bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermal growth factor (EGF) gene polymorphism, gastroesophageal reflux disease (GERD), and esophageal adenocarcinoma (EAC) risk
Authors: Cheung W. Y. , Zhai R. , Kulke M. , Heist R. , Asomaning K. , Ma C. , Wang Z. , Su L. , Christiani D. , Liu G. 
Published: August 2020

11029 Background: Single nucleotide polymorphisms (SNPs) of key cancer genes, such as EGF A61G, are associated with an elevated risk of EAC, but the lack of full penetrance indicates that the effects of these SNPs on esophageal carcinogenesis are modified by additional genetic or environmental variables. Since GERD is an established risk factor for EAC, we evaluated whether the association between EGF polymorphism and EAC development is altered by the presence of GERD. Methods: EGF genotyping of DNA samples was performed and GERD history was collected for 309 EAC patients and 275 matched healthy controls. Associations between genotypes and EAC risk were examined with adjusted logistic regression. Genotype-GERD relationships were explored using analyses stratified by GERD history and joint effects models that considered severity and duration of GERD symptoms. Results: Baseline characteristics were comparable between cases and controls except that EGF variants (A/G or G/G) were more common (p=0.02) and GERD was more prevalent (p<0.001) in cases than in controls. When compared to the EGF wild type A/A genotype, the G/G variant was associated with an increased risk of EAC (OR 1.9; 95% CI, 1.2–3.0; p=0.007). Stratified analyses revealed that the G/G variant contributed to a substantial increase in EAC risk among individuals with GERD, but a slight decrease in risk for GERD-free individuals (see table). In the joint effects models, the odds of EAC was also highest for G/G patients who either experienced frequent GERD of more than once per week (OR 21.8; 95% CI, 5.1–94.0; p<0.001) or suffered GERD for longer than 15 years (OR 22.4; 95% CI, 6.5–77.6; p<0.001). There was a highly significant interaction between the G/G genotype and the presence of GERD (p<0.001). Conclusions: EGF A61G polymorphism exerts its effect on EAC susceptibility through an interaction with GERD. Performing EGF genotyping for patients with severe or longstanding GERD can help to identify individuals at the greatest risk of EAC. [Table: see text] No significant financial relationships to disclose.
TS-1 in patients with capecitabine-resistant breast cancer
Authors: Yamamoto D. , Yoshida H. , Iwase S. , Odagiri H. , Kitamura K. 
Published: August 2020

1103 Background: TS-1 is a novel oral anticancer drug, composed of tegafur, gimestat and otastat potassium in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-Fuorouracil. To evaluate the efficacy and safety of TS-1 in patients with capecitabine-resistant metastatic breast cancer (MBC). Methods: Forty patients with MBC who failed capecitabine-based chemotherapy, received TS-1 (100 mg/m2) at four centers. Resistance to capecitabine was defined as either progression of disease during treatment, failure to achieve regression of disease after at least four courses, or rapid recurrence after completion of therapy. Results: From January 2006 to May 2008, 40 pts were enrolled. Baseline characteristics of the pts were: median age 50 years (range 34–78), median ECOG PS 0 (range 0–2), and adequate bone marrow, renal, and hepatic functions. Median number of metastatic sites was 2 (range 1–5). The pts were evaluable for response and toxicity. Ten pts (25 %) achieved a partial response, 12 patients (30 %) patients had stable disease, and 18 (45 %) progressive disease. The median time to disease progression was 26.6 weeks. The most treatment-related adverse events were grade 1/2 in intensity. 7 pts experienced serious TS-1- related gastrointestinal disorder requiring dose modifications in 3 pts and treatment discontinuation in 4 pt. Further, interestingly, 6 of the 40 patients (15.0%) who received TS-1 did hand-foot syndrome (HFS), although 20 of the 40 patients (50.0%) who had received capecitabine, developed HFS. Conclusions: This study confirms that TS-1 achieves a high tumor control rate in pretreated MBC pts and is active in patients with capecitabine-resistant breast cancer. Response rates were comparable to or better than those seen with other therapies for patients with capecitabine-resistant MBC. TS-1 should be considered the reference treatment in this setting based on consistently high efficacy and good tolerability. No significant financial relationships to disclose.
Expression and epigenetic silencing of ECRG4gene in breast cancer
Authors: Fei F. , Shao Z. 
Published: August 2020

