bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trastuzumab combined with doublet or single-agent chemotherapy as a first-line treatment for HER2-positive metastatic breast cancer.
Authors: Yu Yunfang , Wang Ying , Chen Kai , Fu Tuping , Yao Herui 
Published: September 2018

e12511 Background: To investigate the efficacy and safety of doublet vs. single-agent chemotherapy (CT) plus trastuzumab as first-line treatments for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). Methods: We searched for randomized clinical trials (RCTs) that investigated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcome measures for this analysis included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Meta-analyses and trial sequential analyses (TSA) were conducted. The study quality was evaluated using the GRADE framework. The PROSPERO registry number is CRD42016043766. Results: The results from four RCTs that included 1,044 participants were pooled. Moderate-quality evidence indicated that doublet CT+H better correlated with prolonged PFS (hazard ratio [HR] = 0.69, 95% confidence interval (CI) 0.63 to 0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88 to 0.92, P < 0.0001) than did single-agent CT+H; however, moderate-quality evidence indicated there was no significant difference between the two drug regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98 to 1.17, P = 0.157), as confirmed by TSA, which indicated that the cumulative Z-curve entered the futility area. There was moderate-quality evidence that the treatment-related grade 3 to 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000; number needed to treat to harm (NNTH) = 20), nausea/vomiting (RR = 4.26, P = 0.002; NNTH = 25), diarrhea (RR = 2.81, P = 0.002; NNTH = 25), and stomatitis (RR = 5.02, P= 0.003; NNTH = 25) were more frequent with doublet CT+H than single-agent CT+H. Conclusions: Doublet CT+H is associated with longer PFS and OS than single-agent CT+H when used as a first-line therapy for HER2-positive MBC.
Infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy.
Authors: Mortimer Joanne E. , Yuan Yuan , Jung Jae J , Stewart Daphne B. , Chung Samuel , Koehler Stephen , Cooper Jill , Kruper Laura , Wong Louise , Dadwal Sanjeet 
Published: September 2018

e12524 Background: We observed an increased incidence of severe skin and nail infections in HER2 positive patients whose treatment regimens included pertuzumab to trastuzumab-based chemotherapy; a previously unrecognized toxicity. Methods: We developed a registry for patients (pts.) who were identified by their treating physician to have severe skin/nail infections attributed to this dual HER2-directed treatment. A single infectious disease specialist (SD) oversaw the attribution of infection to drug or non-drug. Physicians were encouraged to assess quantitative immunoglobulins. Results: To date, 44 women were identified to have 62 individual episodes of infection, often at more than one site. Treatment was given as neoadjuvant therapy -24, as adjuvant therapy - 6, and for metastatic disease -14. The median age was 57 (Range 25-73); 24 received pertuzumab, trastuzumab, carboplatin, and docetaxel (PTCH); 22 pertuzumab, trastuzumab, and a taxane; 2 were on pertuzumab and trastuzumab alone. Folliculitis of the scalp, abdomen, chest wall and/or buttocks was observed in 31 patients; abscesses developed in 15;6 required surgical interventions. Paronychial infections involving one to 16 digits were observed in 6, 3 of whom required surgical intervention. With the exception of 2 pts, all had adequate WBCs. Cultures were obtained in 20 pts., and identified MSSA in 8, MRSA in 5, and Streptococcal species in 3. Two pts. with cellulitis had negative cultures; 1 pt. was cultured after initiation of antibiotics, and 1 pt. died of gram positive cocci sepsis on cycle 2 day 7 of PTCH. Her WBC on day 1 was 13.0, and she received pegfilgrastim on day 2. Immunoglobulins were found to be low in 16 of 29 (41%) women tested. In the absence of culture data, infections were managed with cephalexin, doxycycline, or topical antibiotics. The majority of patients continued on chemotherapy, but pertuzumab was deleted from the regimen in 2 pts. Conclusions: We continue to see a significant increase in gram positive invasive skin and nail infections in women with HER2 positive breast cancer treated with pertuzumab and trastuzumab-based regimens. Low levels of quantitative immunoglobulin in select patients suggest a possible mechanism.
Prediction of exemestane benefit in patients with advanced breast cancer based on diagnostic biopsy mRNA analysis.
Authors: Christensen Troels Dreier , Buhl Anna Sofie Kappel , Christensen Ib Jarle , Nelausen Knud Mejer , Balslev Eva , Knoop Ann Søegaard , Brix Eva Harder , Vestlev Peter Michael , Ejlertsen Bent , Kumler Iben , Luczak Adam , Langkjer Sven Tyge , Linnet Soeren , Jakobsen Erik , Bogovic Jurij Antonovic , Glavicic Vesna , Buhl Ulla Hald , Jensen Peter Buhl , Knudsen Steen , Nielsen Dorte 
Published: September 2018

