bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative analysis of angiogenesis between male and female breast cancers
Authors: Bakkar R. , Nahleh Z. , Bui H. , Samaan S. , Sanders J. , Namakydoust A. , Komrokji R. 
Published: March 2020

21101 Background: Tumor angiogenesis and vascularization are essential for the growth and metastasis of tumors. VEGF-C expression and peritumoral lymphocyte density (PLD) are markers of angiogenesis. They have been correlated with poor prognosis in female breast cancer (FBC). The purpose of this study is to characterize VEGF-C expression and PLD in MBC and correlate with FBC specimens. Method: We reviewed records of patients diagnosed with MBC and FBC at the Cincinnati VAMC, from 1989 to 2006. Pathology slides were retrieved. We used VEGF-C (Host Rabbit, PAD: Z-CVC7) . Imunohistochemical stains of VEGF-C were given scores of 0 to 3+ based on nuclear stains. PLD was analyzed based on the number of lymphocyte cells surrounding the tumor; score of 0 to 3+. Slides were reviewed independently by two pathologists. Results: We found nine MBC cases and selected 9 FBC cases. Mean age was 72 in the male patients and 62 in the females. Stages of disease were distributed as follows in MBC versus FBC, 11% versus 22% stage 0, 23% versus 23% stage I, 44% versus 44% stage II, and 22% versus 11% stage IV. Ductal carcinoma was the predominant histology in 88% of FBC and 88% MBC. Other histological types included papillary (1 MBC) and lobular (1 FBC). Among the invasive MBC tumors , 75 % were ER+/PR +, 13% ER+/PR-, and 12% ER -/PR- , compared to 72 % ER+/PR+, 14% ER+/PR-, and 14% ER-/PR- in FBC. Eight out of the 9 MBC cases (89%) stained positive for VEGF-C expression, compared to one FBC case (11%). The 1 male breast intraductal carcinoma was positive for VEGF-C expression, compared to none of the two intraductal FBC. PLD was more intense in male than female tumors : score 0 or 1+: 44% in MBC versus 67% in FBC , score 2+: 22% in MBC Versus 22% in FBC, and score 3+: 22% in MBC versus 11% in FBC. VEGF-C expression did not seem to correlate with ER/PR status. The median survival for patients with MBC was 4.5 years and for patients with FBC 6.9 years. Conclusion: VEGF-C expression and PLD were more pronounced in MBC versus FBC. This finding may correlate with more aggressive behavior of breast tumor cells in male patients, more intense angiogenic reaction and lower median survival. Further studies are warranted to further elucidate the role of angiogenesis in male breast cancer and explore potential antiangiogenic therapeutic modalities. No significant financial relationships to disclose.
Prognostic impact of MKI67 and MMP1 in node-negative invasive ductal and invasive lobular carcinoma of the breast
Authors: Schmidt M. , Boehm D. , von Toerne C. , Lehr H. A. , Hengstler J. G. , Koelbl H. , Gehrmann M. 
Published: March 2020

21102 Background: MKI67 and MMP1 mRNA, which might reflect the biological processes of tumor proliferation and matrix degradation, respectively, have been proposed as prognostic marker in invasive carcinoma of the breast. We compared the expression of both genes in invasive lobular versus invasive ductal carcinoma, which represent the most common histological breast cancer subtypes. Methods: MKI67 and MMP1 mRNA expression was determined by microarray analysis of fresh frozen tumor tissue of 118 patients with invasive ductal and 39 patients with invasive lobular carcinoma. We compared the distribution of these markers between both histological subtypes as well as within each subtype between tumors from patients with or without subsequent distant metastasis or local recurrence by two tailed Mann-Whitney test. Results: MKI67 as marker of proliferation and MMP1 as marker of matrix degradation were significantly elevated in invasive ducal versus lobular carcinomas (p = 0.023 and p < 0.0001, respectively). Furthermore, elevation of both markers were significantly associated with the occurrence of metastasis in ductal (p = 0.023 and p = 0.012) but not in lobular carcinomas (p = 0.986 and p = 0.366). In addition, no significant association was found between these markers and development of local recurrence in patients with ductal (p = 0.304 and p = 0.899) or lobular (p = 0.891 and p= 0.153) carcinomas . Conclusions: Our data suggest that differences exist between ductal and lobular carcinoma of the breast regarding both the expression and the prognostic impact of MKI67 and MMP1. Furthermore, the prognostic relevance of proliferation and matrix degradation was more important for the development of distant metastasis than for the development of local recurrence in ductal carcinoma emphasizing differences in the underlying biology of local recurrence and distant metastasis. No significant financial relationships to disclose.
Residual cancer burden (RCB) is practical and may be more informative than pathological response following neoadjuvant chemotherapy (NC) for locally advanced breast cancer (LABC)
Authors: Sivasubramaniam D. , Komrokji R. , Dhaliwal S. , Sundarajan V. , Nahleh Z. 
Published: March 2020

