bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and function of the four and a half LIM-only protein 2 (FHL2) in breast cancer
Authors: Martin B. T. , Kleiber K. , Kaufmann M. , Strebhardt K. 
Published: March 2020

10109 Background: FHL2 belongs to the expanding family of proteins that possess highly conserved double Zn-finger motifs, CX2CX16–23HX2CX2CX2CX16–21CX2 (C/H/D), and are involved in protein-protein interactions and transcriptional regulation. FHL2 was primarily described as “down regulated in rhabdomyosarcama cells LIM domain protein” (DRAL). Further studies also indicated a connection of FHL2 with the tumor biology. Its expression has been shown to be increased in tumors of epithelial and melanoma cell origin. A recent publication describes the interaction of FHL2 with the breast cancer susceptibility gene 1 (BRCA1) but to date little is known about the function of FHL2 in breast cancer. Methods: Tumor samples of 61 breast cancer patients and 8 normal breast tissues were lysed and subjected to Western blot analysis using a monoclonal FHL2-specific antibody; Tissue specimens of normal breast and breast cancer were histologically examined with the monoclonal antibody used for the Western blot analysis; Luciferase assays were carried out in MCF-7 breast cancer cells, using AP1-dependent reporter plasmids. Anchorage-independent growth was assayed by colony formation in soft agar. Results: FHL2 is overexpressed in almost all human breast cancer tissues tested but not in normal breast tissues and only low levels of FHL2 expression were present in four premalignant ductal carcinoma in situ (DCIS). Co-immunoprecipitation assays and GST-pull down experiments revealed that FHL2 interacts with the proto-oncogene c-jun in breast cancer cells. Reporter gene assays demonstrated that FHL2 represses c-jun-mediated activation of an idealized AP-1-regulated reporter gene in a dose-dependent manner. This repression was also seen on the naturally occurring AP-1-dependent IL2 promoter. The repression domain was identified within the N-terminal half of the FHL2 molecule. Finally, we show that stable expression of FHL2 leads to anchorage-independent growth of breast cancer cells in soft agar. Conclusions: Taken together, our data suggest that by modulating the activity of transcription factors such as c-jun, the expression of FHL2 in breast cancer might contribute to the malignant potential of breast tumors. No significant financial relationships to disclose.
The role of vitamin E in the prevention of cancer: Meta-analysis of randomized controlled trials
Authors: Alkhenizan A. , Hafez K. 
Published: March 2020

1017 Background: Several in vitro studies showed antioxidant vitamins to have a significant protective effect against cancer. We did a meta-analysis of Randomized Controlled Trials (RCTs) to evaluate the role of vitamin E supplements in the prevention of Cancer in adults Methods: We included RCTs, in which outcomes of the intake of vitamin E supplement alone or with other supplements, were compared to a control group.The primary outcomes were total mortality, cancer mortality, total incidence of Cancer, incidence of Lung, stomach, esophageal, pancreatic, prostate, breast and thyroid cancers. All identified trials were reviewed independently by the two reviewers to determine whether trials should be included or excluded. The quality of all included studies was scored independently by the two reviewers. RevMan, version 4.2 was used for the data analysis. Results: Twelve studies met inclusion criteria, including 167025 participants. There were no statistically significant differences in total mortality (RR 0.99; 95%CI 0.96–1.03), cancer incidence (OR 0.96; 95%CI 0.92, 1.01), and cancer mortality (OR 1.00; 95%CI 0.96–1.03) among the different groups of patients included in this meta-analysis. Vitamin E did not reduce the incidence of any type of cancer that was available for analysis; However there was a statistically significant reduction in the incidence of prostate cancer in patients receiving vitamin E, RR 0.85 [0.73–0.96, NNT=500]. Conclusions: Vitamin E supplementation was not associated with a reduction in total mortality or cancer incidence, and cancer mortality, but it was associated with a statistically significant reduction in the incidence of prostate cancer. Vitamin E can be used in the prevention of Prostate cancer in men who are at high risk of prostate cancer. No significant financial relationships to disclose.