e12532 Background: Exemestaneis a steroidal aromatase inhibitor used in the treatment of postmenopausal patients with estrogen receptor(ER)-positive adjuvant and advanced breast cancer. We aimed to determine the predictive value of a multigene mRNA-based mathematical algorithm (Drug Response Predictor (DRP)) for benefit of exemestane. The DRP is founded on measuring the full cancer transcriptome in sensitive and drug resistant cell lines compared with expression patterns in tumors and broadly validated in several studies (Wang et al. JNCI (2013) 105 (17): 1284-1291.) (Knudsen, S. et al. PLoS One (2014) 9(2): e87415.) (Christensen, TD et al. J Clin Oncol (2016) 34: suppl; abstr e12056.) (Kappel, IB et al. J Clin Oncol (2016) 34: suppl; abstr e20007.). Methods: Among 838 consecutive patients from a DBCG cohort with advanced breast cancer treated at 10 participating sites we identified 163 patients who between November 2008 and November 2015 initiated exemestane. All but one patient were ER-positive. Patients were evaluated every 3 to 4 months using CT scans and clinical examination. After patient informed consent mRNA was extracted and assayed on Affymetrix Gene Chip U133p2 arrays from formalin fixed paraffin embedded diagnostic biopsies. The primary endpoint was progression free survival (PFS). Analysis of the DRP’s ability to predict PFS was performed using a Cox regression model adjusted for treatment line. Results: Median PFS was 8.5 months. Of the 163 patients, 101 received prior adjuvant antihormone therapy and 60 did not. Data regarding adjuvant therapy was inaccessible for two patients. Hazard ratios for patients with predicted good vs. poor effect of exemestane are shown in the table. Conclusions: In a clinical setting, a mathematical algorithm using mRNA from a diagnostic biopsy can in patients unexposed to previous adjuvant endocrine therapy with statistical significance predict who will benefit from exemestane. [Table: see text]
Comparative efficacy with endocrine-based combination versus monotherapy among postmenopausal women with HR+/ HER2- metastatic breast cancer: A network meta-analysis.
Authors: Tang Derek , Ayyagari Rajeev , Patterson-Lomba Oscar , Zhou Zhou , Xie Jipan , Niravath Polly Ann 
Published: September 2018

e12535 Background: Endocrine-based therapies (ETs) are used to treat postmenopausal women with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) advanced breast cancer (ABC). This study synthesizes the available evidence on progression-free survival (PFS), overall response rate (ORR) and clinical benefit rate (CBR) with ETs, as monotherapy and in combination with targeted therapy (TT), in postmenopausal HR+/HER2- ABC using a mixed treatment comparison (MTC). Methods: A systematic literature review of Medline, EMBASE, Cochrane Library and key conferences (2013-2016) was performed to identify randomized clinical trials satisfying the following criteria: 1) included women with HR+/HER2- ABC, 2) included ET monotherapy and ET+TT combination arms, 3) reported PFS, ORR or CBR, and 4) was published in 2007 or later (when HER2 testing was standardized). Pairwise hazard ratios (HRs), relative risks (RR) and their corresponding 95% credible intervals (CrIs) were obtained via a Bayesian MTC. Efficacy was studied in first-line and aromatase inhibitor (AI)-failure (included patients who previously failed an AI or chemotherapy as first-line therapy) settings separately. ETs included letrozole, fulvestrant and exemestane, while ribociclib, palbociclib and everolimus were the TTs identified. Results: Three trials were eligible in the first setting for all three outcomes. TT+ET had significantly longer PFS vs. ET (HR = 0.56, 95% CrI 0.48-0.65), and also had significantly higher ORR (RR = 1.34, 1.17-1.51) and CBR vs. ET (RR = 1.17, 1.12-1.23). In the AI-failure setting, three trials were eligible for PFS, two for ORR, and none for CBR. TT+ET significantly improved PFS vs. ET (HR = 0.47, 0.41-0.53) and had significantly higher ORR vs. ET (RR = 3.52, 2.26-5.39). Conclusions: These results consistently indicate that the hazard of progression or death was approximately halved and that overall response and clinical benefit rates were significantly improved across patient settings for patients receiving TT+ET relative to ET monotherapy among postmenopausal women with HR+/HER2- ABC women.
The impact of stereotactic radiotherapy to metastatic site on systemic treatment decision in oligometastatic breast cancer patients.
Authors: Besen Ali Ayberk , Mertsoylu Huseyin , Kose Fatih , Yıldırım Berna , Gozel Sedat , Sedef Ali Murat , Ucar Aysenur , Onal Cem 
Published: September 2018

