bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of cardiovascular disease (CVD) risk factors and preventive care among U.S. cancer survivors.
Authors: Pearlstein Kevin A. , Hendrix Laura H. , Chen Ronald C. 
Published: March 2020

9592 Background: CVD is a major cause of mortality in cancer survivors. Prior claims-based studies suggested underutilization of preventive care in cancer survivors, but most CVD preventive care items are not available in claims data. We directly examined the prevalence of CVD risk factors and receipt of care in survivors compared to the non-cancer general population (control) using the National Health Interview Survey. Methods: 32,934 cancer survivors interviewed between 1999 and 2011 were matched to 65819 controls based on age, race, and history of CVD events (angina, myocardial infarction, stroke). Statistical analysis accounted for population sampling weight. Results: CVD risk factors were prevalent among cancer survivors (Table), and 33% continued to smoke. Primary care visits were reported more often among survivors compared to controls (83% vs 74%, p<0.001). A high proportion of survivors and controls received monitoring for diagnosed CVD risk factors, while rates of interventions to modify the risk factors were more modest. On multivariable logistic regression models, having a general doctor visit was associated with increased monitoring for all CVD risk factors examined (hypertension, hyperlipidemia, diabetes, obesity, smoking), but there was no significant difference between cancer vs control. Conclusions: Cancer survivors in the US receive comparable monitoring and interventions for CVD risk factors compared to non-cancer individuals. Survivorship care involving a general doctor was associated with improved monitoring of CVD risk factors. [Table: see text]
Do patients with cardiovascular diseases have earlier relapse in stage I-III non-small cell lung cancer?
Authors: Crescentini Robert M. , Reich Richard R. , Bardhan Pooja , Extermann Martine 
Published: March 2020

9603 Background: Diabetes mellitus (DM) has been reported to be an independent risk factor in the development of recurrence of NSCLC following treatment of early stage disease. We evaluated to see if there was a similar effect of cardiovascular disease in patients with newly diagnosed NSCLC. Methods: Using the Moffitt Cancer Center (MCC) databases, patients were identified who were treated for stage I, II and III NSCLC at MCC from 2001-2003. Charts were reviewed and descriptive data were recorded including histories of DM, coronary artery disease (CAD), hypertension, cerebrovascular disease and congestive heart failure (CHF). The use of aspirin and antihypertensive agents at the time of diagnosis were also recorded. Primary endpoint was disease free survival (DFS). Overall survival (OS) was a secondary endpoint. Kaplan Meier curves and Cox regression analyses were used for DFS and OS. Results: A total of707 patients were identified. Ninety-seven patients had DM, 158 had CAD, 396 had hypertension, 43 had cerebrovascular disease and 56 had CHF. DFS was worse in patients with DM (p<0.001, OR 0.63, 95% CI 0.50-0.80), CAD (p<0.001, OR 0.70, 95% CI 0.57-0.85), hypertension (p=0.016, OR 0.81, 95% CI 0.67-0.96), cerebrovascular disease (p=0.006, OR 0.62, 95% CI 0.45-0.87) and CHF (p<0.001, OR 0.56, 95% CI 0.42-0.75). Bivariate analysis showed that CAD, cerebrovascular disease and CHF were associated with shorter DFS independent of DM. OS was also worse in patients with DM (p<0.001, 95% CI 0.50-0.81), CAD (p<0.001, OR 0.62, 95% CI 0.51-0.78), hypertension (p=0.004, OR 0.77, 95% CI 0.64-0.92), cerebrovascular disease (p=0.02, OR 0.66, 95% CI 0.47-0.94) and CHF (p<0.001, OR 0.54, 95% CI 0.41-0.73). In patients with hypertension, there was an improvement in DFS (p=0.047, OR 1.35, 95% CI 1.004-1.819) for those treated with thiazide diuretics. There were no other statistically significant differences in patients based on antihypertensive regimens or aspirin use. Conclusions: DM,CAD, hypertension, cerebrovascular disease and CHF are associated with shorter DFS and worse overall prognosis in patients with non-metastatic NSCLC. CAD, cerebrovascular disease and CHF are associated with shorter DFS independent of DM.
Electro-acupuncture for joint pain related to aromatase inhibitors among breast cancer survivors: A randomized placebo-controlled trial.
Authors: Mao Jun J , Xie Sharon , Farrar John T , Stricker Carrie Tompkins , Bowman Marjorie , Bruner Deborah , DeMichele Angela 
Published: March 2020