Preferences for cancer prevention strategies (CPS) in women with hereditary nonpolyposis colectal cancer (HNPCC)
Authors: Sun C. C. , Peterson S. K. , White K. G. , Watts B. G. , Daniels M. S. , Boyd-Rogers S. G. , Schmeler K. M. , Bodurka D. C. , Lu K. H. 
Published: March 2020

1018 Background: Women with HNPCC have 40–60% lifetime risk of endometrial and colon cancer (CA) and 10–12% risk of ovarian CA. Because CPS have significant QOL implications, understanding how women evaluate CPS and personal risks of CA may facilitate physician and pt communication for medical decision making in this group of pts. Methods: Using the visual analog scale (VAS) and standard gamble (SG), women with HNPCC or with a family history (FHx) that fulfilled Amsterdam II criteria were asked to: 1) score CPS from 0.0=worst to 1.0=best; and 2) state the % personal risk of CA they would need to have in order to undergo each CPS. CPS included oral contraceptives ± COX-2 inhibitors (OC ± COX2); endometrial biopsy/transvaginal ultrasound/CA125 ± colonoscopy (Bx/US ± CSPY); pre- and post-menopausal total abdominal hysterectomy/oophorectomy ± subtotal colectomy (TAH/BSO ± COL). Results: To date, 32 women have enrolled (median age=38.4 yrs). Bx/US + CSPY was rated most favorably (0.95) followed by OC, Bx/US, and CSPY(.90). Pre-menopausal TAH/BSO, COL, and TAH/BSO+ COL had the least favorable ratings (0.50, 0.30, and 0.25, respectively). Women accepted non-surgical CPS if their personal risk of CA was at least 30%; pre- and post-menopausal TAH/BSO if the personal risk of CA was at least 73% and 50%, respectively. Women accepted COL and TAH/BSO + COL if their risks of CA were at least 78% and 80%, respectively. Women without FHx of HNPCC-gynecologic (GYN) CA would participate in all CPS more readily than women with FHx of HNPCC-GYN CA. Specifically, to accept COX2, women without FHx of HNPCC-GYN CA would do to if their personal CA risk was at least 10% compared to a 30% risk for women in the 2nd group (p=.04). For the 2 groups, risks for Bx/US, pre-menopausal TAH/BSO, post-menopausal TAH/BSO, TAH/BSO + COL and COL were 20% vs 30% (p=.06), 40% vs 80% (p=.03), 30% vs 55% (p=.02), 65% vs 80% (p=.06), and 80% vs 100% (p=.01), respectively. Conclusions: Our data indicate that women without FHx of HNPCC-GYN CA are more willing to undergo chemoprevention, screening and prophylactic surgery for HNPCC CA compared to women with a FHx of HNPCC-GYN CA. This may be due to the perception of a more favorable clinical outcome associated with endometrial CA, the more common of the HNPCC-GYN CA. No significant financial relationships to disclose.
Patterns of diagnosis for colorectal cancer (CRC): Screening detected versus symptomatic presentation
Authors: Smiljanic S. R. , Gill S. 