e12564 Background: Patients with oligometastatic disease achieve long-term survival with multimodality treatment strategies. However, little attention has been paid to the effect of adjusting systemic therapy after local therapy in clinical studies. The aim of this study was to investigate the effects of changing or continuing the same treatment regimen following local therapy on survival parameters. Methods: Out of 350 metastatic breast cancer patients, treated between 2012 and 2016, 43 patients (12%) with oligometastatic disease were included in our study. Oligometastasis was defined as < 5 metastatic sites in the same or different organs. Results: At a median follow-up of 32 months (7–53 months), 29 (67.4 %) patients had died. The one- and two-year overall survival (OS) rates were 95% and 78%, respectively, and the one- and two-year progression-free survival (PFS) rates were 77% and 51%, respectively. Following stereotactic body radiotherapy (SBRT) to oligometastatic sites, systemic treatment protocols were changed in 28 (65.1%) patients, while systemic treatment was continued unchanged in 15 (34.9%) patients. Changes to systemic treatment were significantly higher in patients with two organ metastases compared to patients with one organ metastasis ( p= 0.04). In the univariate analysis, estrogen receptor (ER) status and triple negative disease were significantly predictive of OS. The ER status and the number of metastatic organs were identified as significant predictors of PFS. In the multivariate analysis, only age emerged as a significant independent predictor of OS, while the number of initial organs involved and triple negative disease were significant factors for PFS. Conclusions: A hybrid treatment strategy is associated with higher survival rates in oligometastatic breast cancer patients. Post-SBRT systemic treatment change had no significant impact on OS and PFS in this study.
Serum phosphatidylcholine is lower among breast cancer patients on systemic chemotherapy.
Authors: Li Xin , Lim John , Kolatkar Anand , Welter Lisa , Waitman Kathryn , Hwang Eun-Sil Shelley , Lu Janice M. , Kuhn Peter , Nieva Jorge J. 
Published: September 2018

e12571 Background: Chemotherapy-induced cognitive impairment, also known as 'chemobrain', is widely recognized as a frequent adverse effect of chemotherapy, occurs in 10-40% of all cancer patients. Those cancer survivors suffer from poor concentration, memory, abstract reasoning, and motor dysfunction. The etiology is unclear. In our study, we analyzed the metabolite panels in breast cancer patients with vs. without chemotherapy trying to identify metabolic mediators of neurologic injury. Methods: We obtained plasma sample from 18 breast cancer patients, 9 received chemotherapy prior to blood drawn; while the other 9 had no systemic therapy. The plasma samples were sent for mass spectroscopy. Each metabolites level was normalized, and the two groups were compared in each metabolite by t-test with statistical significance corrected for multiple comparisons using the Holm-Sidak method. Results: We identified 57 amines and their metabolites; 106 carbohydrate related metabolites, and 228 lipid molecules. While amino acid, and carbohydrate did not show significant difference, phosphatidylcholine level in the chemotherapy treated group demonstrated lower level in the patients received chemotherapy. Among 59 phosphatidylcholine identified, 6 variants were significantly lower in the chemo group compare with non chemo group. Additionally the sum of all phosphatidylcholine variants was diminished in the chemotherapy treated patients compared with untreated controls. No other differences in plasma lipid levels were identified. Conclusions: Phosphatidylcholine is a major component of cell membranes and lipid rafts which are critical elements in nerve conduction. It also plays a role as the precursor to the neurotransmitter acetylcholine. The finding that phosphatidylcholine is significantly different between chemotherapy treated vs. the no chemotherapy group raises the possibility that lipid metabolism contributes to chemotherapy-induced cognitive impairment and further experiments are planned to explore this hypothesis.
Breast cancer molecular subtypes association with clinical outcomes and race.
Authors: Sadek Ramses F. , Zhang Li fang , Abdul Sater Houssein Talal 
Published: September 2018

