bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG for evaluation of “chemobrain.”
Authors: Moore Halle C. F. , Parsons Michael W. , Yue Guang H. , Rybicki Lisa A. , Siemionow Vlodek 
Published: March 2020

1076 Background: Cognitive impairment is a poorly understood and worrisome potential complication of adjuvant chemotherapy (CT). We sought to evaluate electroencephalography (EEG) as a means to measure neurophysiologic function in women receiving CT for early breast cancer. Methods: Women planning to undergo CT for operable breast cancer and age-similar controls were evaluated at baseline, during CT and at 1 year with neurophysiologic assessments. Testing included a brief fatigue inventory (BFI), brief mental fatigue assessment (BMF), Processing Speed Index (PSI) derived from Digit Symbol Coding and Symbol Search subtests of the Wechsler Adult Intelligence Scale, and a sustained elbow flexion physical task (PT). EEG recordings were obtained at rest and after the cognitive and physical tasks. Data were analyzed using repeated measures of analysis of variance. Results: Eight patient/control pairs completed baseline and on-treatment evaluations; 7 pairs also completed the 1 year assessment (1 pair withdrawn due to a second malignancy). Subjective mental fatigue measured by BMF is similar for patients and controls at baseline but BMF scores increase significantly during CT for patients relative to controls (p=0.033), recovering to no difference at one year. Differences in PSI are not observed between patients and controls or at the different time points. BFI scores are greater in patients at all 3 time points but endurance on the PT is no different from controls. During chemotherapy EEG total spectrum amplitudes in patients are greater than in controls at rest (p=0.05) and following both the cognitive (p<0.001) and physical (p<0.001) tasks. EEG activity prior to chemotherapy and at one year is not different between patients and controls. For patients but not controls EEG readings after the cognitive task demonstrate greater amplitude than pre-task readings during the time of CT treatment only (p=0.012) with a similar trend seen for the physical task (p=0.06). Conclusions: Patient-perceived mental and physical fatigue during chemotherapy correspond to significant changes in EEG brain activity patterns but not to cognitive testing or physical endurance testing. EEG may offer a sensitive means to measure alterations in brain function associated with CT.
Sequential treatment with epirubicin/cyclophosphamide, followed by docetaxel versus FEC120 in the adjuvant treatment of node-positive breast cancer patients: Final survival analysis of the German ADEBAR phase III study.
Authors: Janni Wolfgang , Harbeck Nadia , Sommer Harald Leo , Rack Brigitte Kathrin , Augustin Doris , Simon Wolfgang , Jueckstock Julia Kathrin , Wischnik Arthur , Annecke Katja , Friese Klaus , Kiechle Marion ,   SUCCESS Study Group
Published: March 2020

1081 Background: Based on meta-analytic evidence, taxane containing adjuvant chemotherapy has been established as standard treatment in breast cancer (BC). However, in the MA-21 study, adriamycin-cyclophosphamide, followed by paclitaxel was significantly inferior FEC120. We prospectively compared a sequential epirubicin-docetaxel chemotherapy regimen to FEC120. Methods: The ADEBAR study was a multicenter phase III trial (n=1502) to evaluate whether pts with > 3 axillary lymph node metastases BC benefit from a sequential anthracycline-docetaxel regimen (E90C–D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21d followed by 4 cycles docetaxel [D] 100mg/m2 q21d) compared to dose-intensive anthracycline-containing polychemotherapy (FE120C: 6 cycles E 60 mg/m² d 1+8, 5-FU 500mg/m² d 1+8 and C 75 mg/m² d 1-14, q4w). The observation time (median – 95%CI) was 49.5 (47.4 – 51.3) m. Results: Treatment was stopped prematurely in 3.7% of the pts in the E90C–D arm and in 8.0% in the FE120C arm due to toxicity (p=0.0009). Antibiotic treatment was given in 10.4% (E90C–D) vs. 19.7% (FE120C), G-CSF support in 39.2% vs 61.4 % and erythropoietin stimulation in 8.7% vs. 20.0%, respectively (p<0.0001). Haematological toxicity (leucopenia, neutropenic fever, thrombocytopenia, anemia) was significantly higher in the FEC-arm. At the time of the current analysis, 369 events of recurrence, were observed: 166 events in the FE120C group and 193 in the E90C–D group. The unadjusted hazard ratio (HR) was 0.877 (95 percent confidence interval, 0.722 to 1.065; p=0.3819, log-rank test). Overall survival in the two groups was not significantly different: (131 deaths with FEC vs. 134 with E90C–D (HR 0.996, 0.783-1.267, p=0.9691). Subgroup analyses, stratifying for tumor size, lymph node involvement, hormone receptor and HER2-neu status showed no significant difference between the two arms. Conclusions: Different toxicity profiles given, hematological toxicity in the FE120C group was more severe than in the E90C–D. In contrast to AC-P in earlier studies, EC-Doc provides a feasible and effective option to FEC120.
Participation in adjuvant clinical breast cancer trials: Is there a difference in survival compared to guideline adherent adjuvant treatment? A retrospective multicenter cohort study of 5,326 patients.
Authors: Wöckel Achim , Van Ewijk Reyn , Hoffmann Isabell , König Jochem , Kreienberg Rolf , Blettner Maria , Schwentner Lukas ,   BRENDA Study Group
Published: March 2020

