bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-14-21: Adjuvant chemotherapy-associated lipid changes in breast cancer patients: A retrospective analysis
Authors: He Tao , Wu Yunhao , Zhang Xinyi , Chen Jie 
Published: March 2020

Abstract
Background: Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy modalities remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare lipid level alterations among different chemotherapy modalities. Methods: We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy modalities: doxorubicin and cyclophosphamide followed by paclitaxel (AC-T); epirubicin and cyclophosphamide followed by paclitaxel (EC-T); cyclophosphamide and paclitaxel (TC); and fluorouracil, cyclophosphamide and epirubicin (FEC). Results: The levels of triglycerides (TGs), total cholesterol (TC) and low-density lipoprotein (LDL) were significantly elevated in patients who received chemotherapy (p&lt;0.01). With respect to different chemotherapy modalities, AC-T elevated the lipid profiles more than FEC in premenopausal patients (p&lt;0.05), while in postmenopausal patients, FEC had the smallest effects in terms of high-density lipoprotein (HDL) and LDL compared with the effects of other chemotherapy modalities (p&lt;0.05). In addition, premenopausal BC patients had a higher incidence of dyslipidaemia (18.84%) after chemotherapy than postmenopausal BC patients (12.27%). Moreover, after adjusting for multiple baseline covariates, AC-T chemotherapy modality was still statistically associated with a high level of TGs after chemotherapy. Conclusions: BC patients receiving chemotherapy may have a high risk of dyslipidaemia, but the effects vary with different chemotherapy modalities. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and to monitor serum lipids regularly during chemotherapy.Key words: Breast cancer; Adjuvant chemotherapy; Dyslipidaemia
Citation Format: Tao He, Yunhao Wu, Xinyi Zhang, Jie Chen. Adjuvant chemotherapy-associated lipid changes in breast cancer patients: A retrospective analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-21.
Abstract P2-15-13: A time-and-motion study of chemotherapy administration in metastatic breast cancer
Authors: Schwartzberg Lee , Chatterjee Debanjana , Knoth Russel , Gibbs Sarah N , Ahmed K Hamzah , Broder Michael S , Yermilov Irina 
Published: March 2020

Abstract
Background: Ordering and delivering chemotherapy is complex, impacting patient and caregiver quality of life. Metastatic breast cancer (mBC) patients receive intravenous chemotherapy with variable administration times and patient satisfaction may differ by session length. We investigated common chemotherapy agents for mBC through a time and motion analysis. Methods: We conducted a prospective, observational time-and-motion study of adult females with mBC receiving ≥ 2nd-line eribulin, vinorelbine (VI), or gemcitabine (GC) at a large community oncology clinic. An observer documented times events occurred (Table). Patients completed a satisfaction survey adapted from Agency for Healthcare Research and Quality’s cancer care survey and the Cancer Therapy Satisfaction Questionnaire. Event times were compared using t-test. Spearman’s rank correlation was used to test correlations between time and satisfaction. Results: 17 patients (11 eribulin, 6 VI/GC) comprising 31 observations (20 eribulin, 11 VI/GC) were included in the preliminary analysis. Patients were 65 years on average, 71% white, and 94% post-menopausal; all were HER-2-. Mean years since mBC diagnosis was lower for eribulin than VI/GC patients (1.7 vs 5.0, p&lt;0.009). Chemotherapy administration was shorter for eribulin patients (Table). 82% of patients were very satisfied with their cancer care experience; satisfaction did not correlate with event times. Conclusions: Eribulin administration time was significantly lower than VI/GC in mBC patients while maintaining similar satisfaction levels. These preliminary results demonstrate novel treatments for mBC can shorten treatment administration time while providing patient-centered, coordinated care. Table. Observation by event (mean minutes)
All observationsEribulin Vinorelbine/ GemcitabineP value *&lt;0.05Chair time (total time patient was in chair)7367840.174Chemotherapy ordered to chemotherapy end5449610.080Chemotherapy ordered to discharge6557740.111Chemotherapy arrived chair-side to chemotherapy end1510230.003*Chemotherapy arrived chair-side to discharge2620370.007*Chemotherapy administration (medication start to end)116200.001*
Citation Format: Lee Schwartzberg, Debanjana Chatterjee, Russel Knoth, Sarah N Gibbs, K Hamzah Ahmed, Michael S Broder, Irina Yermilov. A time-and-motion study of chemotherapy administration in metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-13.
Abstract P2-15-15: Evaluation of the efficacy and safety of the combination of Gemcitabine and Nedaplatin for patients with metastatic breast cancer
Authors: Yue Jian , Yuan Peng , Hu Nanlin , Si Yiran , Wang Xue 
Published: March 2020