e12575 Background: Breast Cancer (BC) has been classified into four subtypes: Luminal A (LABC), Luminal B (LBBC), Triple negative (TNBC) and HER2-enriched (HER2e). BC mortality in Black women is significantly higher than in Whites and Asians. BC in Blacks has been characterized by higher grade and later stage. Causes of the Black-White BC survival disparity have been investigated, including differences in: diagnostic stage, socioeconomics, and comorbidities. These have led researchers to investigate the differences in tumor molecular subtype and their association with clinical outcomes and races. Methods: This study used the Surveillance, Epidemiology, and End Results – 18 (SEER-18) Registries research data between 2010 and 2013 that included over 212,000 patients. Descriptive statistics, Odds ratios (OR) and 95%Confidence intervals (CI) were used to study the association between BC stage, grade, and mortality and BC molecular subtypes across different races. We employed Cox regression models to explore the race disparity in BC mortality before and after controlling for BC molecular subtype and other clinical and social factors. Results: TNBC had more high grade cancer compared to HER2e subtype (OR, 1.5; CI, 1.3 - 1.8), LBBC (OR, 4.5; CI, 4.0 - 5.0) and LABC (OR, 12.2; CI, 11.2 – 13.3) for Black. BC mortality was higher in TNBC subtype compared to HER2e subtype (OR, 1.3; CI, 1.1 - 1.6), LBBC (OR, 2.4; CI, 2.0 - 2.9), and LABC (OR, 2.8; CI, 2.4 – 3.2) for Blacks. Results are consistent for all races. HER2e subtype had more late cancer stage compare to LBBC (OR, 1.2; CI, 1.0 - 1.4), TNBC (OR, 1.4; CI, 1.2 - 1.6) and LABC (OR, 2.1; CI, 1.8 - 2.4) in Blacks with similar results in all races. BC mortality in Blacks was higher compare with Whites (HR, 1.9; CI, 1.8 - 2.0) and Asian (HR, 2.7; CI, 2.5 - 3.0). After controlling for cancer subtype and other factors in the Cox regression model, the corresponding HRs ware significantly decreased to 1.2 (CI, 1.1 -1.3) and 1.6 (9CI, 1.5 -1.8). Blacks have heighst percent in stage IV and grade higer grade of disease. Conclusions: Molecular subtypes of BC contribute differently to risks of late cancer stage, high cancer grade and BC specific mortality. These differences are consistent in all races. The molecular subtypes and other social and clinical factors may explain part of the BC mortality race disparity.
Triple negative breast cancer (TNBC): Analysis of age and stage distribution and survival between African American and Caucasian women in a predominant low-income population.
Authors: Tano Sheeba V. , Kavanaugh Mindie Michelle , Peddi Prakash , Mansour Richard P. , Shi Runhua , Burton Gary Von 
Published: September 2018

e12586 Background: Triple negative breast cancers (TNBC) represent roughly 15% of all breast cancer and are associated with decreased overall survival. A higher incidence of TNBC has been seen in younger and African American patients. We investigated the effect of age and race relative to outcomes of patients with TNBC seen at a state charity hospital system. Methods: This retrospective review identified 194 pts with TNBC diagnosed between 1993-2011 at LSUHSC-Shreveport, a state charity hospital. TNBC was defined as ER/PR both <1% and HER2neu not overexpressed by FISH analysis. The patient’s race, age at diagnosis, stage at diagnosis, treatment, relapse free survival (RFS), overall survival and survival following confirmed metastatic disease were analyzed. Results: There was no statistical difference in frequency of stage between groups. Although not statistically significant, there was a trend to worse RFS in AA and in young pts of both races. Younger age at diagnosis did have an inferior median survival as compared to older pts regardless of race or stage (p=0.0476). There was no difference in median survival following confirmation of metastatic disease between races (p=0.3574) or between age groups (p=0.8548); (median survival = 31 mos, 2.56-204 mos). Conclusions: In a predominantly low income patient population the incidence of TNBC was higher in the AA and in the young (age ≤ 50) as expected. There was no difference in stage or frequency within the populations. However, outcomes appeared to be worse in the younger pts and in AA patients with higher recurrence rate. Survival following first recurrence was similar regardless of age and race. Further analysis of etiologies for racial and age disparities is needed. [Table: see text]
Comparison of genomic and gene expression profile between cancer and healthy samples.
Authors: Papasotiriou Ioannis , Ntanovasilis Dimitrios , Apostolou Panagiotis 
Published: September 2018