1082 Background: Clinical trials (CT) usually compare a standard treatment regime versus innovative new substances or regimens. However participation in CT is available for only few patients and exclusion criteria is usually very strict. Therefore this study tries to answer the following questions: (1) Does participation in adjuvant CT improve survival in breast cancer (BC)? (2) Is there a difference in survival compared to guideline adherence and what is the role of the other treatments surrounding adjuvant breast cancer treatment? Methods: This German multi-center [17 participating hospitals all are certified as breast cancer centers] retrospective cohort study called BRENDA (BRENDA = quality of breast cancer care under evidence-based guidelines) included 5326 patients obtained from 1992 until 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). Results: 554 (10,4%) patients participated adjuvant clinical trials and 4772 (89,6%) not. There was a trend towards a significantly impaired RFS [p=0.17; HR=0.87 (95% CI: 0.71-1.06)] and OAS [p=0.65; HR=0.84 (95% CI: 0.65-1.09)] when comparing participants (PA) versus non-participants (NPA). When stratifying for guideline adherence (compared to PA-guideline conform in all adjuvant therapies) the outcome was not different in NPA-guideline adherent [RFS: p=0.13; HR=1.25 (95% CI: 0.94-1.67)] [OAS: p=0.83; HR=1.41 (95% CI: 0.96-2.06)]. However survival parameters were significantly impaired in non-guideline conform PA [RFS: p=0.005; HR=1.66 (95% CI: 1.16-2.38)] [OAS: p=0.01; HR=1.83 (95% CI: 1.15-2.92)] and non-guideline conform NPA [RFS: p>0,001; HR=1.70 (95% CI: 1.27-2.26)] [OAS: p=0.002; HR=1.82 (95% CI: 1.24-2.67)]. Conclusions: There is a strong association between guideline adherence in adjuvant treatment in BC and survival. PA in clinical trials trended to an improved survival, but only if guideline adherent treatment was applied. Patients who don`t have access to clinical seem to profit substantially of guideline adherent adjuvant treatment.
Reduction of ovarian reserve in young early breast cancer patients: First data of a prospective cohort trial.
Authors: Sanders Lea , Wenners Antonia Sophie , Koss Juliane , Schem Christian , Bauer Maret , Grambach Jana , Schaefer Fritz Werner , Schulz Ulrike , Jonat Walter , Schmutzler Andreas Gerd , Mundhenke Christoph 
Published: March 2020

1084 Background: Breast cancer is the most common malignancy in premenopausal women. Sideeffects of chemotherapy are well known nevertheless the precise effects on ovarian function are inadequately studied by now. Premenopausal women undergoing chemotherapy are at risk for symptoms of sexual hormone deficiency and impaired fertility. Searching for predictive parameters of ovarian reserve after chemotherapy this prospective cohort study has been set up. Methods: 36 young patients with primary breast cancer have been included in this trial after written consent (April 2010 to November 2011) and after the study was approved by the local review board. All women were premenopausal (< 46 years). They all received anthracycline based “A” neo- or adjuvant chemotherapy (as FEC) or combinations with taxanes “T” ( as TAC or FEC/Doc). Before and 6 and 12 months after initiation of chemotherapy age and chemotherapy related changes in hormone (LH, FSH, E2 and Anti-Müllerian hormone) levels, antral follicel count and amenorrhea as parameters of endocrine function and fertility were assessed.The additional impact of parity, BMI and nicotine use on ovarian reserve was also evaluated. Results: There is a correlation of antral follicle count before and 1 year after chemotherapy and a negative correlation of age and follicle count before and after chemotherapy (n.s.). This analysis shows that patients receiving “T” compared to those with “A” have a significant increase of LH (p=0.025) and FSH (mean:24 vs.59 IU/l, p=0.021) between visit 1 and 3. The type of chemotherapy has no influence on antral follicle count and AMH levels within the first 3 visits. BMI is negatively correlated with AMH at all time points (n.s.). BMI, nicotine abuse and age have no influence on the duration of amenorrhea, whereas patients with "T" showed 12 months of amenorrhea instead of 9 months in patients with "A" (n.s.). Conclusions: Our study will contribute to a better understanding and prediction of ovarian reserve of young early breast cancer patients undergoing chemotherapy. The 12 months follow up data suggest to offer fertility preserving measures before chemotherapy especially to patients planned for taxane containing chemotherapy.
Evaluation of overall survival (OS), progression-free survival (PFS), or time to progression (TTP) in systematic review of randomized clinical trials (RCT) in patients with metastatic breast cancer (MBC).
Authors: Mukonje Terence , Santana-Davila Rafael 
Published: March 2020