21103 Background: Complete pathological response (pCR) has been considered a reliable endpoint to assess the benefit of NC. However, different pathological responses ranging from near complete response to resistance would likely indicate different prognostic groups. Method: We studied patients with locally advanced breast cancer (LABC) who received NC between 2001–2006 at the University of Cincinnati. Pathological response to therapy was evaluated. In addition, RCB was quantified according to MD Anderson RCB Calculator index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We examined the correlation between pCR, RCB, event-free survival (EFS) and over all survival (OS) by Cox regression analyses. Result: Pathological slides of 32 patients were analyzed. Median age 52, 38% white and 62% African American. Stage IIB 12% , Stage IIIA 19%, Stage IIIB 53% and Stage IIIC 16% . 72% invasive ducal, 6% invasive lobular and 22% inflammatory cancer. Forty seven percent of tumors were ER +/or PR+ , 53% ER-/PR-, 28% HER-2 /neu + ( IHC 3+ or FISH HER2 gene to chromosome 17 ration > 2.2). Tumor response was as follows: 22% (n=7) achieved pCR , RCB scores ranged between 0- 4.87. By univariate Cox regression analysis, RCB correlated with EFS {Hazard ratio (HR) 1.57 (95% CI 1.04–2.38), p-value 0.018}, and with OS {HR 1.74 (95% CI 0.91 -3.32), p value-0.09}. However, pCR did not seem to correlate with EFS {HR 0 .24 (95%CI 0.03 -1.86–2.38), p-value .172} or OS {HR 0.03 (95% CI 0–89),p value-0.40}. By multivariate Cox regression analysis, RCB was noted to be an independent predictive variable for EFS {HR 1.59 (95% CI 1.04–2.43), p value-0.033} while pCR was not {HR 0.90 (95% CI 0.52–1.57), p value-0.7. Conclusion: RCB was easily quantifiable and appears to be a better predictor of outcome following neoadjuvant chemotherapy in LABC compared to pCR. Higher RCB scores were associated with higher EFS and lower rate of OS. Prospective trials are needed to further evaluate the role of RCB as an endpoint following NC. No significant financial relationships to disclose.
Outcomes after breast cancer in an ethnically diverse cohort of high-risk patients: Differences in survival based on BRCA1/BRCA2 mutation status
Authors: Nanda R. , Huo D. , Cook M. , Chen L. , Hope K. , Cummings S. , Olopade O. I. 
Published: March 2020

21116 Background: Most studies of hereditary breast cancer report that BRCA1 associated tumors are characterized by high grade and hormone receptor negativity, while those associated with BRCA2 are more similar to sporadic cases. Several groups have demonstrated that BRCA1 mutations, but not BRCA2 mutations, are associated with reduced survival in women with breast cancer. These studies have primarily included women of European and Ashkenazi Jewish heritage. No study to date has assessed outcomes in an ethnically diverse cohort of high-risk individuals. Methods: High-risk individuals were identified through the University of Chicago Cancer Risk Clinic (UCCRC). Clinicopathologic data was collected on all patients with breast cancer who had undergone genetic testing and consented to inclusion in research protocols. Recurrence-free survival (RFS) and overall survival (OS) for BRCA1, BRCA2 and non-carriers was compared using the log-rank test. Hazard ratios (HR) and 95% Confidence Intervals (95% CI) were calculated from Cox proportional hazard models. Results: 280 patients from 258 families were studied. 67 were BRCA1 mutation positive, 36 were BRCA2 positive and 177 were non-carriers. 65% of patients were non-Hispanic non-Jewish whites, 15% African American, 15% Ashkanazi Jewish, 3% Hispanic and 2% Asian. At a median follow up of 5 years, 40 patients had relapsed and 22 had died. HRs (95% CI) for RFS of the BRCA1 and BRCA2 carriers relative to non-carriers were 1.6 (0.77–3.33) and 1.3 (0.55–3.09) respectively, when adjusted for year at diagnosis. The adjusted HRs (95% CI) for OS for the BRCA1 and BRCA2 carriers relative to non-carriers were 1.82 (0.48–3.02) and 0.67 (0.15–3.04), respectively. Conclusions: In this study of an ethnically diverse cohort of high-risk individuals, BRCA1 mutation carriers had a poorer outcome as compared to those with BRCA2 mutations or those without identifiable mutations in either gene, although this difference was not statistically significant. This observation is consistent with previous studies of women of predominantly Ashkenzi Jewish and European ancestry. This study was funded by the Falk Medical Research Trust, the Breast Cancer Research Foundation and the Entertainment Industry Fund. No significant financial relationships to disclose.
Gene profiling validation for cancer classification using known primary carcinoma samples
Authors: Lenzi R. , Rashid A. , Ordonez N. , Raber N. M. , Varadhachary G. R. , Floore A. , Stork-Sloots L. , Warmoes M. , Erlander M. , Abbruzzese J. L. 
Published: March 2020

