrine therapy occurs in virtually all patients with ER-positive metastatic breast cancer (MBC) and is attributed to various mechanisms including loss of ER expression, altered activity of coregulators and cross-talk between the ER and growth factor signaling pathways. To our knowledge, acquired mutations of the ER have not been described as mediating endocrine resistance to endocrine treatment. Methods: Deep sequencing of the ER was conducted, as part of a commercially available next-generation sequencing of 182 cancer-related genes, on samples obtained from 10 heavily pre-treated, endocrine resistant patients with ER positive MBC. In one patient, a sample obtained at diagnosis was also available. Mutated ER was cloned and overexpressed in breast cancer cells. Transcriptional activity was tested using estrogen response element (ERE)-Luciferase construct, effects on viability were tested using MTT assays and computerized modeling was used to assess structural effects. Results: A novel mutation resulting in substitution of aspartic acid at position 538 to glycine was identified in 4 of 10 samples. Moreover, in one case in which samples were available prior to and following development of resistance, the D538G mutation was noted only in the latter sample. Structural modeling indicated that the substitution leads to a conformational change in the ligand binding domain which prevents binding of either estrogen or tamoxifen and mimics the conformation of activated receptor. Experiments in cell lines indicated constitutive ligand-independent transcriptional activity of the mutated receptor. Overexpression of the receptor in MCF-7 cells enhanced proliferation and conferred resistance to treatment with tamoxifen and fulvestarnt. Conclusions: We report here a novel mutation D538G of the ER in human breast cancer and demonstrate its role in mediating resistance to endocrine treatment. Our study also indicates, for the first time, acquired mutation of the ER as a novel mechanism of endocrine resistance. Further studies on larger populations and on less selected patients are needed in order to assess the accurate frequency of this novel mutation.
Early stage “T2N0” breast cancer: Does it consist two different “T2” stages?
Authors: Arslan Cagatay , Sahin Ugur , Kizilarslanoglu Cemal , Solak Mustafa , Gullu Ibrahim Halil , Ozisik Yavuz , Altundag Kadri 
Published: March 2020

e11595 Background: Lymph node negative stage IIA early breast cancer (BC) patients (pts) according to TNM classification consists T2N0 tumors reprsenting a wide range of size (>2-5 cm). We aimed to compare clinicopathological features and prognosis of T2N0 stage pts with tumor size larger vs smaller than 4 cm. Methods: Data of 2200 BC pts followed between years 1998 and 2012 at our institute were analysed, retrospectively. pT2N0 stage BC pts (T:2 to 4,9 cm) were divided into 2 subgroups as 2 to 3,9 cm (T2a) and 4 to 4,9 cm (T2b). Clinicopathological features and survival analyses were evaluated. Results: There were 268 (80%) T2a and 65 (20%) T2b pts among T2N0 (n=333) population. All but 2 pts in T2a (99%) and all pts in T2b subgroups were female. Mean age of diagnosis was 50.8±11 and 46.2±10.1 years in T2a and T2b subgroups, respectively (p= 0.003). Number of premenopausal pts were higher in T2b (n=39, 60%) compared to T2a (n=100, 37%) subgroup (p= 0.003). There were no differences in histopathological subtypes, tumor grade, ER, PR, HER-2 status, adjuvant radiotherapy and chemotherapy regimens, -cycle numbers, endocrine, and trastuzumab treatments between T2a and T2b subgroups. Higher number of pts in T2a subgroup was treated with breast conserving surgery [110 (%41.2) vs 11 (%16.9)] and higher number of pts in T2b subgroup were treated with mastectomy [T2a= 158 (%58.8) vs T2b= 54 (%83.1)]. Disease recurrence was seen in 25 pts in T2a and 13 pts in T2b subgroups. Median progression free survival (PFS) could not be reached in T2a subgroup. Median PFS was 96.5 (min – max: 66 – 127) months in T2b subgroup (p= 0.02). There were no differences in PFS and number of events between goups when all pts analysed according to menopausal status and surgical treatment type. Overall survival data could not be analyzed due to small number of events (5 pts in T2a and 1 patient in T2b subgroups were died). Conclusions: T2N0 subgroup of stage IIA BC consists a wide range of tumor size between >2 to 4.9 cm. Pts with T2b (≥4 cm) tumors had shown worse prognosis compared to patients with T2a (<4cm) tumors and might be treated with more agressive adjuvant chemotherapy. This finding might be helpful for treatment decisions but must be evaluated in studies with larger number of pts.
A network meta-analysis assessing the comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer.
Authors: Nagayama Aiko , Hayashida Tetsu , Okabayashi Koji , Jinno Hiromitsu , Takahashi Maiko , Seki Tomoko , Matsumoto Akiko , Murata Takeshi , Kitagawa Yuko 
Published: March 2020