1089 Background: Limited data exists to establish if the introduction of newer agents has been associated with a trend towards an improved OS over time in women with MBC. Methods: Trough a computer-based systematic search of PubMed we identified RCT that treated patients with MBC published between 1980 and 2011. Trials that compared systemic chemotherapy for MBC, and reported a median OS were included. We excluded trials that use concomitant hormonal treatment, investigated only immunotherapy, or if they enrolled only responders to an initial regimen. The data abstracted included: year of publication, number of patients, regimens used, number of patient treated as 1st line vs. refractory patients, median PFS, TTP and OS. Linear regression analysis was used to establish trends. Results: An initial searched revealed 5485 publications, 134 RCT that enrolled 38,090 patients fulfilled our entry criteria and were included. First line therapy was studied in 99 trials and 35 evaluated mostly refractory patients. The use of adjuvant therapy has increased substantially, trials reported in the 1980’s had a mean of 0.07% of patients having had adjuvant chemotherapy compare to a mean of 48% in the last decade. Overall survival has significantly improved; the slope of the fitted line for first line clinical trials was 0.39 (p<0.001), which indicates a 0.39-month increase in median survival time per year. In trials of subsequent lines of therapy this slope was 0.19 (p=0.001). PFS or TTP was reported in 98 trials, interestingly in contrast to OS, this has not significantly changed, the slope for the fitted line has remained almost flat in both first line (0.002, p=0.97) and refractory trials (0.01, P=0.81). Conclusions: Our study is the first of its kind conducted in trials of patients with MBC. It shows that progress has been made in the last 3 decades OS in women affected with MBC, however the lack of change in PFS or TTP appears to indicate that the increase in OS is driven by a combination of newer agents, more subsequent lines of therapy being offered to patients and improved palliative care.
A study of sperm-associated antigen 5 (SPAG5) in predicting response to anthracycline (ATC)/platinum chemotherapies (CT) in breast (BC) and ovarian cancers (OVC).
Authors: Abdel-Fatah Tarek M. A. , Ball Graham , McArdle Stephanie , Johnson Catherine , Moseley Paul , Hosnii Shama , Green Andrew R. , Ellis Ian O. , Chan Stephen 
Published: March 2020

1098 Background: Recently TOP2A alteration was found to be a predictor for ATC-CT and our neural network analysis of BC gene expression array (GEA) data has revealed SPAG5 gene as a major hubs in both TOP2A and proliferation pathways. In this study the molecular and clinicopathological functions of SPAG5 was investigated in BC and OVC. Methods: (1) A series of 171 BC was evaluated for SPAG5 gene copy number (using aCGH) and mRNA expression (using GEA) which were validated in 5 independent databases. (2) The expression of SPAG5 protein was evaluated pre-clinically in BC and OVC cell lines and in both 40 normal breast tissues and a series of 1650 primary BC and was correlated to clinicopathological and other biomarkers. (3) The association between SPAG5 and response to CT was investigated in a) 350 ER negative BC treated with adjuvant ATC-CT, b) 250 BC treated with neoadjuvant (NEO-A)-ATC-CT, and c) 200 primary OVC treated with cisplatinum based adjuvant CT. Results: (1) 5% and 15% of the 171 BC showed amplification and gain of SPAG5 locus, respectively, at 17q11.2. SPAG5 mRNA expression displayed a significant correlation with its copy number (p< 0.0001). (2) 30% and 20% of ovarian and BC respectively, showed overexpression of SPAG5 protein (+). In BC, SPAG5+ at both mRNA and protein levels showed a significant association with aggressive phenotypes, high mitosis, ER-, high grade, p53 mutation and epithelial mesenchymal transition phenotypes (ps <0.0001). SPAG5 mRNA (+) was statistically associated with poor survivals (p<0.0001). (3) In ER- BC treated with adjuvant ATC-CT, SPAG5 negative (-)had 7-times higher risk of progression compared with SPRAG+ BC (p<0.0001). SPAG5+ BC received NEO-A-ATC based CT achieved 38% pathological complete response (pCR) vs. 6% of SPAG5- (p<0.0001). After controlling to other predictors for pCR, SPAG5 was an independent predictor (HR; 2.4; p=0.001). Similarly, SPAG5- OVCs were resistant to platinum (p<0.001) and independently associated with poor survival (p<0.001). Conclusions: SPAG5 is an important novel gene implicated in the survival of BC and OVC cells and its protein expression is an independent predictor for anthracycline/ cisplatinum CT.
Radiofrequency ablation (RFA) of breast cancer: A multicenter retrospective analysis.
Authors: Ito Toshikazu , Oura Shoji , Yamamoto Naohito , Nagamine Shinji , Takahashi Masato , Tanino Hirokazu , Yamamichi Noboru , Earashi Mitsuharu , Doihara Hiroyoshi , Imoto Shigeru , Mitsuyama Shoshu , Sonoo Hiroshi , Akazawa Kohei 
Published: March 2020