Published: March 2020

1023 Background: Colorectal cancer (CRC) is a leading cause of cancer death in North America; studies have shown that screening improves survival. Conducted in British Columbia, Canada, this study was conducted to identify the proportion of screening-eligible patients with sporadic CRC who are detected by screening tests versus symptomatic presentation,and to compare baseline patient and tumor characteristics of these two groups. Methods: This retrospective cohort study identified 571 cases via the BC Cancer Registry of patients age 50 years and older presenting with first diagnosis of invasive CRC between Nov. 2002 and Apr. 2003. Patients with non-adenocarcinoma histology, HNPCC or FAP were not included. Self completed questionnaires were mailed to all patients to capture: prior screening history, screening versus symptomatic presentation, and demographic information. All respondents charts were then reviewed to corroborate screening information, and to obtain pathological information including TNM stage, grade and site (proximal versus distal colon versus rectal). Results: Of 212 eligible respondents (37% response), only 14 of 212 (6.6%) patients with a new CRC were detected via screening versus 198 of 212 (93.4%) presenting with symptoms. Respondents were average age at diagnosis 69 years, 59% male, 91% Caucasian, 37%rectal, and 18% M1 at diagnosis. No significant differences in the age, gender, ethnicity, socioeconomic status, tumour stage and site were detected between the screened versus symptomatic groups. Only 33 of 212 patients (15.6%) reported ever having a screening test. 19 of 198 cancers (9.6%) were diagnosed by symptomatic presentation despite a compliant screening history. Conclusion: Despite universal health-care access in British Columbia, only 7% of patients with a new diagnosis of CRC were detected via a screening test. Furthermore, only 15% of screening-eligible respondents have ever been screened. There were no differences in patient demographics or stage of disease at presentation but numbers in the screening cohort were limited. Significant effort is required to increase knowledge and compliance for CRC screening. No significant financial relationships to disclose.
Incidence of reversible amenorrhea in women with early-stage breast cancer undergoing adjuvant anthracyclin-based chemotherapy with or without docetaxel
Authors: Berliere M. , Dalenc F. , Malingret N. , Vindevogel A. , Kerger J. , Roche H. , Symann M. , Donnez J. , Machiels P J. 
Published: March 2020

10517 Background: The objective of this study was to determine the incidence of reversible amenorrhea in women with early-stage breast cancer undergoing adjuvant anthracyclin-based chemotherapy with or without docetaxel. Methods: We studied the amenorrhea duration induced by 2 chemotherapy regimens. The first arm (6FEC) consisted in the administration of 6 cycles of FEC100 (5-Fluorouracil 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2, day 1, every 3 weeks) and the second arm (3FEC/3D) in the administration of 3 cycles of FEC100 followed by 3 cycles of Docetaxel (100 mg/m2, day 1, every 3 weeks). Some of these patients (N = 121, 78%) were treated in the PACS01 trial that was designed to evaluate the impact of the sequential addition of docetaxel to FEC100 on disease-free survival for patients with node positive, operable breast cancer. Other patients (N = 33.22%) were patients treated with the same regimens after the inclusion period of PACS01. Reversible amenorrhea was defined as a recovery of regular menses and -when available (101 patients)- premenopausal hormonal values (minimum 2 tests at 3 months interval) in the year following the end of chemotherapy infusion. Results: 154 pre-menopausal patients were included: 84 were treated in the 6FEC and 70 in the 3FEC/3D. Median age was 43.5 (28–58) and 44 (29–53), respectively. The incidence of chemotherapy-induced amenorrhea at the end of chemotherapy was not different between the two groups, 6FEC: 93% and 3FEC/3D: 92.5%. In the year following the end of chemotherapy, more patients recovered regular menses in the 3FEC/3D arm compared to the 6FEC arm: 35.5% (25/70) versus 23.7% (20/84) (p = 0.019). For the 101 for which hormonal values were available, more patients recovered premenopausal hormonal values in the 3FEC/3D arm: 42% (18/42) versus 29% (17/59) (p < 0.01). Conclusions: Our study suggests that it could be interesting to record the menopausal status at different time points after the end of chemotherapy. In addition, the survival advantage in the PACS01 trial in favor of the 3FEC/3D arm was observed only for women over the age of 50 and not for women younger than 50. In this context, the clinical relevance of reversible amenorrhea warrants further investigation. No significant financial relationships to disclose.
Is histology (His) relevant in adjuvant (Adj)/neoadjuvant (NA) therapy of breast cancer (BC)?
Authors: Katz A. , Saad E. D. , Pusztai L. 