9639 Background: Arthralgia is a common and debilitating symptom in a significant proportion of breast cancer patients receiving aromatase inhibitors (AIs). Methods: We conducted a randomized, placebo-controlled trial of electro-acupuncture compared to waitlist control (WLC) and sham acupuncture in postmenopausal women with breast cancer who self-attributed their arthralgia to taking AIs. Acupuncturists delivered ten treatments of tailored acupuncture with 2 Hz electro-stimulation via a TENS unit. Sham acupuncture used non-penetrating Streitberger needles at non-traditional acupuncture points and lacked electro-stimulation. The primary endpoint was pain severity measured by the Brief Pain Inventory (BPI) between electro-acupuncture and WLC at Week 8; durability of response at Week 12 and comparison of electro to sham acupuncture were secondary aims. Results: Sixty-seven patients were randomized to the three arms. The mean reduction in BPI pain severity was significantly greater in the electro-acupuncture group than WLC group at both Week 8 (-2.2 vs. -0.2 p=0.0004) and Week 12 (-2.4 vs. -0.2, p<0.0001). The BPI pain-related interference also improved significantly in the electro-acupuncture group compared to WLC group at Weeks 8 (-2.0 vs. +0.2, p=0.0006) and 12 (-2.1 vs. -0.1, p=0.0034). Sham acupuncture reduced pain severity (-2.3) and pain-related interference (-1.5) at Week 8 similar to electro-acupuncture (p= non-significant); however, the effect of sham acupuncture appeared to decrease at Week 12 for pain severity (-1.7) and pain-related inference (-1.3). Conclusions: Electro-acupuncture significantly improved AI-related arthralgia over “usual care” with clinically important and durable changes in symptoms. Treatment effects were similar between the electro and sham groups at Week 8, suggesting that a large component of acupuncture effect is mediated through the process of acupuncture delivery rather than the specificity of needle placement or needle penetration of skin. Research is needed to evaluate the long term effects of electro-acupuncture to improve AI-related arthralgia. Clinical trial information: NCT01013337.
Assessment of neratinib-resistance and cross-resistance in HER2-overexpressing breast cancer cells.
Authors: Breslin Susan , Corcoran Claire , Rani Sweta , Crown John , O'Driscoll Lorraine 
Published: March 2020

e11520 Background: While current therapies approved for HER2-overexpressing breast cancer (BC) treatment has led to advances in treatment of this BC subtype, issues of innate/acquired drug resistance are evolving. Neratinib (N) is an irreversible EGFR, HER2 and HER4 tyrosine kinase inhibitor currently in phase III clinical trials for BC treatment. We aimed to investigate the ability of BC cells to acquire resistance to N and the implications of this in terms of potential cross-resistance to other drugs and phenotypic changes in cells. Methods: Neratinib-resistant (NR) cell line variants were developed by exposing HER2-overexpressing BC cell lines, HCC1954 and SKBR3, to increasing concentrations of N over several months. Proliferation assays were used to establish IC50 values for N in parent and NR variants; as well as to assess possible cross-resistance to lapatinib (L), afatinib (A) and docetaxel (D). Phenotypic changes in NR cell variants were examined using invasion, migration and anoikis assays. IGF1R expression was determined using immunoblots. Results: HCC1954-NR and SKBR3-NR cell variants were 6.5±0.4 and 194±47 fold more resistant to neratinib than parent cells, respectively. Furthermore, HCC1954-NR variants were cross-resistant to afatinib (37±7.23 fold) and lapatinib (10±0.8 fold). SKBR3-NR variants were cross-resistant to afatinib by >163.3±22.7 fold (IC50 not reached at 9µM afatinib where, on average, 65.5 % cell growth is maintained) and lapatinib (162.3±22 fold). No cross-resistance to docetaxel was observed. Cells that have acquired N resistance are more invasive, migratory and resistant to anoikis than their parent controls. IGF1R expression is increased in NR cell variants compared to parent cells. Conclusions: Chronic exposure of BC cells to N results in acquired resistance to the drug. N resistance conferred cross-resistance to other HER2-targeting drugs and induced a more aggressive phenotype. Overexpression of IGF1R in NR variants suggested its role in the mechanism of N resistance.
Overall survival according to tumoral clusterin expression in breast cancer.
Authors: Mouillet Guillaume , Chaigneau Loic , Michy Thierry , Villanueva Cristian , Bazan Fernando , Almotlak Hamadi , Curtit Elsa , Cals Laurent , Montcuquet Philippe , Meneveau Nathalie , Algros Marie-Paule , Pivot Xavier B. 
Published: March 2020