e13001 Background: A variety of chromosomal aberrations underlie developmental abnormalities and cancer. Use of techniques such as microarrays provides an opportunity to perform gene expression analysis. A recent approach is the use of array based comparative genomic hybridization (aCGH) to detect genomic abnormalities in human tumors. The aim of this study is to compare genomic and gene expression profile between cancer patients and healthy individuals. Methods: DNA and RNA were isolated from peripheral blood mononuclear cells from 9 patients, with different types of cancer and 4 normal donors. aCGH (Agilent-60K) and gene expression microarrays (Microarrays Inc.-whole genome platform) were performed using commercial reference samples. Data were analyzed with Array-Pro analyzer and Cytogenomics software. Results: The aCGH data demonstrated the majority of gains and amplifications were observed in cancer samples, while the deletions and losses were higher in normal individuals. Among aberrations, common genes in both types of samples were detected. These genes included ACAD8, ACP1, B3GAT1, IDI1, IDI2, IGSF9B, IRX1, IRX2, JAM3, MYT1L, NTM, OPCML, PXDN, THYN1, TPO. However, there were abnormalities that included genes, which appeared only in cancer samples, like cadherins ( CDH11, CDH8 and CDH5) and EPHA5, while genes such as ACOX1, PTPRN2, TYMS and genes of zinc-finger proteins were observed only in normal samples. No statistical significant difference in gene expression, between cancer and normal samples, was observed. On the contrary, overexpression was observed in genes that were not detected in aCGH. Conclusions: Whereas it is acceptable that great achievements have been carried out in cancer field, the mechanism of tumorigenesis is not clear understood. The present study demonstrated that even though genomic aberrations exist, these are not always representative at gene expression level. However, the combination of both techniques could be used for more accurate and reliable data. This requires study in more samples including different cancer types so to be used at clinical level.
Implementation of reflexive genomic profiling in non-squamous NSCLC: Results of single center experience.
Authors: Brown Jacqueline T , Moore Andrew R , Reuss Joshua E , Simon Nicholas I , Gentzler Ryan D. , Hall Richard Delmar 
Published: September 2018

e13010 Background: Identification of oncogenic driver mutations (ODM) and targeted therapies have increased the number of treatment options for patients (pts) with non-squamous non-small cell lung cancer (ns-NSCLC). Different methods exist to detect ODM and there is no standard approach. This study examines the changes in detection of ODM over a 2-year period before and after implementing reflexive genomic testing using next generation sequencing (NGS) in January 2015. Methods: We retrospectively reviewed ns-NSCLC cases (stages I-IV) in 2014 and 2015 using the UVA Cancer Registry. We identified pts with pathologically-confirmed ns-NSCLC and reviewed any genotyping - single gene pyrosequencing, NGS, or FISH for gene rearrangements - within 90 days of pathologic confirmation. Comprehensive genomic profiling (CGP) was defined as both NGS and ALK/ROS1 FISH. Chi-square analyses were generated using SAS 9.4. Results: A total of 360 pts were included. 60% had genotyping while 19% underwent CGP. Mutations are summarized in the table below. From 2014 to 2015, genotyping increased from 50% to 69% (p<0.001), with CGP increasing from 2% to 48% of testing performed (p<0.001). Detection of oncogene driver mutations increased from 28% to 46% (p=0.009). Doubletons (pts with 2 driver mutations) increased from 0% to 5% (p=0.036). Conclusions: Reflexive CGP significantly increased the rate of detection of ODM at our center with results similar to previous studies. Previous studies detected low rates of doubleton mutations, perhaps due to lack of uniform NGS testing. Utilization of NGS may increase detection of doubleton mutations, for which further study is necessary to evaluate efficacy of targeted therapies. For centers without reflexive CGP, implementing this approach is likely to increase rates of ODM detection and expand treatment options. [Table: see text]