Published: March 2020

10541 Background: Invasive lobular carcinoma (ILC) constitutes 10–15% of cases of invasive BC. In ongoing NCI-sponsored, randomized trials (RT) of early BC, His is not a stratification factor, despite the suggestion that ILC might have distinct clinical behavior and gene expression profile. Compared with invasive ductal carcinoma (IDC), ILC is more frequently of lower grade and positive for estrogen receptor (ER). Methods: We reviewed the literature to evaluate the effect of His on outcome of Adj and NA therapy, by quantifying its impact on the pathologic response (pCR) rate to NA chemotherapy (CT), and on the results of adjuvant trials. We also compiled retrospective series analyzing pCR to NA CT according to His. Results: We retrieved 16 RT (8 phase III, 8 phase II) of NA therapy; 11 compared CT regimens, 3 regimens that contained CT and hormone therapy (HT), and 2 HT only. None of the RT used His for stratification; 5 studies described His at randomization, but only 1 provided information on pCR rate to CT according to His (Dieras et al, 4.0% for ILC, 8.3% for IDC). Compiled results of 6 retrospective series which included nearly 3,000 patients (PTS) showed a pCR rate of 1.7% (6 of 354) in ILC PTS and of 11.6% (300 of 2584) in IDC PTS (P < 0.01). Of 39 phase III RT of Adj CT, 7 compared CT vs HT, 14 CT vs CT + HT, 11 HT vs HT + CT, and 7 CT vs HT vs CT + HT. Of the 39 RT, only 4 described His in demography (9%, 9%, 10% and 12% of PTS participating in these 4 RT were ILC), but none analyzed results according to His. Conclusions: We suggest that the role of CT in early ILC is not clear. The pCR rate is significantly lower in ILC PTS treated with NA CT. It is also not clear if His is an independent predictive factor or a marker of grade/ER expression. The specific value of CT in the Adj treatment of ILC PTS has not been adressed in the Adj RT. Past and current, ongoing RT of Adj CT do not stratify PTS according to His neither evaluate the results according to His. Given the potential therapeutic implications, we suggest that the role of His should be more thoroughly investigated in future RT in order to define the appropriate effectiveness of CT and HT in the treatment of ILC PTS, so that possible overtreatment of ILC PTS with CT might be avoided. No significant financial relationships to disclose.
Phase II study of sequentially administered mitomycin (MMC) and irinotecan (CPT-11) in patients (pts) with metastatic breast cancer (MBC)
Authors: Mrozek E. , Kolesar J. , Allen J. , Young D. , Angus D. , Kendra K. , Rhoades C. A. , Villalona-Calero M. A. , Shapiro C. L. 
Published: March 2020

10542 Background: MMC and CPT-11 are synergistic in preclinical studies, as MMC increases expression of Topoisomerase I (Topo I), the target of CPT-11. Three out of 5 heavily pretreated MBC pts benefited from MMC and CPT-11 in a phase I trial. We designed a phase II trial of this combination in MBC pts and hypothesized that increased Topo I expression in peripheral blood mononuclear cells (PBMC) would correlate with longer time to progression (TTP). Methods: Pt eligibility: ECOG PS 2 or less; no more than 2 prior chemotherapy regimens for MBC; adequate organ function; measurable and non-measurable disease were permitted. Treatment: intravenous (IV) MMC-6 mg/m2 on day 1 and IV CPT-11–125 mg/m2 on days 2 and 8 every 28 days. Genotyping of NQ01 (enzyme that activates MMC) was evaluated by pyrosequencing; Topo I gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) was evaluated in PBMC pretreatment, 24 hrs, 48 hrs, and 8 days after MMC. Results: Thirty-two pts enrolled with the following characteristics: median age 50 years (range 29–73); median PS 0 (range 0–2); postmenopausal 29 (91%) pts; estrogen receptor (ER) negative 14 (44%) pts; HER-2/neu 3+ by IHC 7 (22%) pts, and 10 (31%) pts were