11046 Previous whole-genome expression array studies in our laboratory had shown the expression of ECRG4 (esophageal cancer related gene 4) was significantly down-regulated in primary breast cancer. The present study was undertaken to investigate the expression and epigenetic regulation ofECRG4in human breast cancer cell lines and primary carcinomas. Here we showed that the expression ofECRG4, as measured by quantitative reverse transcription-PCR, was noticeably increased in 3 methylated breast cancer cell lines (MDA-MB-435, Bcap-37, MCF-7), after treated with 5-aza-2’-deoxycytidine - a demethylation agent. Analysis from 16 paired tissue samples revealed expression of ECRG4 was significantly reverse-correlated with methylation (Spearman correlation coefficient r=-0.419, P=0.017). Analysis of 67 additional samples showed that the ECRG4 CpGs island was in high methylation level in 59.7% of cancer tissues compared with 14.9% in tumor adjacent tissues,with an odds ratio of 3.393 (95% CI, 1.912–6.021,P=8.39E-8). And patients with high methylation level had a higher tumor grade. 90% samples were high methylation levels in grade III vs. 50% in grade I-II (95% CI, 1.063–76.213, P=0.033). In conclusion, the inactivation of ECRG4 gene by hypermethylation appears to be a frequent molecular event in development of primary breast cancer and may be involved in the carcinogenesis of this cancer. No significant financial relationships to disclose.
Association of baseline c-reactive protein with incident cancer and survival in cancer patients
Authors: Allin K. H. , Bojesen S. E. , Nordestgaard B. G. 
Published: August 2020

11052 Background: We tested the hypothesis that baseline plasma levels of C-reactive protein (CRP) associate with risk of incident cancer in the general population, and early death in cancer patients. Methods: 10,408 individuals from the Danish general population, who had CRP measured at baseline, were followed for up to 16 years; 1,624 developed cancer and of these, 998 died during follow-up. Follow-up was 100% complete. We excluded individuals with a cancer diagnosis at baseline. Results: Baseline CRP levels >3 vs. <1 mg/L were associated with multifactorially adjusted hazard ratios of 1.3 (95% CI, 1.0–1.6) for cancer of any type, of 2.2 (1.0–4.6) for lung cancer, of 1.9 (0.8–4.6) for colorectal cancer, and of 0.7 (0.4–1.4) for breast cancer. Corresponding hazard ratios for the highest vs. the lowest quintile of baseline CRP levels were 1.3 (1.0–1.6), 2.1 (1.2–3.8), 1.7 (0.8–3.2), and 0.9 (0.5–1.7), respectively. Multifactorially adjusted hazard ratios for early death in cancer patients were 1.8 (1.2–2.7) for CRP >3 vs. <1 mg/L and 1.4 (1.1–1.7) for the highest vs. the lowest quintile. Elevated CRP levels associated with early death in cancer patients with localized disease, but not in cancer patients with metastases (interaction; P=.03). Conclusions: Elevated levels of CRP in cancer-free individuals are associated with increased risk of cancer of any type, of lung cancer, and possibly of colorectal cancer. Moreover, elevated levels of baseline CRP associate with early death after a diagnosis of any cancer, particularly in patients without metastases. No significant financial relationships to disclose.
The differences in rate and duration of complete remission between HER2-positive and HER2-negative inflammatory breast carcinoma
Authors: Kolarevic D. , Tomasevic Z. , Andjelic Dekic N. , Milosevic S. , Jelic S. 
Published: August 2020

1106 Background: Inflammatory breast carcinoma (IBC) is rare but aggressive form of breast cancer. Up to 38% of IBC are HER-2+. According to literature, complete remission (CR) can be achived in more than 50% of patients with combinatination of chemotherapy and trastuzumab. However, trastuzumab is still not available in all countries. The aim of this study was to evaluate the rate and duration of CR to induction chemotherapy alone, without trastuzumab, in HER-2+ and HER-2- IBC pts and compare our results to literature data. Methods: The data were analized for 3,452 breast carcinoma patients registered at the Institute for Oncology and Radiology of Serbia (IORS) during one year. Among them, 281 pts had IBC, defined as pathologically confirmed skin lymphangiosis or BC with classical clinical signs of cancer mastitis. Responses have been evaluated clinically and by mammography after every 3–4 cycles of chemotherapy. CR was estimated as a complete disappearance of previously palpable breast tumour; no clinical and mammography signs of cancer mastitis; no enlarged regional lymph nodes and disappearance of all metastatic sites in stage IV. HER-2 status (IHC, Dako) was assessed in 88 patients (70.9%) and 25/88 (28.4%) were HER-2 3+. Results: We investigated 124 IBC pts with complete medical records. The overall incidence of IBC was 8.1%. Median age at diagnosis was 59 (ranges 35–81). The rate of CR is evaluated separately in subset of HER2+ and HER2- IBC. 100 pts received FAC induction chemotherapy (median number of cycles was 6) and remainder received CMF regimen (median number of cycles was 5), trastuzumab none. Only seven pts (5,6%), all treated with FAC achieved CR. Among them, four had HER-2 3+ (4/25; CR 16%) and three HER2 negative IBC (3/99; CR 3%). Median duration of CR in HER-2+ subset was 15 months (range 7–36+) and in HER-2- 18 months (range 7–101+). Conclusions: Our study shows that incidence of IBC in Serbia is higher than reported in the literature, 8,1% vs 1–4%. Also, it has been shown that very low percentage of IBC patients achieved CR after chemotherapy alone, esspecialy in HER-2- subset of IBC-only 3%, compared to 16% in HER-2+ group, even in the absence of trastuzumab, while the duration of CR in both groups were similar. No significant financial relationships to disclose.
Xanthine oxidoreductase and chemosensitivity in non-small cell lung cancer
Authors: Myint R. , Batus M. , Bonomi P. , Gattuso P. , Warren W. H. , Liptay M. , Faber P. , Basu S. , Xu X. , Kim A. W. 
Published: August 2020