Abstract
Background: Owing to the need for the effective and tolerable new regimens for the treatment of patients with metastatic breast cancer (MBC) previously treated with anthracyclines and/or taxanes, we aimed to assess the activity and safety of the gemcitabine plus nedaplatin combination chemotherapy.
Methods: Forty-five patients were enrolled. All the patients received gemcitabine and nedaplatin from November 2014 to February 2019.Gemcitabine 1000mg/m2 was administered on days 1 and 8. nedaplatin 60mg/m2 was given over 60mins on day 2 and 3. The primary end point was the overall response rate (ORR). Secondary objectives included overall survival (OS), progression-free survival (PFS), toxicity, and predictive factors.
Results: Patients received treatment for a median of four Cycles. One of the 45 patients achieved a complete response, but 21 achieved a partial response, for an overall response rate of 48.9(95% confidence interval,33.7-64.1%). The median overall survival time was 17 months and the median progression-free survival was 5.0 months. Grades 3-4 hematological toxicities include leukopenia in 22.2% of patients, neutropenia in 28.9%, thrombocytopenia in 17.6%. Grade 3-4 nonhematological toxicities included nausea and vomiting in 31.1% of patients. There were no treatment-related deaths.
Conclusion: The combination of gemcitabine and nedaplatin is an effective and tolerable treatment for MBC previously treated with anthracyclines and/or taxanes.
Table 1 Patient characteristicPatient characteristicNumber of patients45Age53(29-72)Molecular subtypeLuminal A9Luminal B14HER2 positive1Triple negative21
Table 2: Response rateNumber of patients(n=45)%Complete response12.2Partial response2146.7Stable disease1635.6Progressive disease715.6
Table 3 Non-hematological toxicityToxicityGrade≥3(%)1234Nausea/vomiting1512204.4Elevation of transaminase173000Alopecia63000
Table 4 Hematological toxicityToxicityGrade≥3(%)1234Leukopenia14159122.2Neutropenia13129428.9Thrombocytopenia124417.8Anemia224000
Figure 1 progression-free survival time
Figure 2 Overall survival time from the start of treatment with gemcitabine and nedaplatin.
Citation Format: Jian Yue, Peng Yuan, Nanlin Hu, Yiran Si, Xue Wang. Evaluation of the efficacy and safety of the combination of Gemcitabine and Nedaplatin for patients with metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-15.
Abstract P2-16-20: Treatment outcomes in triple negative breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67
Authors: Rapoport Bernardo Leon , Barnard-Tidy Jacqui , van Eeden Ronwyn , Smit Teresa , Nayler Simon , Benn Carol 
Published: March 2020

