bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical relevance of small tumor size (pT1a-b) for patients with HER2-positive, node-negative breast cancer
Authors: Curigliano G. , Fumagalli L. , Bagnardi V. , Rotmensz N. , Locatelli M. , Ghisini R. , Viale G. , Veronesi P. , Goldhirsch A. 
Published: August 2020

e22011 Background: Prognosis of patients with node-negative, HER2-positive disease and tumor size ≤ 1 cm is a matter of controversy. We assessed the prognostic role of HER2 overexpression/amplification in a large series of patients with node-negative, pT1a,b breast cancers. Methods: All consecutive patients with pT1a,b pN0 M0 HER2-positive breast cancer who underwent surgery at the European Institute of Oncology (IEO) from 1995 to 2006 were identified. No patient received trastuzumab in the adjuvant setting. A matched cohort comparison was done using as variables hormone receptor status (positive vs. negative), age at surgery and year of surgery. Comparison group included patients with HER2-negative breast cancer matched 1:1 for hormone receptor negative group and 1:2 for hormone receptor positive group. We estimated rates of local recurrence, distant metastases, disease free survival (DFS) and overall survival (OS) in the hormone receptor positive and hormone receptor negative group. Results: We identified 150 patients with pT1a,b pN0 M0 HER2-positive tumors. The median follow-up was 4.6 years (range 1.0–9.0). In the hormone receptor positive group 5-year DFS was 99% [95% CI: 98%-100%] for HER2-negative and 92% [95% CI: 86%-99%] for HER2-positive disease. In the hormone receptor negative group 5-year DFS was 92% [95% CI: 84%-100%] for HER2-negative and 91% [95% CI: 84%-99%] in HER2-positive disease. Overall, for patients with hormone receptors positive and negative disease, the hazard ratio (HR) associated to HER2 overexpression was 2.4 (95% CI: 0.9–6.5, p=0.09). OS in HER2-positive pT1a,b pN0 M0 breast cancer was similar in hormone receptor positive and negative patients (p=0.93). Conclusions: Node-negative, HER2-positive, pT1a,b breast cancer have a low risk of locoregional and distant recurrence within the first 5 years after diagnosis. In patients with hormone receptor positive, pT1a,b N0 M0 tumors, HER2 overexpression seems to be associated with a dire prognosis (HR=5.2, 95% CI: 1.0–25.9) in terms of DFS. No significant financial relationships to disclose.
Clinical implication of ERCC1 overexpression in advanced biliary tract adenocarcinoma patients treated with platinum-based palliative chemotherapy
Authors: Hwang I. , Chi K. , Do J. , Lee G. , Kang J. , Oh S. , Kwon H. , Park H. , Lee S. , Lee S. , Jang J. 
Published: August 2020

e22018 Background: Several clinical studies have shown that Excision repair cross-complementation group1 (ERCC1) overexpression is associated with resistance to platinum-based chemotherapy and poor prognoses in several tumors. However these studies have never been tried for biliary tract cancer. The aim of this study was to evaluate the association between ERCC1 expression and treatment outcomes in advanced biliary tract adenocarcinoma patients treated with platinum-based palliative chemotherapy. Methods: We analyzed 45 patients with histologically confirmed adenocarcinoma of biliary tract at 5 institutions between January 2002 and March 2008. ERCC1 expression was assessed by immunohistochemistry from biopsy specimens. Results: ERCC1 expression was positive in 17 of 45 specimens (37.8%). 26 (57.8%) of 45 patients showed clinical benefits(including complete response, partial response and stable disease). Among 26 patients who obtained clinical benefits, seven (27%) were positive for ERCC1 expression and ninety (73%) were negative (p=0.079). With a median follow-up of 6.6 months (range, 0.9–39.4 months), median Progression free survival (PFS) and Overall survival (OS) were 4.4 months (95% CI, 3.2–5.6 months) and 8.5 months (95% CI, 6.1–10.9 months), respectively, for the total study population. On univariate analysis, PFS was 2.3 months for patients with ERCC1 positive tumor and 5.3 months for those with ERCC1 negative tumor (P = 0.053). However OS was significantly longer in the ERCC1-negative group than in the ERCC1-positive group (10.0 vs 4.4 months, respectively; P = 0.001). Other factors affecting the prolongation of OS were objective response rate (P = 0.016) and clinical benefits (P = 0.001). A Cox proportional hazard model showed that negative ERCC1 expression (hazard ratio 0.405, 95% CI, 0.200–0.820; P = 0.012) and clinical benefit (hazard ratio 0.183, 95% CI 0.080–0.420; P = 0.001) were significant independent prognostic factors for the prolongation of survival. Conclusions: These results suggest that advanced biliary tract adenocarcinoma patients with ERCC1-negative tumors show a survival benefit from palliative chemotherapy with a platinum- containing regimen. No significant financial relationships to disclose.
Proteomics: A panel of seven serum biomarkers as a promising diagnostic tool for breast cancer
Authors: Lastra R. , Monasterio A. , Alvarez-Busto I. , Mayordomo J. , Algorta J. , de Juan A. , Pericás I. , Garijo F. , Aberro J. , Fernandez S. , Martín M. 
Published: August 2020