11077 Background: Xanthine oxidoreductase (XOR) is an enzyme involved in the degradation of purines into uric acid and reactive oxygen species and activation of the MAP kinase pathway involved in apoptosis. Decreased XOR expression was shown in recent studies to be associated with more aggressive disease in breast (Linder et al. Clin Cancer Res. 2005;11:4372–4381) and gastric cancers (Linder et al. J Clin Pathol. 2006;59:965–971). The goal of our study was to show that decreased XOR expression was associated with decreased survival in non-small cell lung cancer (NSCLC). Methods: Tissue specimens from 82 patients (pts) were stained using a XOR specific antibody (36 male and 46 female, age range from 40 to 92 years). These included 41 adenocarcinoma, 31 squamous cell, 8 poorly/moderately differentiated, and 2 bronchioloalveolar. XOR staining intensity was measured on a scale of 0 through 4 (0 being no staining). XOR intensity was correlated with clinical characteristics and outcomes using log rank and COX PH regression analysis. Results: Of the 82 pts, 34 received adjuvant chemo, and of these, 15 specimens had low XOR intensity (0–1). These 15 pts received adjuvant chemo and had a median survival of 543 days. In comparison, 19 of the 34 pts receiving adjuvant chemo had specimens with high XOR intensity (2–4). Their median survival was significantly longer at 2,023 days (p=0.007, hazard ratio=0.33). Conclusions: Although we had a small sample size, in our retrospective study, we found that pts who received adjuvant chemo had a longer survival if their tumors expressed high levels of XOR. XOR could be a potential predictor for responsiveness to adjuvant chemo in patients with NSCLC. Pts with decreased XOR may be less responsive to chemo and thus be able to avoid a toxic treatment if it is not significantly beneficial. [Table: see text] No significant financial relationships to disclose.
Expression of metastasis-associated gene products and liver metastases in pancreatic endocrine tumors
Authors: Helm J. , Strosberg J. , Henderson-Jackson E. , Hafez N. , Hakam A. , Nasir N. A. , Coppola D. , Malafa M. P. , Larry K. K. , Nasir A. 
Published: August 2020

11089 Background: Outcomes in well-differentiated pancreatic endocrine tumors can be difficult to predict using pathologic criteria. We recently identified a novel set of 3 metastasis-associated genes by microarray: Palladin, p21, RUNX1T1. Our aim was to evaluate the potential for these markers, individually or in combination, to predict liver metastases as an indicator of adverse outcome. Methods: Palladin, p21, and RUNX1T1 immunostains were done on a tissue microarray of 39 resected primary pancreatic endocrine neoplasms, 14 of which had hepatic metastases. The Allred score was determined as the sum of stain intensity (scored 0–3) and % cells stained (scored 0–5). Receiver operating characteristic (ROC) analysis was used to choose the cutpoint in Allred score (high vs low protein expression) to optimize sensitivity and specificity for predicting liver metastases. Results: Nearly all tumors with liver metastases showed high Palladin and p21 levels (Allred score > 3 and > 4, respectively), while protein expression was lower in the majority of non-metastatic tumors. In contrast, RUNX1T1 expression was low (Allred score < 4) in most tumors with liver metastases, but higher in all except one of the non-metastatic tumors. Individual test sensitivities for predicting liver metastases were 100% for high Palladin, 93% for high p21 and 85% for low RUNX1T1, while corresponding specificities were 63%, 75%, and 96%. Tumors were correctly classified as being metastatic or not (predictive accuracy) by Palladin, p21, or RUNX1T1 expression in 76%, 76%, and 92% of cases, respectively. If abnormal expression of even one of 3 proteins is considered a positive test (parallel testing), then sensitivity of all 3 together for predicting liver metastases was 100%, specificity 48%, and predictive accuracy 68%. Conclusions: 1) High Palladin, high p21, or low RUNX1T1 expression have good sensitivity and specificity for predicting liver metastases in pancreatic endocrine tumors. 2) Parallel testing with all 3 markers achieved 100% sensitivity but at a cost of reduced specificity. 3) Differential expression of these biomarkers may predict aggressive tumor behavior that warrants more aggressive management. No significant financial relationships to disclose.
Dependence of malignant proliferation associated with loss of PTEN on glucose concentration in the hyperglycemic range: Relevance to population studies linking hyperglycemia to unfavorable cancer prognosis
Authors: Pollak M. N. , Blouin M. , Zakikhani M. , Zhao Y. , Algire C. 
Published: August 2020

