bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participant characteristics on an international NCIC CTG breast cancer prevention trial
Authors: Richardson H. , Johnston D. , Goss P. E. 
Published: March 2020

1531 Background: Antagonizing estrogen with tamoxifen has set the precedent for preventing breast cancer. Aromatase inhibitors reduce contralateral breast cancer in the adjuvant setting more than tamoxifen. The goal of MAP.3 is to determine whether exemestane reduces invasive breast cancers in post-menopausal women at risk for the disease. Methods: NCIC CTG MAP.3 is a randomized placebo controlled double blind trial of exemestane versus placebo. Recruitment began in September 2004 in North America and Spain. Criteria for entry on MAP.3 include: a Gail score of 1.66%; previous benign breast disease including LCIS; age over 60. The target sample size for the trial is 4560. Baseline characteristics of women enrolled thus far on MAP.3 were reviewed to determine whether their projected risk of breast cancer is consistent with the assumptions made in designing the trial. Results: Baseline characteristics are available on the 1784 women enrolled to MAP.3 to date. Over 70% of participants are over 60 years old (mean 64; SD=8.2 years) and the majority of the women are Caucasian (85%). The average 5-year risk of breast cancer is 2.7% (median, 2.2%). However, a greater proportion of women over 60 (30%) have a substantially lower Gail score (<1.66) compared to women less than 60 years of age (8%). Few women in the MAP.3 cohort have been enrolled on a basis of a history of prior breast atypical hyperplasia or LCIS (8%), or DCIS treated with mastectomy (2%). Nearly half the MAP.3 participants (45%) have at least one first degree relative with malignant breast cancer, and 7.5% of these women have 2 or more first degree relatives with the disease. Conclusions: The risk profile of the women on MAP.3 will determine the event rate and therefore the time to trial unblinding and analysis. This initial description of the MAP.3 population enrolled thus far indicates a slightly lower baseline breast cancer risk in comparison to the risk profile of those enrolled in previous breast cancer prevention trials with tamoxifen or raloxifene (NSABP P1, IBIS-1 and STAR). Reasons for this difference are being explored. [Table: see text]
Content and method of parental disclosure of genetic risk to young adult and minor children in BRCA families
Authors: Pawlowski K. , Patrick-Miller L. , Daugherty C. K. , Olopade O. I. , Dignam J. J. , Ibe C. N. , Hlubocky F. J. , Cummings S. A. , White M. A. , Dudlicek L. , Bradbury A. R. 
Published: March 2020

1536 Background: Prior research has found that many BRCA mutation carriers report discussing their genetic test results with their minor children. The content, method and process of this communication have not been previously described. Methods: 20 parents (yielding 42 parent-offspring pairs, POP) have completed a 62-item questionnaire regarding the content and methods of communication of genetic risk to offspring. Results: Of 19 (45%) POP where parents reported disclosure of their BRCA mutation to offspring in response to a binary (yes/no) question, all reported telling their children about the genetic mutation itself, as well as the parents’ risk for cancer. In 74% of POP the offspring’s chance of inheriting the mutation or risk for cancer were said to have been communicated. In 53% of POP parents reported discussion of parental risk reduction measures, and in only 37% of POP parents reported communication of offspring risk reduction measures. Of the POP where parents reported some communication of cancer risk, 22% described incorporating written materials. In 75% of POP parents reported communication through multiple conversations over time (1 -20 conversations, up to 4 years). Conclusions: Although many BRCA carriers report discussing their genetic mutation with offspring, the content and extent of parental communication is variable, often including information regarding the genetic mutation, but less frequently the offspring’s risk of inheriting the gene and infrequently communication regarding risk reduction measures. Further research on this expanding cohort will allow for analyses of parent and child factors associated with disclosure content in order to guide the development of interventions to facilitate age and content-appropriate communication of genetic risk to at-risk offspring. No significant financial relationships to disclose.
The effects of licofelone, a dual lipoxygenase and cyclooxygenase inhibitor, with and without rosiglitazone in human MCF-7 and MDA-MB-231 breast cancer cells
Authors: Kurkjian C. , Janakiram N. B. , Guruswamy S. , Rao C. V. , Ozer H. 
Published: March 2020