e11579 Background: Clusterin (CLU) is a glycoprotein expressed constitutively in many tissues and involved in various physiopathological processes. Despite CLU expression is dysregulated in many types of cancer, the specific role of CLU in tumorigenesis remains unclear. The identification of several forms of the protein, with multiple roles is an explanation for these conflicting results. Cytoplasmic CLU (cCLU) has a role in breast tumorigenesis, cancer progression and is associated with breast cancer cell lines death in vitro. However contradictory data are reported about prognostic value of cCLU on survival and clinical progression. Our objective was to estimate patient’s overall survival (OS) according to the expression of cCLU. Methods: Histological and clinical data of 158 patients diagnosed with breast cancer were retrospectively recorded. Every patients were treated in a single French university hospital between 1993 and 2001. Histological samples had been reviewed to determine hormonal status, HER2 and clusterin expression. Immunohistochemical techniques were based on standards and recommendations applied at the time of analysis. Tumors were defined as cCLU positive (cCLU +) if its expression was superior to 10%. Overall Survival rates along with standard deviations were estimated using the Kaplan-Meier method. Differences in OS according to cCLU expression were tested for significance using the log-rank test. Results: Patients had a median age of 56 years (31 – 82 years). Among the 158 patients analyzed, cCLU was overexpressed in 31 patients (19.62%). The histopathologic and clinical characteristics were not statistically different according to clusterin expression even if a trend favouring less favourable tumoural characteristics were observed in cCLU positive tumour. The median follow-up was 14.1 years (11.3 - 19.3). In univariate analysis, cCLU overexpession were not related to OS (HR = 0.86; CI95%: 0.43 - 1.70). Ten-year OS was 76% (± 4) among patients with cCLU - tumors vs 77% (± 7) in patients with cCLU + tumor (p = 0.66). Conclusions: cCLU expression does not seem to be a pronostic factor of overall survival.
Anastrozole in combination with fulvestrant in the first line treatment of hormone receptor positive advanced breast cancer: A meta-analysis.
Authors: Tan Pui San , Haaland Benjamin , Montero Alberto J. , Lopes Gilberto 
Published: March 2020

e11591 Background: Emerging resistance to single agent aromatase inhibitors (AI) or fulvestrant as first line treatment for postmenopausal women with advanced hormonal receptor positive breast cancer calls for alternative therapeutic options. This meta-analysis studies the effectiveness of combination therapy with fulvestrant and an AI, as compared to an AI alone in first line treatment of postmenopausal patients with hormonal receptor positive relapsed or metastatic breast cancer. Methods: Literature search was performed using PubMed, Google Scholar, Embase, ASCO and ESMO to search for studies published during the last 10 years using relevant keywords. Two prospective randomized clinical trials were found to fulfill the search criteria for combination of fulvestrant + AI vs. AI alone (both studied anastrozole in combination with fulvestrant). Meta-estimates were calculated by combining study estimates using the DerSimonian and Laird random effects model. The linear mixed-effects model was used to generate 95% prediction intervals for study-specific hazard and odds ratios. Results: Pooled hazard ratio for progression free survival was 0.88 (95% CI 0.72-1.09, 95% prediction interval [PI] 0.65-1.21). Pooled HR for overall survival was 0.88 (95% CI 0.72-1.08, 95% PI 0.68-1.14). Pooled odds ratio for response rate was 1.13 (95% CI 0.79-1.63, 95% PI 0.78-1.65). Conclusions: Pooled results showed a small, non-statistically significant, improvement in progression-free and overall survival. These results do not support the use of combination therapy with fulvestrant and anastrozole in the first line treatment of postmenopausal patients with hormonal receptor positive relapsed or metastatic breast cancer.
Molecular pattern of breast cancer among a series of Egyptian patients.
Authors: Elmesidy Salah Eldeen , Elsherief Wessam , Abdelshafy Mohamed , Hammam Walid 
Published: March 2020