1119 Background: Local ablative therapy of breast cancer represents the next frontier in the minimally invasive breast-conservation treatment. We performed a retrospective study of ultrasound-guided percutaneous radiofrequency ablation (RFA) of breast cancers to determine safety and complication related to this treatment. Methods: Four hundred and ninety-seven patients with core biopsy proven breast carcinoma in 10 institutions of non-surgical ablaton study group underwent RFA without surgical excision were enrolled in this study. Results: Mean patient age was 54 years (range 22 - 92 years). Mean tumor size was 1.6 cm. Four hundred and twenty-five tumors ( 86 %) were ≤ 2 cm. The median follow-up period was 50 months (range 3 – 92 months). The mean required for ablation was 19 minutes (range, 4- 72 minutes), and the average temperature of the tumor after ablation was 91 degrees Celsius. The local recurrence rate after RFA was higher in tumors of negative estrogen receptor (8 of 78, 10%) than in tumors of positive estrogen receptor (17 of 437, 4%; p<0.05), and was higher in tumors of positive HER2/neu than in tumors of negative HER2/neu (14.9% vs. 3.2%; p<0.01). The local recurrence rate after RFA was higher in tumors of positive node than in tumors of negative node (9.8% vs. 3.6%), and was higher in tumors without irradiation than in tumors with irradiation (18.2% vs. 3.2%; p<0.001). The local recurrence rate after RFA was higher in tumors of > 2 cm (13 of 72, 18%) than in tumors of ≤ 2 cm (11 of 425, 3%; p<0.001). RFA-relating adverse events were observed in 17 patients of local pain, 14 patients of skin burn and 4 patients of retraction of nipple. Conclusions: RFA is considered to be a safe and promising minimally invasive treatment of small breast cancer ≤ 2 cm in diameter. Further studies are necessary to optimize the technique and evaluate its future role as local therapy for breast cancer.
Prospective outcomes trial of immediate, implant breast reconstruction using acellular dermal matrix (POBRAD Trial): Pilot series results.
Authors: Westbroek David , Douek Michael 
Published: March 2020

1131 Background: Acellular dermal matrices (ADM) are biological meshes of dermal origin (allo- or xenografts) stripped of all cellular components leaving a structurally intact and immunologically inert extracellular matrix. They are currently in use as adjunctive subdermal scaffolding during implant breast reconstruction to optimise aesthetic outcome. Despite current use in clinical practice there is no prospective data on their clinical efficacy, associated complication rates and cost-benefit analysis. These are the endpoints of our pilot cohort series, intended to provide baseline event rates to help power a multi-centre prospective, phase II, outcomes cohort study. Methods: From July 2011 to January 2012 and with our institution review board's approval - 20 consecutive patients undergoing immediate, implant breast reconstruction were prospectively accrued to the study. Primary endpoints: 30-day complication rates; Secondary endpoints: cosmetic outcome and cost-benefit analysis. Indications for mastectomy included therapeutic intent and/or risk reduction. The ADM used in all cases was SurgiMend PRS (TEI Bioscience Inc. Boston, MA). Results: Preliminary 30 day complication rates are in keeping with peer reviewed estimates for implant based breast reconstruction. Sub-set analysis of cosmetic outcome and cost-benefit ratio's are currently pending. In overview, ADM's appear to deliver the aesthetic benefit of autologous- implant cover (eg. latissimus dorsi myocutaneous flap) without the downside of donorsite morbidity and prolonged in-patient admission. Conclusions: This is to our knowledge the only prospectively accrued dataset seeking to critically evaluate the clinical efficacy, cost-benefit value and enhanced aesthetic utillity of ADMs (SurgiMend PRS) in the immediate breast reconstruction setting. The early results provide new evidence in support of the use ADMs in breast reconstruction and validate our intention to extend the study to a multicentre trial.
Estrogen plus progestin (E+P) and breast cancer incidence and mortality.
Authors: Chlebowski Rowan T. , Anderson Garnet L , Kuller Lewis H , Aragaki Aaron K , Manson JoAnn E , Stefanick Marcia L , Johnson Karen , Gass Margery , Lane Dorothy S , Ockene Judith , Sarto Gloria , Wactawski-Wende Jean , Rajkovic Aleksandar , Prentice Ross L ,   Women's Health Initiative
Published: March 2020