1537 Background: Clinical and preclinical studies suggest that cyclooxygenase (COX)-2 inhibitors reduce the risk of various cancers, however, their administration is associated with an increased cardiovascular risk. Agents with 5-LOX/COX inhibition provide a possible approach for improving chemopreventive efficacy without unwanted side effects. COX and LOX inhibition have also been associated with an increase in PPAR γ expression. The present experiments tested the effects of licofelone (L) in breast cancer cell lines and assessed whether dual inhibition of LOX and COX may potentiate the action of rosiglitazone (R). Methods: MDA-MB-231 and MCF-7 cells were exposed to sub-toxic concentrations of L and R alone and in combination and analyzed for growth inhibition (MTT method), apoptosis (EB-AO and DAPI methods), cell-cycle analysis (flow cytometry), and protein expression (immunoblot method). Results: L and R inhibited cell growth in a dose-dependent manner in both cell lines. Combination therapy resulted in significant rates of apoptosis, particularly at high doses in both cell lines (p<0.001). Flow cytometric analysis showed that L and R exhibited cell cycle arrest at the G0/G1 phase in MDA-MB-231 cells. The low dose combination did not promote cell cycle arrest while the higher dose combination therapy demonstrated significant inhibition (p <0.0009). In MCF-7 cells, G0/G1 phase blockade was noted in L and R treated cells as well as in the low dose simultaneous combination therapy. Intermediate and high dose combination therapy exhibited increased cell cycle arrest at G0/G1 when L was administered 12 hours before R (p = 0.0030 and 0.0017). Western blot analysis showed increased expression of p21WAFI/CIPI and decreased cyclin D1 expression in both cell lines after therapy. Both agents induced caspase-3 expression in MDA-MB-231 cells at high concentrations, with even higher expression observed in the combination treatment. MCF-7 cells demonstrated PARP cleavage at all doses when compared to control. Conclusions: Our results suggest that L is a potential agent for prevention and treatment of breast cancer and the combination of low doses of L and R provide further promise in improving efficacy against breast cancer. No significant financial relationships to disclose.
Prevention of MEK1-associated tumours in murine epidermis by inhibition of interleukin-1
Authors: Lal R. , Watt F. M. 
Published: March 2020

1541 Background: Pro-inflammatory cytokines have a role in facilitating a pro-tumourigenic microenvironment in chronic inflammatory diseases and may identify targets for chemoprevention. The host microenvironment has a role in driving the malignant capacity of tumours, determining whether they develop into squamous cell cancers or benign tumours. For example, suprabasal β1 integrin expression, as seen in some squamous cell carcinomas, activates extra-cellular signal regulated kinase (ERK) in basal and suprabasal keratinocytes and profoundly affects the susceptibility of the underlying proliferating cells to chemical carcinogenesis. I present the results of experiments using transgenic mice, hereafter referred to as InvEE, that express activated mitogen activated protein kinase kinase-1 (MEK1) in suprabasal layers of the epidermis resulting in constitutive ERK overexpression and results in increased keratinocyte expression of interleukin- 1a (IL-1 alpha), triggers epidermal hyperplasia, skin inflammation and benign tumours. Methods: I developed a protocol for inducing tumour formation in InvEE mice by full-thickness skin punch biopsy. I negated the affect of IL-1 alpha activation of inflammatory cells by generating InvEE bone marrow chimeras using MyD-88-/- mice or litter-mate InvEE mice as a control. InvEE/InvEE and InvEE/Myd- 88-/- chimeric mice were wounded and observed for tumour formation for 60 days. The experiment was conducted twice and the number of tumours in each group was analysed using a chi-squared test. Results: Spontaneous benign tumours occurred in 27 of 295 (9%) InvEE mice correlating with cutaneous injury. Punch-biopsy wounding induced tumours after 3–4 weeks in 37 of 92 (40%) InvEE mice compared to no tumours in 40 (0%) wild-type litter-mates (p<0.0001). The percentage of wound-induced tumours in bone-marrow chimeras of InvEE/InvEE and InvEE/MyD-88-/- was 40% and 8% respectively (p<0.005). Resident inflammatory cells demonstrated differential responses to wounding in InvEE/MyD-88-/- chimeric skin. Conclusions: This study demonstrated that inhibition of IL-1 alpha signalling from MEK1-activated keratinocytes prevented tumour formation in a chronic inflammatory microenvironment. No significant financial relationships to disclose.
Successful changes in the diagnosis of earlier stages in invasive cervical cancer following a cancer detection program in Tucuman, Argentina
Authors: Zarba J. J. , Holgado S. V. , Segura M. Sanchez , Gonzalez A. , Audi V. , Elias A. 
Published: March 2020