21130 Background: Cancer of Unknown Primary Site (CUP) accounts for 3–5% of all malignant neoplasms. With current diagnostic procedures, approximately 20% of CUP patients have a primary identified. Since formulation of prognosis and treatment selection depends largely on the primary type, diagnostic uncertainty unfavorably affects CUP management. Gene expression profiling has permitted the development of diagnostic classifiers. A clinically usable methodology needs to differentiate a sufficiently large number of primary types. This study focuses on the estimate of the accuracy of gene expression for classification of metastatic tumors in formalin fixed (FF) FNA and core/surgical biopsies. Methods: CupPrint® is a 1900 gene microarray optimized for FF samples which uses a database of 643 cancer profiles to provide a robust method for the discrimination of 51 tumor (sub) types. Metastasis samples of six known primary carcinoma types were studied (lung, pancreas, colorectal, breast, liver, ovary/primary peritoneal carcinoma). To examine the impact of the metastatic site on diagnostic accuracy different biopsy sites were studied, including lung, brain, lymph nodes, liver, peritoneum. Samples were deemed evaluable that contained an estimated >33% tumor cells. mRNA samples from the metastatic lesions were provided in a blinded fashion to the microarray laboratory. Results: For 39 evaluable samples studied so far, the CupPrint® prediction was compared with the pathologic diagnosis. Of the 39, in 34 the primary site of origin was correctly predicted (87% accuracy). In two of the incorrectly predicted samples the site of biopsy (brain and liver respectively) was reported as the primary site. Correlations of molecular profiles to clinical parameters are being explored. Conclusions: CupPrint® appears to be sufficiently accurate to be of potential clinical utility in the diagnosis of CUP. No significant financial relationships to disclose.
Effect of clofarabine on lymphocyte populations in patients treated for solid tumors
Authors: Cunningham C. , Nemunaitis J. , Senzer N. , Richards D. , Vukelja S. , Abichandani R. , Vasconcelles M. 
Published: March 2020

21134 Background: Clofarabine (CLOLAR®) is a next-generation nucleoside analog designed as a hybrid molecule to improve the efficacy and minimize the extramedullary toxicity of other nucleoside analogs. Such analogs are known to have a variety of effects on both humoral and T-cell immune function. Fludarabine, the drug most closely related to clofarabine, causes major alterations in the CD4:CD8 lymphocyte ratios, associated with marked increases in the rate of opportunistic infections. In contrast, gemcitabine has a selective detrimental effect on the B-lymphocyte subset. Therefore, while conducting a phase I dose-finding trial of clofarabine in patients with solid tumors, we investigated its effects on lymphocyte sub-populations. Methods: A phase I dose-finding study is ongoing in patients with solid tumors who receive clofarabine once a week for 3 weeks every 28 days. Blood samples were collected from patients in the highest dose levels before, during, and after clofarabine administration for lymphocyte quantitation and phenotyping using flow cytometry. Results: Of the 11 patients who had samples collected, 5 currently have both baseline and postbaseline values available (1 at the 129 mg/m2 dose level and 4 at the 103 mg/m2 dose level). Overall, the percentage of T cells and CD8 suppressor cells did not decrease significantly with clofarabine administration. In 1 patient where data from 2 cycles were available, CD4 cells decreased slightly after the first cycle, suggesting a possible cumulative effect. However, in all 5 patients CD19 cells decreased significantly after the first infusion of clofarabine and remained suppressed for the duration of the study period. Conclusions: Although clofarabine is a purine analog (as is fludarabine), its effects on lymphocyte subsets more closely resemble gemcitabine, a pyrimidine analog. If substantiated, these findings should have bearing on future decisions about appropriate drug combinations involving clofarabine. No significant financial relationships to disclose.
Zoledronate acid modifies the lipid transporters profile in human prostate cancer cell lines
Authors: Toledo Lobo M. , Arenas Jiménez M. , Huertas Martínez L. , Sacristán lópez S. , Moyano Jato A. , Fernández Fernández E. , Martín Hidalgo M. , Martín del Río R. , Gómez Pinillos A. 
Published: March 2020

