bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single institution retrospective study of the effect of starting doses in patients with ER-positive metastatic breast cancer on CDK 4/6 inhibitors.
Authors: Liu Wingsze , Olazagasti Coral , Lee Chung-Shien , Decina Taylor , Pappas Karalyn , Cheng Kit 
Published: May 2020

e13056 Background: CDK4/6 inhibitors (CDKi) have become part of standard of care in the treatment ER-positive, Her2Neu negative of metastatic breast cancer (MBC). Hematologic toxicity from CDKi are common which can lead to dose interruption or dose reduction. There is limited data to compare those who started on full dose and those who started on a reduced dose CDKi. We sought to investigate the impact of reduced starting dose of CDKis. Methods: We conducted a single institution retrospective study on patients (pts) who were treated with CDKi from 2015 to 2019. In this subgroup analysis, we sought to determine the percentage of pts that started on reduced dose CDKi. Pts who were started on reduced dose were compared to those started on standard FDA dose CDKi. Rates of hematologic toxicities, dose interruptions, further dose reductions, progression-free survival and overall survival were compared between the two groups. Data from absolute neutrophil count, hemoglobin and platelet count on Days 1 and 15 of the first 2 cycles were graded for hematologic toxicity according to CTCAE v 5.0. Results: Out of 220 pts, 175 (79.6%) pts started on standard starting dose CDKi and 45 (20.5%) pts started on reduced dose CDKi. 30.86% of pts on the standard dosing group and 28.9% of pts on the reduced starting dose group had a dose interruption. The association between starting dose and dose interruption is not statistically significant (p < 0.86). The estimated 12-month survival rate is 95% (95% CI: 89% - 97%) for the pts on standard dose CDKi and 85% (95% CI: 67% - 93%) for the group reduced dose group. The estimated 12-month progression-free survival rate is 72% (95% CI: 64% - 78%) for the standard dosing group and 35% (95% CI: 21% - 50%) for the reduced dose group. Conclusions: Our study showed a significant survival rate and progression-free survival rate difference between patients who were started on standard FDA starting dose compared to those started on reduced dose CDKi.
A prospective, open-label, multicenter, phase IV clinical study on the safety and efficacy of lobaplatin in the treatment of metastatic breast cancer.
Authors: Xu Binghe , Yan Min , Ouyang Quchang , Han Guohui , Cheng Ying , Wang Dewei , Li Ran , Zhao Da , Sun Tao , Bai Yuju , Yu Hao 
Published: May 2020

e13062 Background: Platinum-based chemotherapy is an important treatment for anthracycline- and taxane-resistant metastatic breast cancer(MBC), especially for triple-negative breast cancer(TNBC). Here, we presented the results of a phase IV clinical study of the third-generation platinum compound lobaplatin (LBP) in the treatment of MBC. Methods: Patients(Pts) diagnosed with MBC who had previously received chemotherapies containing anthracycline and/or taxane were recruited. The chemotherapy regimen was decided by the investigator but must include LBP. The primary endpoint was safety, the secondary study endpoints included PFS, OS, ORR, and DCR. Results: 1181 pts were enrolled from 34 research centers, 252 pts of them were TNBC. The main treatment regimens included LBP plus paclitaxel (134, 11.4%), LBP plus docetaxel(263,22.3%), LBP plus gemcitabine(235,19.9%) and LBP plus vinorelbine (404, 34.3%).The overall incidence of AE and grade III/IV(G3-4) incidence of AE were 95.00% and 58.10%, respectively. The most common AE were leukopenia (79.9%, G3-4: 39.5%), neutropenia(75.4%, G3-4: 43.8%), anemia(67.4%, G3-4: 17.8%), and thrombocytopenia(51.1%, G3-4: 17.8%). Creatinine clearance rate (Ccr) was the main influence factor for thrombocytopenia, the incidence of G3-4 thrombocytopenia in pts with Ccr < 60 ml/min were higher than that in pts with Ccr≥60 ml/min. Median follow-up was 36 months. The ORR and DCR were 36.8% and 76.9%, respectively. The mPFS and mOS were 5.5 months and 15.4 months, respectively. The efficacy of LBP combined with taxanes was significantly better than that of other regimens. Different sites of metastasis, ECOG score, clinical stage and age were the main factors influencing for efficacy. Conclusions: LBP-based regimens are effective and safe, and these regimens provide an alternatively treatment option for Chinese MBC pts. Clinical trial information: ChiCTR-ONC-13003471. Clinical trial information: ChiCTR-ONC-13003471 .
Development and validation of a nomogram for predicting survival of advanced breast cancer patients in China.
Authors: Lin Shaoyan , Mo Hongnan , Li Yiqun , Guan Xiuwen , Chen Yimeng , Wang Zijing , Yuan Peng , Wang Jiayu , Luo Yang , Fan Ying , Cai Ruigang , Li Qiao , Chen Shanshan , Zhang Pin , Li Qing , Ma Fei , Xu Binghe 
Published: May 2020