1544 Background: The PDCCUT provides annually free cancer screening to many low-income, underinsured women. Effective control of cervical cancer depends primarily on early detection of precancerous lesions and also on the diagnosis of earlier stages of invasive lesions through use of the Papanicolaou test, followed by timely evaluation and treatment. The goal of this study is to determine the impact of the PDCCUT on the stage at initial diagnosis of invasive cervical cancer. Methods:This is a retrospective, cross-sectional and exploratory study of data registered in CRRCGMT from 376 women with cervical cancer diagnosis. UICC/FIGO is the staging system used. Every 3 years -from 1985 to 2005- rates were calculated; also trend of stages I-IIa and IIb-IV were estimated. Patients-stages were analyzed, before and after 2001 (beginning of the program). Changes in cervical cancer rates before and after the introduction of organized screening were compared. Conclusion: The results showed a progressive increase in the diagnosis of earlier stages of cervical cancer indicating the impact of PDCCUT. The last trienium rate is coincident with the increase of citological diagnosis (Papanicolaou). A lower rate in the diagnosis of EIIb-IV stages is expected in the next trienium. Evaluation of clinical practice in a Cancer Program allows to improve asistencial quality. [Table: see text] [Table: see text] No significant financial relationships to disclose.
The accuracy of colposcopy in diagnostic and screening settings
Authors: Cantor S. B. , Cárdenas-Turanzas M. , Follen M. , Cox D. D. 
Published: March 2020

1545 Background: We sought to determine the accuracy of colposcopy to diagnose cervical precancer in screening and diagnostic settings. Methods: As part of a larger clinical trial, 1850 patients were recruited into a diagnostic group or a screening group depending on their history of abnormal Papanicolaou smear results. For all patients, colposcopic examination was performed and biopsies were obtained from abnormal and normal colposcopic sites. The gold standard of test result accuracy was the histologic report of biopsies. Results: The diagnostic group had a 29.0% prevalence of high-grade squamous intraepithelial lesions (HGSIL) or cancer, and the screening group had a 2.2% prevalence of HGSIL or cancer. Using a disease threshold of HGSIL or worse, the diagnostic group had a sensitivity of 71.4% and a specificity of 81.3%, and the screening group had a sensitivity of 19.1% and a specificity of 96.1%. The areas under the receiver operating characteristic (ROC) curves for the diagnostic and screening groups at the same disease threshold were 0.854 and 0.511, respectively. Conclusions: We demonstrated that colposcopy performs well in the diagnostic setting and poorly in the screening setting. Colposcopy should not be used for the screening of cervical intraepithelial neoplasia. No significant financial relationships to disclose.
Tobacco use among individuals presenting for cancer risk assessment
Authors: Shen W. , Ross L. F. , Patrick-Miller L. , Olopade O. I. , Cummings S. A. , White M. A. , Dudlicek L. , Bradbury A. R. 
Published: March 2020

1547 Background: An important component of cancer risk assessment (CRA) is the evaluation of exposures and preventive health behaviors. Tobacco use (TU) remains a significant contributor to cancer risk and decreasing tobacco use is a major national health objective. Methods: Clinical charts were reviewed to evaluate the incidence of TU and characteristics of tobacco users (TUs) among individuals presenting to the University of Chicago Cancer Risk Clinic for cancer risk assessment (CRA). Results: Among 98 individuals (97% female) presenting for CRA from 12/05–10/06, 51% (50/98) reported no TU, 38% (37/98) reported prior TU and 11% (11/98) reported current TU. Current tobacco users included 10% (7/73) of whites and 18% (4/22) of blacks with no TU among other racial groups (0/3). 45% of TUs (5/11) had a personal history of cancer. 45% of TUs reported compliance with self-breast examination, 73% with cervical cancer screening. Among TUs over 40 years old (YO), 67% (6/9) reported a mammogram in the last year and the 2 TUs over 50 YO reported a screening colonoscopy. All TUs reported interest in tobacco cessation interventions. Conclusions: Tobacco use among individuals presenting for CRA is lower than reported general population rates of TU (23%). Despite this, a proportion of individuals presenting for CRA report current TU, despite engaging in other cancer prevention behaviors. Continued review of clinical encounters from 2004- 06 (n=425) will allow for multi-variate analysis of predictors of current TU, which will inform future research employing cancer risk assessment encounters as “teachable moments” to optimize tobacco cessation outcomes. No significant financial relationships to disclose.
Frequency and accuracy of the first-degree family history of cancer in a community-based sample of women with low literacy in the South of Brazil
Authors: Roth F. L. , Bochi C. , Palmeiro E. I. , Kalakun L. , Callefi M. , Giugliani R. , Prolla P. A. 
Published: March 2020