e11614 Background: Triple negative (TN) breast cancer has a bad prognosis. It is associated with a poor progression-free and overall survivals. Accordingly, we explored the outcome of different molecular subtypes among a series of Egyptian breast cancer patients. Methods: A total of 661 non-metastatic breast cancer patients' files with were reviewed from Kasr Al-Aini Center of Clinical Oncology and Nuclear Medicine of Cairo University between January 2005 and December 2010. Data were analyzed for age; menopausal status, tumour size, nodal status, pathological type, grade; estrogen status, progesterone status, and human epidermal growth factor receptor 2 (HER2) status. Disease free survival (DFS) was the primary end point. Results: The median age was 50 years. 50.4% of patients were premenopausal, 93.1% had invasive duct carcinoma, 93.3% had grade II tumours, 79.4% had early tumours (T1&T2), 70.4% had positive lymph nodes, 51.7% had luminal A subtype, 21.3% had luminal B, 10.2% had HER2-enriched and 16.6% had TN. Disease free survival after 3 years for each subtype was 87.8% for luminal A, 86% for luminal B, 69% for TN and 66% for HER2 (p= .008). The 3-year disease-free survival was significantly better for postmenopausal patients 92.1% as compared with premenopausal patients 80.1% (P= <0.001), with early tumours (T1&T2) 92.1% & 87.3% respectively as compared with advanced tumours (T3+T4) 80.1% (p= <0.001), LN negative (N0) 98.1% as compared with LN positive (N1+N2) 85.2% and (N3) 68% (p= <0.001), (ER) positive 90.2% as compared with (ER) negative 78.2% (p= <0.001), (PR) positive 90% as compared with (PR) negative 80.2% (p= 0.003), non TNBC 89.8% as compared with TN 72.1% (p= 0.012). The 3-year disease-free survival for TN patients who received adjuvant platinum-based chemotherapy was 46% and for those who received adjuvant non-platinum chemotherapy was 78% (p= 0.135). Conclusions: In our series of Egyptian patients luminal breast cancer subtypes (A and B) had the highest 3-year disease-free survival followed by TN then HER2-enriched type. Adjuvant platinum based chemotherapy had no impact on the 3-year disease-free survival when compared with non-platinum chemotherapy in TN patients.
Benzene-poly-carboxylic acids complex with Cis-diammineplatinum (II) dichloride (BP-C1), a novel anticancer agent, induces apoptosis in human breast cancer cells through caspase activation.
Authors: Fares Fuad , Fares Basem , Larsen Stig , Lindkair-Jensen Steen 
Published: March 2020

e12029 Background: Breast cancer is the most frequent malignancy in women in western countries and despite progress in the treatment options surgery, radiation, chemotherapy and hormonal therapy it is still the leading cause of cancer death. BP-C1 is a novel anti-cancer complex of benzol-polycarbonic acids with ammonium-platinum salt developed by Meabco ltd, Denmark. Methods: In the present study, the effect of BP-C1 on growth of human breast cancer cells, MCF7 and T47D, was studied. Cells were exposed to different doses of BP-C1, 100-1000 µg/ml, and cell viability, toxicity (LDH release), cell cycle, apoptosis, caspase activation and gene expression were examined. Results: No toxicity was observed. Exposure of the cells to BP-C1 for 48h, significantly (P<0.001) reduced cell viability by approxematly 90% with IC50 of 400 µg/ml. In cell cycle studies cells were accumulated in sub-G1 phase, which may indicate induction of apoptosis. Annexin 5 assay demonstrated that BP-C1 induces apoptosis of MCF-7 and T47D cell by 65% and 34%, respectively, after 48h of treatment. Detection of caspases by western blot analysis revealed that BP-C1 activates caspase 8 and caspase 9. Moreover, gene expression experiments following BP-C1 treatment and using the Applied Biosystems TaqMan Array Plates indicated that BP-C1 caused an increase in the the expression of pro-apoptotic genes; CASP8AP2, TNFRSF21, RELB, NFKB2, BIRC8 and FADD when compared to the expression level of the House keeping genes, HPRT1 and GAPDH. On the other hand, lower levels of mRNA transcripts of the inhibitory apoptotic genes; BCL2L2 and XIAP were detected. Conclusions: These results may indicate that BP-C1 reduced cell viability of human cancer cells by a unigue induction of apoptosis through activation of the extrinsic (death receptors) and the intrinsic (mitochondrion) apoptotic pathways. These findings may lead to the development of new therapeutic strategies for treatment of cancer using BP-C1 or analogs.
Searching for new genes responsible for unexplained hereditary breast and ovarian cancer patients.
Authors: Teule Alex , Quiles Francisco , Valdes-Mas Rafael , Pujana Miguel Angel , Salinas Monica , Feliubadalo Lidia , Capella Gabriel , Brunet Joan , Blanco Ignacio , Puente Xose S , Lazaro Conxi 
Published: March 2020