e13064 Background: The prognosis of patients with advanced breast cancer (ABC) varied according to different prognostic factors. This study aimed to establish a nomogram to predict the overall survival (OS) of ABC patients in China. Methods: Data from the China National Cancer Center database that recorded 4039 patients diagnosed with breast cancer between 1987 and 2019 were extracted and a total of 2263 ABC patients with complete relevant information were included in this study, which were further randomized 3:1 and divided into training ( n = 1706) and validation ( n = 557) cohorts. The nomogram was built based on independent predictors identified by univariate and multivariate analyses. Harrell′s concordance index (C-index) and calibration plots were used to assessed the discriminatory and predictive capacities of the nomogram. Results: With a median OS of 45.4 months, the 2-year and 3-year OS rates of ABC patients were 75.2% and 60.2%, respectively. Univariate and multivariate analyses found that age, Eastern Cooperative Oncology Group (ECOG) performance status, T-stage, N-stage, tumor subtype, the presence of distant lymph node (DLN)/liver/brain metastasis, local therapy, efficacy of first-line therapy and metastatic-free interval (MFI) were significantly associated with OS (all P < 0.05). These variables were incorporated into a nomogram to predict the 2-year and 3-year OS of ABC patients. The C-indexes of the nomogram were 0.700 (95% confidence interval [CI]: 0.683-0.717) and 0.686 (95% CI: 0.652-0.719) for the training and the validation sets, respectively. The calibration curves revealed satisfactory agreement between actual survival and nomogram prediction in both the internal and external validations. The nomogram was able to stratify patients into different risk groups. Conclusions: We developed and validated a nomogram that might serve as an efficient tool to provide individual prediction for ABC patients and guide the physicians to make personalized treatment decisions for individual ABC patients.
Effect of ARID1a oncogenic loss of function mutations on overall survival in metastatic breast cancer patients.
Authors: Mariotti Veronica , Soliman Hatem Hussein 
Published: May 2020

e13068 Background: ARID1a (AT Rich Interactive Domain 1A) is part of the SWI/SNF complex, which regulates gene transcription. Its inactivation has been shown to determine resistance to endocrine therapy via enrichment of basal-like gene expression features [Xu G., 2020]. We recently reported that ARID1a lower gene expression might be associated with worse overall survival (OS) [Mariotti V., 2019]. The aim of this study was to analyze the effect of ARID1a mutations on survival in metastatic breast cancer patients (pts). Methods: Breast cancer patients prospectively consented for inclusion in the ORIEN genomic database with known metastatic disease were analyzed using cBioPortal. Predicted biologic effect of mutations from RNASeq data was determined by OncoKB. OS was calculated from initial breast cancer diagnosis to death from any cause. OS analysis using Kaplan Meier and descriptive statistics were performed on SPSS. Results: We identified 644 pts with metastatic breast cancer. Of these, 88 (12.8%) pts harbored an ARID1a mutation. 62 (70.5%) mutations were missense (biologic effect unknown), the remaining 26 (29.5%) were oncogenic loss of function (OLF) changes (frame-shift, deletion, insertion, or nonsense). Median OS was significantly better in patients harboring missense mutations compared to OLF and wild type mutations [median OS 58.2 months (95% CI 44.5-71.8) with missense mutations vs 22.8 months (95% CI 10.8-34.7) with OLF mutations and 27.48 months (95% CI 24.5-30.3) with wild type]. Demographics, tumor features and chemotherapy use were generally equally distributed among the subgroups (table). Conclusions: In our study the median OS was worse in metastatic breast cancer pts harboring OFL ARID1a mutations compared to pts with wild type ARID1a or harboring missense ARID1a mutations. Further studies are warranted to assess how specific ARID1a mutations might affect survival in metastatic breast cancer pts. [Table: see text]
Effect of tailored and supervised therapeutic exercise in metastatic breast cancer patients: A prospective study.
Authors: Ruíz Sofía , Pajares Bella , Bermejo-Perez Maria-Jose , Roldán Jiménez Cristina , Cuesta Vargas Antonio , Alba Conejo Emilio 
Published: May 2020