1549 A positive family history (FH) in first-degree relatives (FDR) is one of the most important risk factors for breast cancer. However, there are few published studies about its prevalence in community-based samples. The aim of this study was to evaluate the prevalence of first-degree cancer FH in an unselected sample of low-literacy women recruited in primary-care health centers through an interview and questionnaire. Accuracy of self- reported cancer history in a FDR was also evaluated. Of 6514 women, 4.5% were illiterate and 66% had elementary education. When asked about cancer FH, 23.3% had at least one FDR with cancer. The accuracy of reported FDR history was evaluated by telephone 12 months after the initial interview. Of the 1516 women reporting at least one FDR with cancer, a random telephone contact was made with 710 (46%). In 88% of the patients, the history reported by phone was exactly the same as the one reported initially. In addition, 29 of 710 patients contacted by phone denied cancer history in FDR. In 7.9% of the patients, FDR history of cancer was confirmed, but one of the following inconsistencies in relation to the original report was described: the type of cancer was different or the relative affected was different. We conclude that a significant proportion of women report history of cancer in a FDR accurately, despite of low literacy. These findings have considerable relevance to clinical practice and are important to validate FH taking in cancer risk estimation models that use this variable. No significant financial relationships to disclose.
Classification of renal cell carcinoma (RCC) based on the expression of VEGF and its receptors on tumor cells and microvessels: Identification of subsets with distinct patterns of expression, microvessel density, and outcome
Authors: Camp R. L. , Siddiqui S. F. , Kelly W. K. , Uchio E. , Kluger H. M. 
Published: March 2020

15503 Background: The recent development of anti-angiogenic therapy for RCC has significantly improved the treatment of these often refractory tumors. However not all patients respond to therapy and assays for predicting outcome are needed. As a first step, we analyzed a retrospective cohort of tumors and assessed the ability of VEGF and VEGF receptors (VEGF-Rs) to classify tumors. Methods: Tissue microarray analysis of 330 RCC (clear cell = 234, papillary = 46) was performed using a novel method of Automated Quantitative Analysis (AQUA) of VEGF and VEGF-Rs (R1, R2 & R3) expression by fluorescent immunohistochemistry. The expression of VEGF and VEGF-Rs were separately quantitated within tumor cells, endothelial cells, and adjacent normal epithelium. Expression was recorded on a continuous scale and represents the average of two histocores. Results: VEGF and VEGF-Rs exhibited distinct expression patterns on tumor cells, tumor endothelium, and adjacent normal tissue. Within each component, expression of VEGF and its receptors was tightly correlated (all p-values < 0.001). Although tumor cell expression of VEGF did not correlate with microvessel density (p- value = 0.1848), tumor cell expression of R1 and R2 were strongly and inversely correlated with microvessel density [p-values <0.0001]. Unsupervised hierarchical clustering classified tumors according to the coordinated expression of VEGF and VEGF-Rs within the three tissue components - tumor (T), normal (N), and vessel (V). Tumors were classified into 5 clusters: 1) high T, N & V; 2) low T, high N & V; 3) high T, low N & V; 4) low T, N & V; and 5) high T & N for R3 only. Of these, clusters 1 and 3 exhibited poor survival, whereas clusters 2 and 4 contained tumors with high vessel densities. The distribution of clear cell and papillary tumors was not significantly different between clusters. Conclusions: VEGF and its receptors exhibit a complex pattern of coordinated expression in RCC. Clustering of tumors based on VEGF and VEGF-R in tissue components may provide a prognostic assay as well as a means for determining which tumors will respond to what anti-angiogenic therapies. No significant financial relationships to disclose.
Identification of ABCA5 as a tissue and urine diagnostic marker for PIN
Authors: Stearns M. E. , Hu Y. , Wang M. , Veverka K. A. 
Published: March 2020