e11598 Background: The growing number of anti-HER2 agents suggests the eventual need for defining the optimal choice of neoadjuvant therapy for HER2-positive breast cancer. Multiple-treatments meta-analysis synthesizes information from a network of trials and combines direct and indirect evidence on the relative effectiveness. An indirect estimate of the benefit of A over B can be obtained by comparing trials of A v C with trials of B v C. In this study, we assessed the efficacy and safety of neoadjuvant therapy for HER2-positive breast cancer by conducting the direct and indirect comparisons from multiple RCTs. Methods: The primary outcome of the study was the number of the patients who achieved pathological complete response (pCR) defined as no invasive residual in breast or node. Secondary objectives were the number of patients who completed the treatment as planned and adverse events including diarrhea, neutropenia, cardiac events and skin disorder. Results: We identified 1047 articles by database search and 10 studies met our criteria. A total of 2247 patients in 7 different treatment arms were assessed; chemotherapy (CT) alone, CT with single or dual anti-HER2 agents and dual anti-HER2 agents without CT. Anti-HER2 agents evaluated were trastuzumab (T-mab), lapatinib, pertuzumab (P-mab). There was no significant difference between dual targeting treatment arms (CT + T-mab + lapatinib v CT + T-mab + P-mab, OR; 1.11, [0.42-2.86], p=0.41), however, lapatinib reduced the treatment completion mainly due to adverse events. Patients in dual targeting arms had significantly higher incidence of pCR than in other treatment arms. (CT + T-mab + P-mab v CT + T-mab, OR; 2.29, [1.02-5.02], p=0.02) Surface under the cumulative ranking probability curve (SUCRA) also indicated that CT + T-mab + P-mab had the highest probability of being the best treatment arm for pCR followed by CT + T-mab + lapatinib and CT + T-mab. Conclusions: This study provides evidence that combining two anti-HER2 agents with chemotherapy are the most effective treatment arms. Considering the cost and limited medical resources, CT + T-mab showed a well-balanced profile for efficacy, completion and safety.
Mesothelin expression and survival outcomes in triple-receptor negative breast cancer.
Authors: Parinyanitikul Napa , Blumenschein George R. , Wu Yun , Lei Xiudong , Chavez-Mac Gregor Mariana , Smart Melody L. , Gonzalez-Angulo Ana M. 
Published: March 2020

e12002 Background: Mesothelin is an ideal tumor-associated marker for the development of targeted therapy due to its limited expression in normal tissues. Identify the frequency of mesothelin expression in triple negative breast cancer may lead the path to customize the drug development in this lack of effective targeted subgroup. The aim of this study was to evaluate mesothelin expression in triple-negative breast cancer (TNBC) and its correlation with survival outcomes. Methods: Mesothelin expression was completed using immunohistochemistry on formalin fixed paraffin tumor sections, and quantified by H-score. An H-score >10 was considered positive. Patient’s characteristics were compared by mesothelin expression. Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics. Results: Median age was 52 years. Of the 109 TNBC, 37 (34%) were positive for mesothelin expression. There were no differences on patient/tumor characteristics by mesothelin expression with the exception of high frequency of lymphovascular space invasion in mesothelin-negative tumors (P=0.03). At a median follow up of 75.8 months 20 (18.3%) had experienced a recurrence and 22 (20.2%) had died. Five-year progression-free survival was 87% and 92% in patients with mesothelin-positive and mesothelin-negative tumors (P=0.43), and 5-year overall survival was 85% and 91% patients with mesothelin-positive and mesothelin-negative tumors (P=0.57), respectively. Mesothelin expression was not independently associated with PFS or OS in TNBC after adjustment for other patient and disease characteristics including grade, pathologic stage, lymphovascular invasion, and adjuvant chemotherapy survival outcomes. Conclusions: There was mesothelin expression in 34% of TNBC. No significant differences in the clinical characteristics by mesothelin expression with the exception of high lymphovascular invasion in mesothelin-negative tumors. Mesothelin expression did not correlate with survival outcomes in TNBC.