e22019 Background: Conventionals serum biomarkets have a low sensibility in breast cancer diagnosis. Proteomic is a promising tool to identify new proteins profiles to be used in screening and early diagnosed. Methods: 1)Biomarker identification: Serum proteins from 114 women were separated and analysed by bidimensional gel electrophoresis; data from 72 patients (p) were compared with those from 42 control women to search for differentially expressed proteins. Several comparisons were performed between controls and p regarding clinical parameters such as histological type, tumour stage and lymph node affection (-/+). A total of 53 spots were found to be differentially expressed and identified by mass spectrometry (MS) as potential breast cancer biomarkers.2) Protein Chip development: A Protein Chip was developed with antibodies against six biomarkers and three control proteins (an antibody for the detection of a spiked control, for data normalization and two proteins as positive and negative controls). An antibody against CA15–3 antigen was also included as a reference breast tumour marker to be compared with our biomarker panel. 3) Clinical validation of the Protein Chip: A clinical validation study was carried out with 75 healthy women and 125 breast cancer p. After multivariate statistical analysis of the biomarker data, CA15–3 was discarded due to its low significance while a panel of 5 biomarkers was obtained as the best predictive model to discriminate p from healthy subjects. Results: 53 diferentially expressed proteins have been identified as potential breast cancer serum biomarkers after analysing 114 serum samples by 2DE Technology. A Protein Chip has been developed for the simultaneous detection of five serum biomarkers and three control proteins. After clinical validation with 200 p and healthy women, the sensitivity of the Protein Chip to detect breast cancer was 95% and its specificity was 27%. Conclusions: The high sensitivity of the Protein Chip suggests that it could be a valid tool to complement mammography (sensitivity < 80%) in breast cancer screening programs, specially when its sensitivity tends to decrease, as it happens in young women and dense breast cases. Larger clinical validation trials are being developed. This work is supported by INDAS BIOTECH. No significant financial relationships to disclose.
Targeting prostate cancer progenitor cells with telomerase interference: A novel therapeutic strategy
Authors: Goldkorn A. , Xu T. 
Published: August 2020