ER(−), PR(−) and HER-2/neu (−). Six (19%) pts had no prior chemotherapy; 7 (22%)-1 prior regimen; and 19 (59%)-2 prior regimens. Pts received a median of 4 cycles (range 1–12). Four (12%) pts experienced grade 4 toxicity (1-neutropenia without fever, 1-abdominal pain, 1-pulmonary embolism, and 1-diarrhea). The most common grade 3 toxicities were neutropenia in 13(41%) pts, nausea in 7 (22%) pts, diarrhea in 6 (19%) pts, fatigue in 5 (16%) pts, and thrombocytopenia in 2 (6%) pts. Median TTP was 4.7 months (95% CI, 4.0 to 5.4 months). For 10 triple negative pts the median TTP of 5.4 months was not different. Baseline and induced Topo I gene expression was greatest in NQ01 wild-type genotype, however, increased Topo I expression in PBMC was associated with shorter TTP. Conclusions: Sequential administration of MMC and CPT-11 had acceptable toxicities and antitumor activity. Our hypothesis that increased Topo I expression in PBMC correlates with longer TTP was incorrect. No significant financial relationships to disclose.
Induced fluorescence of breast cancer in the mouse model: A simple technology to improve visualization of malignant tissue during breast cancer surgery
Authors: Chan A. D. , Luiken G. A. , Quigley M. M. , Xu M. , Hoffman R. M. 
Published: March 2020

10557 Background: Accurate identification of all malignant tissue at the time of lumpectomy or mastectomy can at times be challenging. When positive margins are discovered, significant additional time and effort may be required by the surgeon to complete the initial procedure. Inducing the cancer cells to be fluorescent offers the potential to improve the surgeon’s ability to rapidly and accurately identify and excise the malignant tissue at the time of surgery. We have previously demonstrated the feasibility of inducing tumor fluorescence with fluorophore-tagged anti-tumor antigen antibodies using a human colon cancer cell line. We present here our recent results using a human breast cancer cell line in the nude mouse. Methods: A human breast cancer cell line, MDA-MB-468 known to express CA 15–3 was used. Breast cancer cells were subcutaneously implanted in 14 nude mice. Three to five weeks after injection, tumor nodules were easily visible and palpable. Using the tail vein method, mice were injected with fluorophore-tagged anti-CA 15–3 and were examined using a small animal imaging system with a 470 nm light source. Mice were also examined using a simple blue LED flashlight fitted with a fixed 470 nm band-pass filter and were observed through filtered goggles. Results: Tumor nodules could be seen to fluoresce through the skin when illuminated with a 470 nm light source. When tumor nodules were exposed and examined with white light, the nodules could be seen but when illuminated with the 470 nm light source, tumor fluorescence allowed clear identification of nearby small tumor nodules and clear identification of tumor margins easily distinguishable from the normal tissue. Conclusions: For this technology to work, tumor antigens must be known and antibodies to these antigens available. It is easy to perform, requires no complex equipment or operator expertise and could be easily adapted to surgical oncology in any hospital setting. It has the potential to improve surgical accuracy in women undergoing initial lumpectomy or mastectomy as well as axillary lymph node dissection or sentinel node biopsy. In addition it could aid in the surgery of patients undergoing resection of isolated recurrent hepatic or pulmonary metastases. No significant financial relationships to disclose.
Toll like receptor 3 expression and efficacy of adjuvant treatment with polyadenylic-polyuridylic acid in patients with axillary node positive breast cancer: Results from two randomized trials
Authors: André F. , Massard C. , Assi H. , Besse B. , Sabourin J. , Zitvogel L. 