e13075 Background: The safety, feasibility and benefit of physical activity is robust in adjuvant breast cancer, but as far as we know, there is little information on the feasibility and benefit of exercise in women with advanced breast cancer. The objective of our study is to analyze the feasibility and impact on fatigue, quality of life and functionality of an individualized, prospective and supervised exercise program in a group of patients with metastatic breast cancer. Methods: A prospective study on 30 metastatic breast cancer patients who were recruited as volunteers between February 2018 and April 2019 by Medical Oncologists from the Medical Oncology Unit at University Clinical Hospital Virgen de la Victoria (Malaga, Spain). Participants included in this study were patients aged between 34 and 71 years old and all had metastatic breast cancer, not amenable to curative treatment. The intervention was a twelve-week Therapeutic Exercise and Education Programme delivered by a physiotherapist. The intervention was preceded by a physical assessment of the musculoskeletal system. The outcomes were cancer-related fatigue, quality of life and functional outcomes (patient- reported and other measured by investigators). Results: Of the 30 patients initially recruited, only 11 of them completed the program with an attendance greater or equal to 17 sessions (75% of assistance). Most of patients who dropped (19), did it because of personal matters, not related to disease progression. Regarding patients who completed the completion of physical activity program (n = 11), the majority were treated on first line of treatment with hormonal receptors positive tumors and bone metastasis. After the intervention, no major changes were observed in cancer-related fatigue, quality of life and several patients-reported outcomes, although an improvement in functionality was observed, in investigator-measured parameters (30-STS and adapted burpees). Conclusions: Our study shows that a supervised and individualized tailored physical activity program in metastatic breast cancer patients is safe and feasible, although more studies are needed to analyse its impact on improving functional parameters, fatigue and quality of life.
Impact of absolute lymphocyte count on the efficacy of eribulin and capecitabine in patients with metastatic breast cancer.
Authors: Ueno Ayako , Maeda Reina , KIM Kyeongduk , Ito Mitsuya , Kawasaki Kensuke , Ohtani Shoichiro 
Published: May 2020

e13082 Background: In a phase 3 trial (Study 301), which compared eribulin and capecitabine for metastatic breast cancer did not show the superiority of one to the other on overall survival. Recently, a post-hoc analysis has revealed that efficacy of eribulin was greater in patients with high levels of absolute lymphocyte count (ALC), probably because the drug has immunologic mechanisms of action. Here we investigated whether the favorable impact of high ALC levels on the efficacy was specific to eribulin or shared with capecitabine. Methods: A total of 275 patients with metastatic breast cancer who were treated with eribulin (n = 125) or capecitabine (n = 150) in our hospital between July 2011–April 2019 were retrospectively analyzed. Progression-free survival (PFS) was compared between patients with higher ALC levels (≥1500/μL) and those with lower ALC levels ( < 1500/μL) in each treatment group. Then, we investigated how hazard ratio (HR) of PFS (eribulin vs. capecitabine) changed when we excluded patients with low ALC levels one by one; a scatter plot was made (X = cut-off value of ALC, Y = adjusted HR). PFS was compared by using the Cox proportional hazards model and covariates included age, hormonal and HER2 status, presence/absence of liver and other visceral metastasis, the number of involved organs and the number of previous chemotherapy regimens. Results: In eribulin group, PFS was significantly better in patients with higher ALC than those with lower ALC (adjusted HR, 0.50 [95% confidence interval (CI), 0.29–0.85]; p = .010). Contrarily, in capecitabine group, PFS was not significantly different between the two groups (adjusted HR, 0.86 [95% CI, 0.58–1.28], p = .456). According to the scatter plot, as the cut-off value of ALC (X) was increased, the hazard ratio of PFS (Y) changed biphasically, being almost flat when X was less than 1500, and a linear decrease when X was 1500 or more. Adjusted HR were (i) 1.07 [95% CI, 0.64–1.82], (ii) 0.79 [95% CI, 0.29–2.11] and (iii) 0.67 [95% CI, 0.18–2.41] when inclusion criteria of patients were (i) ALC ≥1500/μL, (ii) ALC ≥1900/μL and (iii) ALC ≥2200/μL, respectively. Conclusions: The efficacy of eribulin was significantly better in patients with higher ALC levels, whereas that of capecitabine was not significantly different. “The more, the better” relationship between ALC and the efficacy of eribulin (vs. capecitabine) was recognized when ALC was 1500/μL or more.
Recruitment and retention in a self-directed “walking” intervention: Feasibility study in women with metastatic breast cancer during active treatment.
Authors: Shachar Shlomit S. , Deal Allison Mary , Nyrop Kirsten A. , Damone Emily , Wagoner Chad William , Muss Hyman B. 
Published: May 2020