e22029 Background: We investigated whether telomerase, which is critical for benign stem cell activation, also plays a role in prostate cancer progenitor cells (PCPCs), which are thought to mediate therapy resistance and cancer progression, and we tested whether telomerase interference can effectively inhibit PCPC proliferation. Methods: A putative PCPC population was isolated from human prostatectomy specimens via collagen attachment and FACS selection for integrin α2β1 and CD44. PCPCs were characterized for gene expression (RT-PCR), clonogenicity (colony formation), invasiveness (matrigel chamber), and telomerase activity (qPCR-TRAP). PCPC telomerase interference was accomplished by lentiviral expression of 2 constructs: telomerase RNA with an altered template region (MT-Ter) and siRNA targeting wild-type telomerase RNA (anti-Ter siRNA). The effects of these constructs were assessed by measuring PCPC viability (MTS) and apoptosis (TUNEL assay). Results: An integrin α2β1+CD44+ putative PCPC population was isolated from 6 human prostate tumors. This population expressed high levels of “progenitor phenotype” genes (ABCG2, β-catenin, NANOG, Oct3/4) and low levels of “differentiated phenotype” genes (AR and PSA). PCPCs yielded >50 colonies per 1000 cells seeded on collagen after 3 weeks vs. none from FACS- cells, and matrigel chamber assay showed 10% of the PCPC population invading over 24 hours vs. none of the FACS- population. Most importantly, PCPCs possessed at least 20- fold greater telomerase activity than FACS- cells, and induction of telomerase interference in PCPCs via MT-hTer and anti- hTer siRNA expression elicited a brisk apoptotic response (TUNEL) by day 3 in >90% of cells, with concomitant near-complete growth inhibition (MTS). Conclusions: We have shown that human prostate tumors contain a subpopulation of prostate cancer progenitor cells (PCPCs) marked by an undifferentiated gene expression profile, vigorous clonogenicity and invasiveness, and high levels of telomerase activity that can be successfully exploited to neutralize these cells. Ongoing studies are investigating the in vivo effects of telomerase interference on PCPC tumorigenicity in mouse models. No significant financial relationships to disclose.
Heterogeneous expression of prognostic and predictive antigens in primary and metastatic gastric cancer
Authors: Joka M. , Pietsch K. , Paulick S. , Issels R. , Jauch K. , Mayer B. 
Published: August 2020

e22030 Background: Metastatic spread of cancer cells is a key event in tumor progression and in determining the prognosis of patients with malignant disease. This study evaluated the expression of prognostic and predictive molecules in primary and metastatic gastric cancer. Our objectives were to correlate the expression pattern with the clinicopathological features and patient survival and confirm the results using a coculture spheroid model. Methods: The clinicopathological features of 94 patients (57,4% male, 42,6% female, median age of 66,2 years) with gastric cancer were characterized using multivariate and univariate analysis. Further we compared the expression profile of biomarkers, namely EPCAM, CD44s, HLA-ABC and the associated β chain, HLA-DR, ICAM-1, LFA-3 and E-Cadherin in primary gastric tumors (n=94) and their synchronous metastases (regional lymph nodes n=32, liver n=14, peritoneum n=17) using immunoperoxidase staining. A coculture in vitro model, i.e. the homo- and heterotypic spheroid model were performed as a functional test system to confirm the microenvironmental impact on the biomarker expression level. Results: Strong HLA-ABC expression was found in both primary and metastatic tumors. High expression of HLA-ABC in liver metastases significantly correlated with metastatic disease (UICC TNM stage IV, p=0,026). Contrary, the detection of HLA-DR on the cancer cells correlated with the degree of the inflammatory infiltrate (CD45, p=0,019). With respect to CD44s, the prognostic marker was upregulated in the metastatic tumors independently of their localisation (p=0.009) compared to the primary lesions. E-cadherin and LFA-3 expression were preferentially increased in distant metastases, but not in locally advanced gastric tumors (liver: E-cadherin, p=0.001; liver and peritoneum: LFA-3, p=0.0067). E-cadherin expression was upregulated in the heterotypic spheroid model coculturing primary liver cells and N87 gastric cancer cells (80% E-cadherin positive N87 cells) compared to the homotypic spheroid model consisting of N87 cells alone (40% E-cadherin positive N87 cells). Conclusions: These data suggest the consideration of the metastatic protein profile for the selection of cancer patients in new molecular therapeutic strategies. No significant financial relationships to disclose.
Correlation of plasma TIMP-1 levels and disease-free survival in primary colorectal cancer independent of serum CEA levels
Authors: Nielsen H. J. , Brünner N. , Christensen I. J. 
Published: August 2020