Abstract
Aim of study: The aim of this retrospective project is to evaluate the treatment outcomes including pathological complete response (pCR), time to progression and overall survival in patients (pts) treated with taxane, and/or anthracycline/alkylating agents based neoadjuvant chemotherapy (NAC).
Background: Ki-67 immunohistochemical determination is a widely used biomarker of cell proliferation in pts undergoing endocrine treatment for breast cancer. The role of Ki-67 in triple negative breast cancer (TNBC) pts undergoing NAC for early disease remains controversial. Pathological Complete Response following NAC has been proposed as a prognostic indicator of long-term outcome.
Methods: We analyzed retrospectively data on 86 pts with TNBC. Pathological complete response (pCR) was defined as the complete disappearance of the invasive cancer in the breast and absence of tumor in the axillary lymph nodes examined by axillary clearance. The purpose of this analysis was to investigate factors associated with combined pCR.
Results: There were 35 pCR’s (40.7%). At 2 years 82% of pts who attained a pCR were disease free compared to 67% of pts who did not attain a pCR (log rank test p &lt; 0.0117). On univariate analysis factors associated with higher combined pCR included primary tumor size (T1=84% vs T2 and T3 =50% of pts, chi2= 6.81, p&lt;0.03317), Ki67 (&gt;30=68% vs. eq or &lt; 30%= 18% of pts, p&lt;0.00020), age (&lt; than 50 =71% vs. equal or &gt;50 =44% of pts), tumor grade (1=88% vs. 2=60% vs. 3=44% of pts, chi2 = 6.2560 p&lt;0.04381) and stage (I= 89% vs. IIA=60% vs. IIB=46% vs. III=40% of pts, p&lt;0.01350). Factors not associated with a higher pCR included menopausal status, extranodal spread and lympho-vascular invasion. In a logistic regression model Ki-67 as a continuous variable (p&lt;0.012577) and age &lt; than 50 (p&lt;0.03318) retained its significance; while tumor size, stage of disease, tumor grade loss significance.
Conclusion: Ki67 and age are independent prognostic factors of pCR in pts with early TNBC undergoing NAC.
Citation Format: Bernardo Leon Rapoport, Jacqui Barnard-Tidy, Ronwyn van Eeden, Teresa Smit, Simon Nayler, Carol Benn. Treatment outcomes in triple negative breast cancer patients undergoing neoadjuvant chemotherapy. The importance of Ki-67 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-20.
Abstract P2-18-09: Effects of diet after early breast cancer treatment: Systematic review and meta-analysis of clinical trials
Authors: Träsel Henrique AV , Falcetta Frederico S , Almeida Fernando K , Falcetta Mariana RR , Rosa Daniela D 
Published: March 2020

Abstract
Purpose: Randomized clinical trials are inconclusive regarding the role of dietary interventions in anthropometric measurements, quality of life, and survival in breast cancer patients. Our aim was to conduct a systematic review and meta-analysis to assess the effects of diet on these outcomes in women who went through curative treatment of early-stage breast cancer.Methods: Pubmed, Embase, Cochrane Library were searched for randomized clinical trial comparing dietary interventions (individualized dietary counseling, prescription of a specific diet or other) with usual care in women that were treated for breast cancer. Primary outcomes were overall survival and disease-free survival, secondary outcomes were weight loss and change in body mass index.Results: We found 12 clinical trials eligible for analysis. Only two of them reported overall and disease-free survival, whereas six reported data for body mass index and four for weight. The HR for mortality and disease-free survival was 0.91 (95% CI 0.77-1,07, p=0.25) and 0.92 (CI 95% 0.79-1.08, p=0.31) for the intervention group compared to the control group, respectively. Diet intervention was associated with body mass index reduction in those subjects who received a specific diet instead of counseling or other types of intervention (-0.67 CI 95% -1.14 to -0.21). The weight did not differ between intervention and control groups.Conclusions: Despite increasing survival among breast cancer patients there is still a lack of prospective data regarding the effects of dietary interventions in this population. We found positive association between prescription of specific diets in terms of anthropometric measure, but neither difference in overall nor disease-free survival.
Citation Format: Henrique AV Träsel, Frederico S Falcetta, Fernando K Almeida, Mariana RR Falcetta, Daniela D Rosa. Effects of diet after early breast cancer treatment: Systematic review and meta-analysis of clinical trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-18-09.
Abstract P3-02-06: Tracing glucose catabolism in human triple negative breast cancer tumors
Authors: Ghergurovich Jonathan Michael , O’Shaughnessy Joyce , Levin Maren K , Killian Aaron , Hendricks William , Espina Virginia , Rabinowitz Joshua D 
Published: March 2020