e13084 Background: Health related quality of life (HRQOL) and physical function are greatly impacted by the diagnosis and treatment of metastatic breast cancer (MBC). This study investigates the ability of women with MBC to engage in moderate walking during active treatment, with exercise monitored through a FitbitTM activity tracker. Methods: This is a single-site feasibility study of a home-based, self-directed physical activity intervention for women with MBC who could have had up to three lines of treatment. Questionnaires were completed at baseline, 12 weeks, and 24 weeks. Results: Sixty patients were consented, with mean age 55 (SD 11.1), 21% non-white, and 56% ECOG = 0. 36% were in their 3rd or 4th line of chemotherapy treatment. 65% had metastases to the bone, 46% to the lung, and 33% to the liver; mean number of metastasis sites was 2 (range 1 to 4). N = 52 completed all baseline measurements; N = 40 remained in the study at 3 months, and N = 29 at 6 months. Of the N = 31 (52%) lost to attrition, N = 6 were due to death, N = 5 due to deterioration, and N = 20 due to patient withdrawal from the study. Mean walking steps per day of at least 4000 was achieved in months 1, 2 and 3 by 41%, 50%, and 41% of participants. In months 4, 5 and 6, these percentages were 45%, 51% and 39%. On a scale from 1 = very confident to 10 = not at all confident about “continuing to walk or be physically active after completing the study”, confidence scores were 2.8 (SD 2.8) at 3 months and 2.9 (2.9) at 6 months. Conclusions: Forty-nine percent of women with MBC who signed up for a home-based walking program during active treatment were able to complete the 24-week intervention, with high proportions of these women walking more than 4000 steps per day. Moderate walking is feasible for women with MBC on active treatment.
Gemcitabine with carboplatin in metastatic breast cancer: Characterizing outcomes in a modern, real-world population.
Authors: Higgins Jordyn Paige , Lalonde Chloe , Byers Kristina F. , Davis Christine , Horne Kandra , Goyal Subir , Chen Zhengjia , Meisel Jane Lowe , Kramer Joan L. , Barbee Meagan Spencer 
Published: May 2020

e13085 Background: The specifics of the salvage regimen gemcitabine/carboplatin (G/C) in metastatic breast cancer (MBC) are not well-characterized and are limited to the clinical trial setting, which often excludes heavily pretreated patients with high disease burden and velocity. The primary objective of this study is to assess real-world outcomes in patients with MBC treated with G/C. Methods: A retrospective chart review was conducted on adults with MBC who received >1 dose of G/C at Emory Healthcare / Winship Cancer Institute from December 1, 2005 to April 30, 2019 (n = 109). Patients were stratified by receptor status (hormone receptor (HR), triple-negative (TN), and human epidermal growth factor receptor-2 (HER2)). Results: Patients were heavily pretreated (median 2 lines, range 0-11) and had extensive metastatic disease (median 3 sites, range 1-6). The median starting doses were carboplatin AUC 2 (range: 1.5-5) and gemcitabine 1000 mg/m2 (range 400-1100). The median cycle length was 21 days (range 14-28). The median progression-free survival (mPFS) was 3.7 months and median overall survival (mOS) was 7.7 months. OS at 24 months was 23.1%. Previous immunotherapy, radiation for palliation, or historical receipt of neoadjuvant/adjuvant cytotoxic therapy was significantly associated with improved survival outcomes, while possessing lung, liver, or bone metastases was significantly associated with worse survival outcomes. The presence of brain metastases did not correlate with outcomes. Side effect/intolerance led to dosing and scheduling adjustments in 38.5% and 49.5% of patients, respectively, and resulted in treatment discontinuation in 21% of patients. Hospitalization occurred in 51.4% of patients on treatment. Conclusions: G/C is a safe and effective regimen in real-world MBC patients regardless of receptor subtype. Even low doses of G/C may provide some CNS penetration and control. Improved survival outcomes associated with previous immunotherapy and radiation for palliation may be due to disease control or carry over effect and warrant further study. [Table: see text]
The role of circCNIH4 in the adipocyte's effects on metastasis of breast cancer cells.
Authors: Chen Xiu , Tang Jinhai 
Published: May 2020