e22040 Background: Introduction of independent prognostic markers may play a significant role in future treatment of early stage colorectal cancer (CRC). CEA is still the only recommended (ASCO and EGTM) serological marker in CRC. However, Tissue Inhibitor of Metallo Proteinases-1 (TIMP-1), which is a glycoprotein that acts as an inhibitor of most of the active matrix metalloproteinases, has previously been shown to carry independent prognostic information in patients with primary CRC. The purpose of the present study was to assess the combination of preoperative serum CEA and plasma TIMP-1as prognostic markers in patients undergoing resection for primary CRC. Methods: In the present prospective study serum and plasma samples were collected before surgery from 422 patients with primary CRC stage I-III. CEA was determined in serum by a commercial assay and TIMP-1 was determined in plasma using a thoroughly validated, in-house ELISA. Time to recurrence or death of CRC was registered and the association to serum CEA and plasma TIMP-1 levels were studied in a Cox multivariate model including age, gender, disease stage and tumor location. Hazard ratios and 95% confidence intervals (HR (95%CI)) for disease free survival (DFS) were calculated. Results: An event was recorded in 186 patients, 75 had local recurrence, 103 had a distant metastases (28 of these patients had both local recurrence and distant metastases) and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale (base 2), both serum CEA and plasma TIMP-1 were statistically significant in a multivariable analysis with HR=1.12 (1.03–1.21) and HR=1.51 (1.12–2.04), respectively. Additional calculations of low CEA plus low TIMP-1, high CEA plus low TIMP-1, low CEA plus high TIMP-1 and high CEA plus high TIMP-1 showed that high plasma TIMP-1 levels carried prominent information of poor prognosis independent of CEA. Conclusions: Preoperative serum CEA and plasma TIMP-1 levels were independent predictors of disease free survival for patients with primary CRC. Combination of the two proteins showed that TIMP-1 was a prominent predictor of poor DFS independent of CEA. [Table: see text]
Expression of CD24 as a predictor of prognosis of hepatocellular carcinoma after operation
Authors: Fan J. , Yang X. , Xu Y. , Shi Y. , Zhou J. , Qiu S. 
Published: August 2020

e22043 Background: CD24 expression has previously been reported in hepatocellular carcinoma (HCC), although little is known about its prognostic significance. The aim of this study is to evaluate the relation of CD24 expression and its prognostic significance in HCC. Methods: CD24 expression in stepwise metastatic HCC cell lines and tumor tissues from 50 HCC patients was investigated by quantitative real-time reverse transcription-PCR and Western blot analyses. The role of CD24 was investigated by depletion CD24 expression in HCC cells through small-interfering RNA. Tumor tissue microarrays of 314 HCC patients who underwent resection between 1997 and 2000 were used to detect the expressions of CD24, β-catenin and PCNA expression. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Results: CD24 was overexpressed in the high metastatic HCC cell line and in tumor tissues of recurrent patients. Depletion of CD24 caused a notable decrease in cell proliferation, migration and invasiveness in vitro. CD24 was confirmed as an independent predictor for overall survival (p<0.001) and relapse-free survival (p<0.001), regardless of recurrence time, AFP level, TNM stage and Edmondson stage. High expression of CD24 in HCC tissues was significantly associated cytoplasmic/nuclear accumulation of β-catenin (p=0.023), high tumor proliferate status (p=0.018) and diffused intrahepatic recurrence and distance metastasis (p=0.026). Adjuvant TACE after operation reduced the early recurrence (≤1 year) in CD24+ HCC patients (p=0.024), while there had no significant changes in CD24- patients (p=0.284). Conclusions: High expression levels of CD24 were related with high invasive and metastatic potential, high tumor proliferation status and activation of Wnt/β-catenin pathway. The expression of CD24 provides new prognostic information about HCC prognosis and targeted therapy to CD24+fraction in HCC may comprise a promising anti-recurrence strategy for HCC patients after surgery. No significant financial relationships to disclose.
Comparative genomic and protein signatures and intratumoral treatment responses in patients with metastatic breast cancer (MBC) treated with paclitaxel (PTX) and 2-methoxyestradiol (2ME2)
Authors: Herold C. I. , Yang I. , Chi J. , Sidor C. , Parrillo L. , Liotcheva V. , Welch R. A. , Arnott J. , Dewhirst M. W. , Blackwell K. L. 
Published: August 2020