21135 Background: The mechanism through wich zoledronic acid exerts its activity is poorly understood. Low density lipoprotein receptor (LDLR) and scavenger receptor class B type 1 (SRBI) overproduction is an important mechanism in cancer cells for obtaining more essential fatty acids and cell growth. The effects of in vitro zoledronate treatment on the lipid metabolism of prostate cancer cell lines were studied. Methods: Three prostatic cancer cell lines, androgen insensitive PC3, androgen dependent low-passage (LP) LNCaP and androgen independent high-passage (HP) LNCaP cells were studied. Cells were plated either in RPMI with 5% foetal calf serum and lipoprotein depleted serum (LPDS) and were treated with zoledronate at different concentrations. The lipid transporters profile was analyzed by western blotting for LDLR and SRB1. Results: The same LDLR bands profile was observed in all cell lines, 160 and 105 kDa. The basal levels of LDLR were higher in the PC3 cells. Zoledronate therapy induced LDLR expression in all cell lines but PC3 were less sensitive to this effect. Cells cultured with LPDS showed an enhanced expression of LDLR and PC3 cells were less sensitive to this effect. HP LNCaP cells were the most affected by lipoprotein deprivation however this effect diminished 72 hours after treatment. The bands profile for SRBI consisted of a 65 kDa predominant band and a 40 kDa band in both LP/HP LNCaP cells. In PC3 cells main band was located in 65 kDa and accessory band in 30kDa. The basal levels of the 65kDa band were higher in HP than in LP LNCaP or PC3 cells and zoledronate therapy caused a dose- dependent induction in HP LNCaP and dose-dependent reduction in PC3 cells, LP LNCaP cells were resistant to the treatment. LPDS induced SRBI levels in all cell lines inverting the effect caused by zoledronate in HP LNCaP cells in complete culture medium and at high doses (100μM) a complete inhibition of SRBI protein was found. Low molecular weight bands changed in the same way as the 65 kDa band. Conclusions: LDL-R and SRBI have been isolated in prostate cancer cell lines. Based on previous cell growth studies, the lipid transporters profile might be significantly involved in the resistance to zoledronate therapy. Lipoprotein regulation pathways should be considered in the therapy of metastatic prostate cancer. No significant financial relationships to disclose.
Association of interleukin-1 gene polymorphisms with gastric cancer: A meta-analysis
Authors: Vincenzi B. , Santini D. , Patti G. , Pantano F. , Venditti O. , Rocci L. , Frezza A. , Coppola R. , Graziano F. , Tonini G. 
Published: March 2020

21142 Introduction: Previous studies on the association between interleukin-1 (IL-1) genetic polymorphisms and the risk of gastric cancer have produced conflicting results. The purpose of this study was to examine the association between IL-1 genotype and gastric cancer by systematically reviewing the original studies. Materials and Methods: We searched the MEDLINE, CENTRAL, and PubMed databases (last research performed on July 2005) and reviewed cited references to identify relevant studies. Search key words were: gastric cancer (OR stomach cancer OR gastric adenocarcinoma OR stomach adenocarcinoma) and IL-1 (OR IL1). The literature review identified 23 titles that met the search criteria. Data from 15 articles that investigated the association between any of IL-1B-511 and IL-1B-31 polymorphisms and gastric cancer met the inclusion criteria, and they were included in the meta-analysis. Eight studies evaluated the role of IL-1B-511, four the role of IL- 1B-31 and three investigated both IL-1B-511 and IL-1B-31. Results: By pooling all the studies identified, our study shows that individuals IL-1B-31T carrier have got an increased risk developing gastric cancer (OR of 1.25; 95% CI 1.06–1.47) in particular in Caucasian sub-group (OR of 1.41; 95% CI 0.97–2.05). IL-1B-31CC genotype confers a decreased risk (OR of 0.80; 95% CI 0.68–0.95) especially in Caucasian population (OR of 0.71; 95% CI 0.49–1.03) compared to Asians (OR of 0.83; 95% CI 0.69–0.99). This association might be explained with the well-known near complete linkage disequilibrium between IL1B-511T and IL1B-31C polymorphism. Furthermore our results suggest a strong association between IL1B-511T polymorphism and gastric cancer risk only in Caucasians and not in Asians. Conclusions: In conclusion, although affected by the common bias of each epidemiologic studies, this pooled analysis suggests that IL1B-511T polymorphism is associated with an increased risk of developing gastric cancer in Caucasian population. No significant financial relationships to disclose.
Trastuzumab-HER/2 binding induced inhibition of cell growth and HER/2 tyrosine kinase activity
Authors: Welt S. , Shay T. , Lanning C. , Horton K. , Kostyal D. 
Published: March 2020