e13086 Background: Obesity is associated with the risk of breast cancer(BCa) incidence and development. However, biological changes in obesity BCa individuals are still uncertain. Nowadays, circCNIH4, one of novel non-coding RNAs, was found to be a non-invasive biomarker in cancers. Methods: We verified the cancer-promoting role of obesity in BCa patients by comparing BMI indexes of 33 BCa and 44 benign tumor patients. Then we cocultured viscera adipose cells(HPA-v) and BCa cells(MCF-7/H and MDA-MB-231/H) to confirm the function of adipocytes on metastasis of BCa cells through wound healing, transwell assays. In vivo experiments were also performed. We analyzed the expression level of circCNIH4 in MCF-7/H, MDA-MB-231/H and different subtypes of BCa cells by quantitative polymerase chain reaction. Simultaneously, we identified inhibited effects of circCNIH4 on metastasis of BCa cells by wound healing, transwell assays and verified the location of circCNIH4 by FISH. Luciferase Assay was used to detect harbored miRNA. Rescue experiments were then applied. Results: We found the BMI of BCa patients(24.37±2.51) was much higher than benign patients(22.97±2.91). Metastasis of BCa cells were obviously promoted after in vitro and in vivo experiments. Then we found the expression of circCNIH4 in MCF-7/H and MDA-MB-231/H were down-regulated 0.71 and 0.52 than that in MCF-7 and MDA-MB-231. Also, circCNIH4 was positively correlated with less aggressive types of BCa cells. Overexpression of circCNIH4 in MDA-MB-231 could suppress cell invasion and migration, while silencing of it in MCF-7 promoted cell invasion and migration. The FISH assay demonstrated that circCNIH4 mainly located in the cytoplasm and might function as a “sponge” for miRNA. MiR-135b functioned as a tumor promoter gene from data of 93 BCa patients (HR = 2.27; 1.01 − 5.12), and it could be captured by circCNIH4 via luciferase and rescued assays. Conclusions: In this study, we revealed that BMI or viscera adipocytes could deteriorate prognosis of BCa and circCNIH4 could be a novel biomarker for non-invasive BCa. In details, circCNIH4 mainly suppressed the adipocyte's pro-metastasis effects on BCa by capturing miR-135b.
DNA and RNA next generation sequencing for personalizing cancer treatment: A single-center experience.
Authors: Rebollo Joseba , Sureda Manuel , González-Manzano Ramón , Martínez Elena Ma , Rostagno Roman , Mata Juan José , Monedero Elena , Ortega Jose , Brugarolas Antonio 
Published: May 2020

e13509 Background: Personalized multidrug therapies improve outcomes in patients with drug resistant cancer. For 8 years we have been using microarray-based gene expression profiling (360 procedures) to improve drug selection (Rebollo J et al, 2017; Sureda M et al, 2018). Recently, we have adopted Ion Torrent DNA and RNA Next Generation Sequencing (NGS) to improve the target detection ability. Methods: Since March 2018 DNA (95 analyses) and whole trancriptome RNA (78 analyses) NGS have been performed using Ion Torrent GeneStudio S5 System in fresh-frozen (RNA and DNA sequencing) and paraffin-embedded (DNA sequencing) biopsies obtained from tru-cut or surgical excision procedures from patients with metastatic cancer. Favourable chemotherapy drug profile, treatable (available inhibitory drugs) targets and potentially favourable immunologic signature have been investigated. Results: All biopsies were valid for DNA sequencing but in five patients were invalid (less than 30% viable tumor cells required) for RNA sequencing. Combined DNA and RNA sequencing have been studied in sixty patients with advanced cancer biopsies. Histologies have been NSCLC (12 patents), Breast (9), STS (6), NHL (4), NET (4), Pancreas (4), CRC (4), Ovary/Fallopian tube (3), Prostate (2), Cholangiocarcinoma (2), H&N (2), Esophagus, Bladder, Uterus, Melanoma, SCLC, Anal, Kidney and Cervix (1 each). Most of the patients had been previously treated with systemic therapies. Biopsies have been taken from Lymph nodes (18 patients), Liver (16), Soft Tissues (14), Lung (8), Peritoneum (3) and Adrenal Gland (1). RNA sequencing has predicted favourable chemotherapy drug profile (Median 3 drugs, Range 1-9) in 54 (90%) patients. In addition, treatable targets (Median 3 targets, Range 1-6) have been found in 40 (67%) patients. Favourable immunologic signature has been found in 22 (37%) patients. DNA sequencing has shown treatable (drug available) targets in 14 (23%) patients. In 12 (20%) patients, no targets have been found in any of the sequencing protocols (DNA and RNA). Conclusions: Tumor RNA and DNA sequencing provide potential useful information in personalized cancer treatment decision in a vast majority of advanced cancer patients independent of treatment status.