e22049 Background: Tumors respond to both chemotherapy and radiation through a number of poorly understood survival mechanisms. These potential mechanisms include upregulation of anti-apoptotic and pro-angiogenic pathways, including those regulated by HIF-1α. Sequential MBC biopsies were used to examine 1) the effects of PTX on intratumoral HIF-1α mediated pathways; and 2) the ability of a HIF-1α inhibitor (2ME2) to modulate the tumor's HIF- 1α response to PTX. Methods: Key eligibility included pts with MBC, ECOG 0–2, unlimited prior therapies, and biopsiable tumors. Pts were treated on a 28-day schedule with weekly PTX (90 mg/m2 D1, D8, D15) and daily oral 2ME2 (1000, 1250,1500 or 2000 mg qid starting D8) and had 3 tumor biopsies: baseline (A); D8 post-PTX/pre-2ME2 (B); D22 post-PTX/post- 2ME2 (C). Serial biopsies were compared for genomic and single protein changes. Results: 20 pts (median age 52 yrs [31- 75]) were treated. 60% had ≥2 prior regimens for MBC, 35% had ≥3. No unexpected grade 3/4 toxicities were seen: neutropenia (n=6), anemia (2), hypophosphatemia (2), PE (1). The clinical benefit rate was 25% (4 PR, 1 SD). There were 13 pairs of tumor biopsies to compare points A/B and 10 to compare B/C. There were no consistent gene expression changes between A and B. Significant differences at C vs. B included changes in hypoxia-responsive genes (including CA9, HIF-2α) and upregulation of pro- angiogenic factors and hemoglobin transcripts. For the B/C comparison, 2 distinct groups emerged: the first (biopsy site liver) showed downregulation of gene expression programs driven by ER and the second (lymph node, breast) showed upregulation of endothelial cell- related genes. Conclusions: Combination therapy with PTX and 2ME2 is a well-tolerated and viable option for delaying disease progression for patients with heavily pretreated MBC. Significant gene expression changes before and after exposure to 2ME2 may reflect changes in tumor microcirculation consistent with the idea of vascular normalization. The potential significance of the differences in gene expression observed in the 2 distinct groups remains to be investigated. Supported by Komen Grant BCTR0504044 (MWD). [Table: see text]
The association of cancer and allergic symptoms among female adult participants aged ≥40 years in NHANES III
Authors: Chae Y. , Kim J. , Tester W. 
Published: August 2020

e22060 Background: The contribution of inflammation to carcinogenesis has been reported. Allergic diseases are now recognized as a systemic inflammatory process. We investigated whether common allergic symptoms are associated with cancer risk. Methods: The Third National Health and Nutrition Examination Survey (NHANES III) is a stratified probability sample of the U.S. population collected during 1988–1994. The prevalence of cancer excluding skin cancer was obtained by personal medical interview. Allergic symptoms were categorized into three categories: no symptoms (NO), rhinitis/conjunctivitis without wheezing (RC), and wheezing (WZ). Other risk factors for cancer were defined by NHANES III questionnaire and results of physical examination. Multivariate logistic regression was used to obtain odds ratios of cancer according to the existence of allergic symptoms adjusted for other possible confounding variables considering complicated sampling methods and weights. Results: 4,558 female adults were selected out of 5076 female adults aged ≥40 years who participated in both interview and physical examination. Cancer was present in 7.41% (n=301). 36.3% (n=1,893) of subjects did not have any allergic symptoms (NO), 47.6% (n=1,979) showed RC, and 16.2% (n=726), WZ. The prevalence of cancer was 5.43% in NO, 7.63% in RC, and 11.23 in WZ (p=0.006). Unadjusted odds ratios of cancer were 1.44 (95% CI: 0.99–2.08, p=0.053) in RC and 2.20 (1.27–3.80, p=0.006) in WZ compared with NO. Odds ratios are 1.49 (1.00–2.22, p=0.048) in RC and 2.08 (1.11–3.89) in WZ adjusting for age, race, education, income, asthma, COPD, C-reactive protein, obesity, smoking, alcohol drinking, physical inactivity, and menopausal status. In subgroup analysis, adjusted odds ratios of breast cancer were 1.89 (1.04–3.42, p=0.037) in RC and 2.08 (0.90–4.78, p=0.084) in WZ, while other cancers showed no statistically significant associations. Conclusions: Common allergic symptoms, even symptoms of allergic rhinitis of conjunctivitis, may be associated with increased risk of cancer in female adults. It supports the hypothesis that systemic inflammation mediators may trigger or promote cancer development in all parts of the body. However, prospective studies are required to validate our findings. No significant financial relationships to disclose.