11113 Background: Loss of function of the tumor suppressor PTEN enhances malignant proliferation, but effects on cellular energy metabolism are less well characterized. Population studies show that the metabolic syndrome (characterized by hyperglycemia, hyperinsulinism, and obesity) is increasingly prevalent in affluent societies and is associated with adverse outcome of many cancers, but the molecular basis for this is poorly understood. Methods: We used a tetracycline-inducible PTEN expression vector in the PTEN-null U251 glioma cell line to characterize effects of PTEN on cellular energy metabolism. Results: Forced expression of PTEN led to decreased phospho-AKTSer473, decreased hexokinase II and HIF-1 alpha levels, and increased p53 levels. While proliferation of PTEN-positive cells was insensitive to variation in glucose concentration at levels higher than 2.5 mM, PTEN-null cells significantly increased proliferation with increasing glucose concentration across normal physiologic range to ∼10 mM. PTEN-null cells consumed more glucose than PTEN-positive cells (17.2 ± 2.0 vs. 8.8 ± 1.5 mM/million cells/48 hrs) and produced more lactate (35.9 ± 4.8 vs. 10.7 ± 2.3 mM/million cells/48 hrs). When cells were incubated in presence of 2-deoxy-glucose (2-DG), growth inhibition was greater for PTEN-null cells (47.4% inhibition relative to control without 2-DG) compared with PTEN-positive cells (10.8% inhibition relative to control without 2-DG). Conclusions: Loss of function of PTEN leads to increased glycolysis, and increased dependence on glucose availability. Only in the presence of glucose in the hyperglycemic range are maximal adverse effects of loss of PTEN on cellular proliferation and survival seen. This provides a novel mechanism to explain at least in part the relationship between hyperglycemia and cancer mortality observed in several large population studies. The data also suggest that PTEN status is relevant to selection of tumors likely to respond to experimental therapies that exploit glucose dependency. No significant financial relationships to disclose.
Effect of trastuzumab on the reduction of hormone receptor expression by neoaduvant chemotherapy in HER2-positive breast cancer
Authors: Hayashi M. , Okumura Y. , Ohsako T. , Arima N. , Nishimura R. 
Published: August 2020

11114 Background: Neoadjuvant chemotherapy (NAC) in primary breast cancer is actively used around the world. Lower ER expression is related to an increased sensitivity of NAC and ER/PgR expression decreases after NAC. Estrogen Receptor (ER) function is coordinated by crosstalk with growth factor signaling, especially that of HER2. Moreover, trastuzumab (T) has an established role in the management of HER-2 positive breast cancer in conjunction with chemotherapy. We examined the effectiveness of NAC and changes in the biological markers, particularly the ER/PgR status after NAC with or without T. Methods: Since April 2002, 143 patients with tumors ≥3 cm in diameter or lymph node metastases have received NAC and surgery. The treatment regimen were as follows; ET in 60 cases, FEC-DOC in 68 cases, and T with anthracycline and taxane in 15 cases. The items investigated were ER/PgR, Ki-67, HER2 and p53. The correlation between the changes in these factors after NAC and the treatment regimen was investigated. Results: The clinical response rate (CR+PR) was 84% in all patients. The pathological CR (pCR) rate was 7.7% in the ET, 20.9% in the FEC-DOC and 33.3% in the T regimen. The Ki67 values and ER/PgR status significantly correlated with pCR. Regarding the changes in biological markers, Ki67 values significantly decreased after NAC in all regimens. In the hormone receptor (HR) positive cases, ER and PgR positive cell rates significantly decreased (ER: 79.8% to 58.3% and PgR: 58.3% to 34.0%). However, in the arm with T, there were no significant changes in ER and PgR positive cell rates (ER: 72.7% to 69.2% and PgR: 50.3% to 38.1%). Conclusions: Lower ER/PgR expression and higher Ki-67 significantly correlated with pCR. Moreover, ER/PgR positive cell rates and Ki67 values significantly decreased after using chemotherapy. However, it appears that the T regimen may restore ER/PgR expression. Thus, ER and HER-2 expression may modify tumor biology via cross-talk even in NAC cases. No significant financial relationships to disclose.
Relationship between single nucleotide polymorphism of estrogen receptor gene and endocrine therapy efficacy in breast cancer
Authors: Yingchun X. , Zhang F. , Wang H. , Ma Y. , Sun L. 
Published: August 2020