e12516 Background: About 10-20% of breast and ovarian cancer patients show family history of the disease. Germline mutations in the BRCA1 and BRCA2 genes are usually found in 20-25% of these cases, while the remaining ones are commonly known as BRCAX. Next generation sequencing (NGS) studies have the promise to expedite the identification of the genetic basis underlying BRCAX cases. Aim: To identify gene mutations associated with BRCAX cases by means of whole exome sequencing. Methods: Five selected BRCAX families with more than three affected individuals across at least three generations, and with an apparent dominant pattern of inheritance of the disease were selected in this study. All type of potential alterations of BRCA1/2and linkage to the corresponding loci were excluded in these families. For sequencing, libraries representing the whole exome of multiple affected individuals were obtained using the SureSelect Human All Exon 50 Mb Kit (Agilent) together with the Paired-End Sample Preparation Kit (Illumina) following manufacturers' protocols. Bioinformatics analysis to identify candidate variants present in each family was performed as previously described (PubMed ID: 21549337). Selected rare variants have been analyzed in a set of 288 controls and are currently being evaluated in 500 additional BRCAX cases. Results: By using the described workflow we have identified 16 candidate genes. They were selected based on the presence of rare missense variants that were not found in our control group, predicted as pathogenic using several algorithms (SIFT, PoplyPhen2, Condel and Mutation Taster). Currently, we are re-sequencing these genes in a set of BRCAX samples and complementarily performing loss-of-heterozigosity studies in tumor samples. Conclusions: Exome sequencing of 20 patients from 5 independent Spanish BRCAX families identified a list of putative new BRCAX genes that are currently in the process of validation. Identification of the genetic causes underlying breast and ovarian cancer in BRCAX families is paramount to perform genetic counseling and individual risk assessment in these patients.
Adverse events in non-AIDS-defining cancer patients receiving chemotherapy and combined antiretroviral therapy.
Authors: Sandhu Sonia , Cisak Kamila , Sreenivasappa Shylandra B. , Batra Kumar Kunnal , Gupta Shweta , Mullane Michael Russell , Blumetti Jennifer , Rubinstein Paul G. 
Published: March 2020

e12523 Background: From 1991 to 2005, the number of cases of non-AIDS defining cancers (NADC) rose from 3,192 to 10,059 in the USA. Studies have shown an improvement in survival for many HIV-associated malignancies in the post HAART era. Drug-drug interactions between HIV therapy and chemotherapy (CTX) are not well understood. HIV medications can inhibit or induce the cytochrome p450 system, modulating CTX clearance. To understand CTX-HIV medication interactions, we performed a retrospective analysis of all patients (pts) diagnosed with a solid NADC who took CTX with combined antiretroviral therapy (cART). Methods: 157 pts with solid NADC were identified via a computer search at County Hospital. Adverse events (AE) during CTX in pts taking cART were assessed by chart review and graded per the NCI Common Terminology Criteria. Statistics: A Fisher's exact test was used to examine the differences in AE incidence. Results: Patients who did not take cART in conjunction with, or did not require CTX, were excluded. The number of pts analyzed for anal cancer (n=25), lung carcinoma (n=9), breast (n=7), and head and neck carcinoma (HNSCC) (n=4) represents 94% of pts taking cART with CTX in our cohort. Interestingly, Forty-two pts (50%) never received cART during therapy. All pts with anal carcinoma were treated with mitomycin/5FU/radiotherapy. 46 % of the patients taking ritonavir-based cART (6 pts of 13) developed a G4 neutropenia versus 8% (1 pt of 12) taking non-ritonavir cART (p<0.07). Anemia all grades with ritonavir, 54%, versus non-ritonavir cART 16% (p<0.09). All grades neutropenia for lung carcinoma while taking ritonavir was 83% versus 33% while taking non-ritonavir cART. No other correlations were identified. In this cohort, 17 pts received platinum (37%), taxanes (n=5) (11%), anthracyclines (n=5) 11%, gemcitabine (n=2) (4%), and pemetrexed (n=1). No difference in AE was noted between any CTX class, AE, and cART. Conclusions: Ritonavirinduced a 38% increase in G4 neutropenia and anemia during treatment of anal carcinoma with mitomycin/5FU. More trials including HIV-associated cancer pts are needed to assess the role of cART when given in conjunction with CTX.