Abstract
Triple negative breast cancer (TNBC) is an aggressive tumor type for which few targeted treatments exist. Altered tumor metabolism may provide novel diagnostic and therapeutic opportunities. Recent genetic analyses in TNBC demonstrate augmented expression of pathways related to glucose metabolism, including glycolysis, the pentose phosphate (PPP), and serine biosynthetic pathways. No studies, however, have directly probed how glucose is utilized by TNBCs in vivo. Here, we trace these metabolic fates by infusing TNBC patients with isotopically labeled 1,2-13C-glucose, a tracer that can determine which of these pathways predominate. Upon achieving stable tracer enrichment in serum, patient primary TNBC biopsies were collected and flash frozen. Subsequent analysis by liquid chromatography mass spectroscopy (LC-MS) revealed most TNBC tumors locally ferment glucose to lactate, with limited exchange of pyruvate/lactate with the systemic circulation. This contrasts with lung cancer, where pyruvate/lactate exchange is extensive. In addition, isotopic labeling patterns indicate that glycolysis dominates the PPP in terms of total flux. Nevertheless, ribose-phosphate for nucleotide synthesis consistently arises from the oxidative branch of the PPP. Furthermore, a subset of patients demonstrated high levels of de novo serine production. To better understand these observations, next generation sequencing (NGS) and reverse phase protein array (RPPA) analyses on adjacent biopsies from these patients are underway. Together, these findings provide the first comprehensive in vivo characterization of glucose metabolism in TNBC and raise the potential to use tracing to guide development of metabolic therapeutics.
Citation Format: Jonathan Michael Ghergurovich, Joyce O’Shaughnessy, Maren K Levin, Aaron Killian, William Hendricks, Virginia Espina, Joshua D Rabinowitz. Tracing glucose catabolism in human triple negative breast cancer tumors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-02-06.
Abstract P3-02-09: Vulnerabilities in glutamine metabolism define triple-negative from Luminal A breast cancer subsets
Authors: van Geldermalsen Michelle , Quek Lake-Ee , Turner Nigel , Balaban Seher , Hoy Andrew , Pang Angel , Guan Yi Fang , Wahi Kanu , Wang Qian , Holst Jeff 
Published: March 2020

Abstract
Although a nonessential amino acid in normal cells, the demand for glutamine is dramatically increased throughout malignant transformation to support increased metabolic demands; namely, provision of catabolic substrates for ATP production and anabolic substrates for the citric acid cycle and subsequent macromolecule biosynthesis, as well as potentiating the uptake of other critical amino acids by acting as an obligate exchange substrate. Elevated expression of glutamine metabolism-related genes, MYC-driven transcriptional events, and increased consumption and reliance on glutamine are all associated with aggressive breast cancers, including the high-risk triple-negative (TN) subtype. We recently showed that in breast cancer cells, glutamine uptake by the small neutral amino acid transporter, ASCT2, is required to sustain TN cell growth in vitro and in vivo. We therefore hypothesised that highly proliferative TN breast cancers that are sensitive to ASCT2 inhibition may have unique metabolic signatures that could be additionally exploited for therapeutic purposes. Using radiolabelled and stable isotope tracing methods, we analysed in detail glutamine catabolism and its conversion into various metabolic products such as tricarboxylic acid (TCA) cycle intermediates, lipids, nucleotides, and amino acids in human breast cancer cell lines in vitro and ex vivo. These analyses revealed distinct metabolic effects across cell lines representing different subtypes of breast cancer, both at baseline and when glutamine uptake was blocked in vitro by L-gamma-glutamyl-p-nitroanilide (GPNA), a pharmacological inhibitor of ASCT2. These data confirm a broad reliance on glutamine availability in TN breast cancers, where glutamine anapleurosis was significantly greater than in the Luminal A subtype. Analysis of gene expression data from the METABRIC and TCGA patient datasets and the CCLE cell line dataset showed a specific upregulation of multiple glutamine metabolism enzymes in TN breast cancer patient samples and cell lines compared to the Luminal A subtype. These data suggest a rewiring of glutamine metabolism in TN breast cancer that utilises their addiction to glutamine to fuel cell growth. Furthermore, these data provide an additional suite of glutamine metabolic enzymes that may be therapeutically targeted in the hard-to-treat TN breast cancer subset.
Citation Format: Michelle van Geldermalsen, Lake-Ee Quek, Nigel Turner, Seher Balaban, Andrew Hoy, Angel Pang, Yi Fang Guan, Kanu Wahi, Qian Wang, Jeff Holst. Vulnerabilities in glutamine metabolism define triple-negative from Luminal A breast cancer subsets [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-02-09.
Abstract P3-03-11: Notch inhibition promotes triple negative breast cancer growth
Authors: Saikumar Pothana , Singha Prajjal K , Venkatachalam Manjeri A 
Published: March 2020