1113 Objective: To explore the distribution of single nucleotide polymorphism (SNP) loci of estrogen receptor (ESR1) gene in breast cancer patients and to study the relationship between the SNP genotypes and the efficacy to endocrine therapy. Methods: Fifteen SNP loci ( rs872921 , rs2077647, rs3904766, rs2234693, rs11155816, rs827419 , rs2347867, rs3798759, rs1801132, rs985191 , rs9340931, rs9397463, rs722209 , rs3778099, and rs3798577) of ESR1 gene were selected as genetic markers. PCR-restriction fragment length polymorphisms, PCR-DNA sequencing and allele-specific real time PCR methods were employed to analyze the loci genotype of 240 patients with breast cancer accepted endocrine therapy. Results: The loci rs872921 and rs3904766 were abandoned for poor ploymorphisms, and the other 13 loci had polymorphisms. The frequencies of alleles and genotypes of rs2077647 and rs3798759 were significantly related with the efficacy of endocrine therapy (p < 0. 05). The linkage disequilibrium and the hapotype analysis showed that there were four linkage disequilibrium blocks in ESR1 gene. They were rs2077647∼rs2234693 (LD1), rs2234693∼rs11155816 (LD2), rs9397463∼ rs722209 (LD3), and rs3778099∼rs3798577 (LD4), and the hapotypes of LD2, LD3, s11155816- rs827419 , and rs2347867- rs1801132 were positively related with the efficacy of endocrine therapy (p < 0. 05). Conclusions: Some of the polymorphisms of ESR1 gene and the haplotypes are positively associated with the endocrine therapy efficacy, and maybe account for predicting the endocrine response in breast cancer. No significant financial relationships to disclose.
Drug Response Indicator Test (DRIT) as a predictive test for treatment outcomes in advanced breast cancer patients (ABC)
Authors: Tkaczuk K. H. , Tait N. S. , Ioffe O. , Tan M. , Mohiuddin M. , Chumsri S. , VanEcho D. A. , Sutula M. J. , Lesko S. , Deamond S. , Ts'o P. 
Published: August 2020

1119 Background: There are limited options for selecting an optimal treatment regimen for ABC patients (pts). DRIT is a platform technology that provides a profile of a patient's tumor's sensitivity or resistance to commonly used chemotherapeutic, hormonal, or biological agents as a basis for individualized anticancer treatment approach. DRIT may allow physicians to choose more effective drug treatments before initiation of therapy and improve the efficacy and toxicity profile of cancer therapies. Methods: DRIT analysis is based on fluorescent dye-labeled monoclonal antibody staining followed by computer-assisted microscopy to quantitatively measure expression levels in tumor sections. The interpretation of DRI expression levels results in classification of tumors as sensitive or resistant to treatment with a mechanistically related drug. This study utilized the following drug/DRI combinations: hormonal therapy/estrogen receptor; capecitabine/thymidylate synthase; docetaxel, paclitaxel, abraxane/β-tubulin isoform III; trastuzumab/HER-2; gemcitabine/ribonucleotide reductase. DRIT was performed on the tumor tissue of consented study participants with ABC who were then deemed to be sensitive or resistant to a given agent/agents. We then analyzed retrospectively clinical treatment outcomes (clinically sensitive to therapy defined as-stable disease+partial response+complete response or resistant to therapy-no response to therapy) for 91 treatment interventions in 71 pts with the DRIT tissue data. Results: We found that the DRIT sensitivity was 0.99, with specificity of 0.59, positive predictive value of 0.88, negative predictive value of 0.93 and overall predictive value of 88% for treatment outcomes for this cohort of ABC pts. Conclusions: This study suggests that DRIT can provide more accurate prediction of treatment outcomes for ABC pts than the standard of care approach and therefore has a potential to avoid unnecessary ineffective drug treatment exposure. Prospective study in ABC pts is currently conducted at the UMGCC. [Table: see text]