21146 Background: Cell lines containing the HER/2 amplicon are sensitive to Trastuzumab (T) mediated inhibition of cell growth. T blockade of cell growth signaling pathways have been hypothesized to occur by two mechanisms, inhibition of homo and hetro-dimerization of HER/2 with members of the EGFr family and inhibition of HER/2 phosphorylation. Methods: BT 474 and SK-BR3 breast cancer cell lines containing the HER/2 amplicon were cultured under condition demonstrating inhibitory effects of T by MTT and 3H-Thymidine incorporation (0.25–50 micrograms/ml for up to 9 days). RNA extracts from treated and un-treated cells were analyzed and compared using two immunoassays for phosphorylated HER/2. Various growth conditions were assessed for T inhibition of phosphorylation including, serum free media, fetal calf serum, human pre and post menopausal serum, breast cancer patient's serum and normal male serum. Results: Breast cancer cell lines BT 474 and SK-BR3 both demonstrated cell growth inhibition when cultured with T over a wide range of concentrations down to 0.25 microgram/ml. The inhibitory effects on SK-BR3 were low but statistically significant in both MTT and 3H-Thymidine incorporation assays. Examining this same concentration range of T on these cell lines demonstrated no appreciable reduction of phosphorylation by western blot analysis at various time points after exposure to T. Two different immune assays for HER/2 phosphorylation were analyzed. Further examination of replacement of fetal calf serum by human female pre and post menopausal serum samples or similar samples from breast cancer patients did not result in reduction of the phosphorylation signal. Conclusions: In this in vitro model T does not mediate effects through HER/2 tyrosine kinase inhibition under conditions that simulate clinical conditions. Whether inhibition of phosphorylation will be apparent at later time points is unknown. These finding may explain the activity of lapatinib, a HER/2 tyrosine kinase inhibitor, on T resistant breast cancer. No significant financial relationships to disclose.
Preoperative concurrent chemo- and endocrine therapies for women with large operable breast cancer expressing steroid hormone receptors
Authors: Dellapasqua S. , Balduzzi A. , Torrisi R. , Ghisini R. , Peruzzotti G. , Rocca A. , Cardillo A. , Goldhirsch A. , Colleoni M. 
Published: March 2020

21153 Background: Preoperative chemotherapy and endocrine therapy yielded low pathological complete remission (pCR) rates in patients with endocrine responsive breast cancer. Methods: Patients with large operable endocrine responsive (ER ≥ 10% of the cells) breast cancer (cT2-T3, N0–2, M0) were treated in 2 consecutive studies with preoperative chemotherapy (Study I: 6 courses of either fluorouracil, leucovorin, vinorelbine (FLN), or vinorelbine, cisplatin, and continuous infusion of fluorouracil (ViFuP), chosen at the discretion of the treating physician; Study II: an oral regimen with capecitabine and vinorelbine (CAVINO). In both studies concurrent endocrine therapies (letrozole, either alone or if premenopause, with triptorelin) were given. Results: Sixty-five (58 evaluable) and fifty-five (all evaluable) patients were enrolled to Studies I and II, (ER >50%, 51 and 50; Ki 67 = 20%, 42 and 39; cT2/3: 36 / 22 and 35 / 20; premenopausal 40 and 38) respectively. In Study I there were 43 objective responders (74%, 95% CI 63–85%), 4 of whom had pCR. In Study II 34 patients (62%, 95% CI 49–75%) had an objective response. Breast conserving surgery became possible for 64% and 62% of the patients in Study I and II, respectively. Conclusions: Intravenous, non anthracycline containing regimens together with tailored menopause status-adapted endocrine therapy, warrants further investigations in the preoperative setting. No significant financial relationships to disclose.