Abstract
Notch1 and Transforming Growth Factor-beta (TGF-β) signaling pathways in cancer have a paradoxical roles as they were shown to have both tumor suppressive and tumor promoting activities. The interaction between these two signaling pathways in cancer progression was addressed in a systematic way. In these studies, we utilized primary human mammary epithelial cells (HMEC) and various triple negative breast cancer (TNBC) cells and examined the molecular cross-talk between TGF-β and Notch signaling pathways using biochemical, molecular and cell biology techniques. First, we noticed lower expression of Notch1 in most of the TNBC cells compared to normal cells. Second, most of these TNBC cells overexpressed TMEPAI (transmembrane prostate androgen induced) protein, which was shown to switch TGF-β from a tumor suppressor to a tumor promoter role in breast cancer. Surprisingly, treatment of TNBC cells with Notch inhibitors increased their growth rate both in the absence or presence of TGF-β. Moreover, Notch inhibition relieved the growth suppression by TGF-β in normal cells. Both normal and TNBC cells showed increased growth in the presence of Notch inhibitors with decreased TGF-β signaling activity. Normal cells that express very low levels of TMEPAI both at mRNA and protein levels, overexpressed TMEPAI protein in the presence of various Notch inhibitors, suggesting that Notch negatively regulates TMEPAI expression. Correspondingly, knockdown of TMEPAI in TNBC cell lines showed increased expression of Notch1 and Jagged 1 suggesting a negative regulation of Notch1 by TMEPAI. Consistent with these observations, TMEPAI, a known binding partner of E3 ligases, causes increased turnover of Notch1 protein. In fact, over expression of active Notch1 in MDA-MB-231 cells inhibited tumor cell growth both in vitro and in vivo. Our results clearly suggest that a crosstalk exists between TGF-β and Notch1 signaling through TMEPAI. Therefore, our studies clearly indicate that use of Notch inhibitors is contraindicated in triple negative breast cancer patients.
Citation Format: Pothana Saikumar, Prajjal K Singha, Manjeri A Venkatachalam. Notch inhibition promotes triple negative breast cancer growth [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-11.
Abstract P3-03-14: Screening strategies for Notch3-degradation-related E3 ligase in breast cancers
Authors: Liu Jing , Zhang Man-Li , Shen Jia-Xin , Xu Ya , Yuan Ming-Heng , Zhang Guo-Jun 
Published: March 2020

Abstract
BACKGROUND: The Notch pathway is very conserved and used iteratively during development and regulation of cell fates. Deregulation or loss of Notch signaling is associated with a wide range of human disorders, including breast cancer. It is accepted that ubiquitination events are linked to Notch receptors and their ligands where more than 10 E3-ligase and de-ubiquitination enzymes were implicated in this process. In this study, we attempt to apply a workflow to perform an E3-ligase RNAi screen focusing on the degradation system of Notch signaling pathway in breast cancer cells, hoping to further elaborate the pathogenesis of breast cancer and provide new ideas and schemes for its treatment.
MATERIALS AND METHODS: Breast cancer cell line MCF7 was treated with cycloheximide (CHX), an inhibitor of protein biosynthesis, to observe the half-life of Notch3 protein. Then a cell-based screening assay was utilized via a 4 × CSL-luc reporter gene, which reacted to a siRNA library targeting E3 ligases that when silenced inhibit proteasome function in Notch signaling pathway. Moreover, Western Blot and Real-Time PCR were conducted to measure various levels of Notch3 after over-expression of potential E3s. Immunoflourescence was checked for co-colonization of potential E3s and Notch3.
RESULTS: Since ubiquitination plays a major role in Notch, we performed a siRNA screen targeting human ubiquitin ligases in MCF7 cells. We quantified the activity of 4 × CSL-luc reporter gene as a read-out for Notch3 contents. From the screening results, we identified the APC/C ubiquitin ligase Cdh1 as a potential player in Notch3 degradation. Over-expressed Cdh1 led to decreased Notch3 levels in post-translational level. Moreover, Cdh1-triggered Notch3 led to a reversed accumulation when inhibited by proteasome inhibitor, MG132.
CONCLUSION: Taken together, the 4 × CSL-luc reporter system was effective for detecting the potential E3 ligase involved in the degradation of Notch3 through ubiquitination-proteasome system in breast cancer.
Citation Format: Jing Liu, Man-Li Zhang, Jia-Xin Shen, Ya Xu, Ming-Heng Yuan, Guo-Jun Zhang. Screening strategies for Notch3-degradation-related E3 ligase in breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-14.