15508 Background: Bostwick and colleagues have suggested that prostatic intraepithelial neoplasia or PIN is the precursor of prostate cancer, and that a significant percentage of men with PIN develop prostate cancer (Sakr, 1994; Bostwick, 1995b; Arakawa, 1995; Qian, 1995; Qian, 1997). Currently there are no molecular diagnostic markers for PIN. Methods: Recently, we have developed ‘DNA-protein’ binding assays for the identification of novel transcriptional regulatory proteins associated with PIN glands. Electrophoretic mobility shift assays (EMSAs) with the 32P-labeled DNA probe was used for analysis of protein extracts from tissues and urine. Immunolabeling was carried out with rabbit antibodies specific for ABCA5. Results: Electrophoretic mobility assays (EMSAs) revealed that 1 DNA sequence (1 of 4,096 sequences screened) specifically bound a ∼160 Kda protein which was over-expressed in PIN and not found in BPH, SV or PCA glands (n=11). The gene encoding for the 160 Kda protein was cloned from a cDNA expression library by ‘in situ’ hybridization assays with the 32P-labeled DNA sequence. Sequencing revealed that the gene encoding for the 160 Kda protein was ABCA5, a member of the superfamily of ATP-binding cassette (ABC) transporters of multi-drug resistant genes. RT-PCR assays indicated the mRNA was over-expressed in PIN tissue, and was not present in BPH, or SV tissue. Rabbit polyclonal antibodies and immunolabeling showed that the antibodies specifically labeled the cell junctions of 3% glutaraldehyde fixed prostate cells. Immunohistochemistry indicated that ABCA5 was over expressed in foci of intermediate basal cells in normal glands, and in HGPIN. ABCA5 was faintly expressed in PCA glands. Enzyme linked immunoabsorbent assays (ELISAs) demonstrated in blinded studies that ABCA5 was a highly sensitive (>98% sensitivity) urine diagnostic marker for HGPIN in biopsy positive patients (n=107) at a cut off” of 25 ng/ml. ABCA5 was present at very low levels (i.e. <25 ng/ml) in the urine of patients diagnosed with BPH (n=79) or prostatitis or kidney and bladder cancer (>86% specificity). Conclusions: The data suggest that the expression of ABCA5 is over-expressed by PIN and may be a highly sensitive and specific urine diagnostic marker for detection of early stage prostate cancer. No significant financial relationships to disclose.
Correlation of preoperative citology/histology in radiologically detected lesions and histologic findings at excision
Authors: Manente P. , Vicario G. , Scelzi E. , Sartor L. , Nicolardi L. , Rizzo A. , Pinarello A. , Spaliviero B. , Sbeghen R. 
Published: March 2020

1552 Background: The major techniques used to diagnose breast abnormality has been for many years fine-needle aspiration (FNA) cytology and core needle biopsy (CNB) and more recently vacuum-assisted core biopsy (VACB). These techniques are accurate and allow definitive therapeutic surgery. The aim of our study was to detemine whether cytology/histologic findings mach histologic findings at excision. Methods: In our Institution, between January 2004 and June 2006, 43,138 mammographic exams were performed. 1,012 patients had patological lesions at mammography: 617 FNA cytology ( C due to European guidelines for breast cancer screening assessment) and 395 CNB/VACB (B) were performed. Patients with respectively suspicious and malignant FNA cytology (C4 and C5) and respectively uncertain malignant potential, suspicious and malignant histology (B3, B4 and B5) underwent to surgery. Results: The number of cancer identified by FNA cytology was 158 and the number of cancer identified by CNB/VACB was 253. The correlation of preoparative citology/histology with definitive histology had showed: false negative rate respectively 0.79% for histology (B) and 3.16% for cytology (C). False positive rate was respectively 0.4% for B and 0.63 for C. Complete sensitivity was 98.2% for B and 89.87% for C. Absolute sensitivity was 90.51% for B and 76.58% for C. Conclusions: Our data demostrated very high performance of diagnostic preoperative procedures due to multidisciplinary approach between the radiologists, the clinicians and the pathologists. No significant financial relationships to disclose.