1501 Background: In the WHI clinical trial, E+P increased both breast cancer incidence and breast cancer mortality (JAMA 2010;304:1684). In contrast, breast cancers associated with E+P use in most observational studies have a more favorable prognosis. To address differences, a cohort of WHI Observational Study participants with characteristics similar to the WHI clinical trial was identified to examine E+P association with invasive breast cancer incidence and outcome. Methods: 41,449 postmenopausal women with no prior hysterectomy and mammogram negative for breast cancer < 2 years before who either were not hormone users (25,328) or were using E+P (16,121) were identified. Breast cancers were verified by centralized medical record review. Adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Additional analyses adjusted for breast cancer screening, censoring participants for incidence analyses who had a > 2 year interval without a mammogram. Results: After a mean (SD) follow-up 11.3 (3.1) years, 2,236 breast cancers were diagnosed. Breast cancer incidence was higher in E+P users (0.60% vs 0.42%, annualized rate, respectively: HR 1.55, 95% CI 1.41-1.70, P<0.001). Screening adjusted analyses had stronger breast cancer association (0.63% vs 0.39%, HR 1.72, 95% CI 1.54-1.93; P<0.001). Survival following breast cancer, measured from diagnosis date, was similar in E+P users and non-users (HR 0.95, 95% CI 0.74-1.23). Breast cancer mortality, analyzed from cohort entry date, are shown in the table. Conclusions: E+P use is associated with increased breast cancer incidence. As breast cancer prognosis following diagnosis on E+P is similar to that of nonusers, the higher incidence with E+P leads to increased breast cancer mortality. [Table: see text]
Long-term therapy with thiazolidinediones and the risk of bladder cancer: A cohort study.
Authors: Mamtani Ronac , Haynes Kevin , Bilker Warren B. , Vaughn David J. , Strom Brian L. , Glanz Karen , Lewis James D. 
Published: March 2020

1503 Background: The US Food and Drug Administration and other regulatory agencies recently warned prescribers that use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer. France and Germany removed the drug from their markets, although the rest of Europe did not. However, no information was available about the risk from alternative TZDs. We aimed to compare bladder cancer risk over time with use of TZDs relative to sulfonylureas (SUs), and between pioglitazone and rosiglitazone. Methods: We conducted a cohort study of patients with type 2 diabetes who initiated treatment with a TZD or SU using The Health Improvement Network (2000-2010), a UK general practitioner medical record database. Incident cancers within the database were identified. We computed hazard ratios (HRs) of bladder cancer for TZDs in comparison to the reference group of SU users. Results: There were 60 incident diagnoses of bladder cancer in the TZD cohort (n=18,459) and 137 in the SU cohort (n=41,396). There was no significant difference in bladder cancer risk between the cohorts (HR 0·93, [95% CI 0·68-1·29]), but most use was short-term use. In contrast, the risk of bladder cancer increased with increasing time since initiation of TZD versus SU therapy (HRs 1·15, 1·40, and 1·72 for 3-4, 4-5, and ≥ 5 years, respectively; P-trend=0·033). Bladder cancer risk also increased with increasing time since initiation of pioglitazone (P-trend<0·001) and rosiglitazone (P-trend=0·006). Direct comparison of pioglitazone to rosiglitazone did not demonstrate significant differences in cancer risk with increasing time since initiation (P-trend=0·12) or duration of therapy (P-trend=0·75). Conclusions: Long-term TZD therapy is associated with an increased risk of bladder cancer, which appears to be a class effect.