Published: March 2020

10563 Background: Toll like receptor 3 (TLR3) are transmembrane receptors involved in the cellular response to danger signal and specifically activated by double stranded RNA. Based on these data, we hypothesized that the TLR3 expression by tumor cells is associated with the efficacy of a treatment with double stranded RNA in cancer patients. Patients and Methods: TLR3 expression was assessed by immunohistochemistry in 336 patients with axillary node positive breast cancer. These patients were selected to have been included in two randomized trials that compared a post-operative administration of polyadenylic-polyuridylic acid (polyAU) to either no treatment (n = 174, trial I) or an adjuvant chemotherapy by CMF regimen (n = 162, trial II). In the trial II, locoregional and pelvic radiotherapy were given in the polyAU arm. Results: TLR3 was found to be overexpressed in 45 tumors (13%). Median follow-up were 23 and 17 years for living patients included in the trials I and II respectively. When the analysis focused on the first trial, the 20 year overall survival rates were 87% (95% CI: 53–97%) and 32% (95% CI: 12–63%) for patients with TLR3-overexpressing tumour treated (n = 8) or not (n = 11) with polyAU (p = 0.03). In the same trial, the 20 year overall survival rates were 43% (95% CI: 33–54%) and 35% (95% CI: 25–46%) for patients with TLR3-negative tumor treated (n = 81) or not (n = 74) with polyAU (p = 0.32). When the analysis focused on the Trial II, the 15 year overall survival were 62% (95% CI: 45%-91%) and 21% (95% CI: 8%-47%) for patients with TLR3-overexpressing tumors treated (n = 12) or not (n = 14) with polyAU (p = 0.005). In the same trial, 15 year overall survival rates were 31% (95% CI: 21%-42%) and 39% (95% CI: 28%-51%) for patients with TLR3-negative tumors treated (n = 66) or not (n = 70) with polyAU (p = 0.39). Conclusion: This study suggests that the post-operative administration of polyadenylic-polyuridylic acid improves outcome of patient with TLR3-overexpressing, node-positive breast cancer. [Table: see text]
National HER2 testing program for breast cancer patients in Argentina
Authors: Frahm I. 
Published: March 2020

10566 Background: In Argentina, before 2003 few pathologists performed HER2 testing, using different non-standardized Inmuno-Histo-Chemical (IHC) methods with dubious and non-reproducible results and also leaving some parts of the country without HER2 diagnosis Objective: HER2 has a key role in breast cancer management, so the aim of the study was to settle a National HER2 testing Program to permit access to standardized HER2 detection all over the country, and whenever possible, to determine hormonal receptors. Methods: In August 2003, 13 pathologists formed a cooperative group and created a national framework to train and set HER2 diagnostic centres in each country region. A coordinator responsible for coaching and evaluating centres and two technical consultants in charge of quality control and technique standardization were designated. In February 2004, the program was launched. Tumors were received from 82 oncologists and breast surgeons, using a private courier created “ad hoc”. HER2 was analyzed by IHC test between February 2004 and November 2005 and performed using policlonal antibody anti Her 2 (DAKO), microwave antigenic recovery, detection system EnVision (Dako) and developed with diaminobenzidine. Results were interpreted as HercepTest guidelines. ER/PR were screened by IHC analyses. Results: 2285 HER2 tests were performed: HER2 was over-expressed (score 3+) in 18% of tumors (408). 136 (6%) samples were score 2+, 407 (18%) score 1+ and 1334 (58%) score 0. In 1532/2285 (67%) of tumor specimens ER and PR status could be determined. Conclusions: Founding HER2 National Program allowed access to HER2 testing all over the country with a standardized and reproducible technique. HER2 prevalence in our sample (18%) is similar to those previously published. Although international algorithms recommend FISH assay to HER2 2+ tumors, our Program can not afford it. ER/PR expression were decreased significantly in HER2 3+ vs. HER2 - tumors: 53% vs. 64%: p = 0.002. HER2 3+ were associated with higher levels ER/PR: 38% vs. 24% in HER2 - tumors (p < 0.001). [Table: see text] No significant financial relationships to disclose.