bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of acute doxorubicin exposure on caspase-mediated apoptosis in cardiomyocytes.
Authors: Demirci Umut , Yaman Melek , Bagriacik Umit E.
Published: March 2020

e12036

Background: Doxorubicin binds to DNA-associated enzymes, intercalates the base pairs of the DNA and induces apoptosis in cancerous and healthy tissues especially in cardiomyocytes. Caspase mediated apoptosis in cardiomyocytes remains largely unknown. We investigated the role of doxorubicin via caspase system on apoptosis of cardiomyocytes. Methods: H9C2ratcardiomyocytes were incubated with doxorubicin a concentration of 10-6 Mfor 4 or 24 hours to perform gene expression and activity of caspases, respectively. Total RNA isolated and expression analysis were performed by real time PCR assay. Caspase activity was determined by colorimetric caspase assay kit. At least two fold increases in gene expression were accepted statistically significant. Results: In comparison to controls, bothof caspase expression and activity increased in doxorubicin-treated samples. Increase in expression of Caspase 9 and 2 as initiator caspases and caspases 7 and 3 as effector caspases were detected statistically higher than control values. In contrast, expression of caspase 1, 4, 6, 8 and 12 were detected lower than controls. Activity of both caspase 3 and 9 increased significantly. Conclusions: Acute doxorubicin administration caused a significant caspase activation on apoptosis of cardiomyocytes.
Triple negative breast cancer in African American women: Disparity between women in New Orleans versus Louisiana.
Authors: Loch Michelle Marie , Estrada John , Reske Thomas , Li Xiangrong , Chen Vivien , Wu Xiao-cheng
Published: March 2020

e12501

Background: For years clinicians have made the empirical observation that there is an unusually high number of African American women (AAW) with triple-negative (Tneg) breast cancer (BC) in New Orleans (NO). Knowing the rate of Tneg BC in AAW is higher than white women (WW), we explored the hypothesis that AAW in NO have a higher rate of Tneg BC when compared to AAW in the rest of Louisiana (LA). Methods: We analyzed data from the Louisiana Tumor Registry, one of the NCI funded SEER registries, for the tumor characteristics of invasive female BC diagnosed in 2010, focusing on racial disparities; HER2 status was not available for prior to 2010 diagnosis. We explored the association of HER2 status with age, race, ER, PR, HER2, T, N, M to determine crude and adjusted odds ratios and rate distribution of subtypes using SEER*Stat and SAS programs. Results: Overall age-adjusted incidence rate of Tneg BC in AAW was 30 per 100,000 in NO, which was 24% higher than that in AAW in the rest of LA and two-fold the rate in WW of both NO and LA. The highest rate of Tneg BC was seen in AAW aged 65-69 in NO (184.97 per 100,000) compared with 81.5 per 100,000 in AAW aged 55-59 in LA. AAW with Tneg BC in NO were more likely to have more aggressive BC. Young age, black race, large tumor size, higher grade and TNM stage were significantly associated with the high risk of Tneg BC. After adjusting for age, geographic area, and other tumor characteristics, the higher risk of Tneg BC in AAW remained in NO compared with the rest of LA (OR=1.4; 95% CI: 1.01-1.87). Conclusions: AAW in NO are more likely to have poorly differentiated and Tneg BC compared to AAW in the rest of LA. This disparity remains when comparing our data to previously published literature in other parts of the US. We plan to continue our data analysis and compare NO data to the national average as the HER2 data become available in the SEER Program to better characterize the disparity. This newly identified disparity in the AAW population in NO has clinical implications and translational research potential as it enables us to broaden the understanding and treatment of this aggressive disease.
Breast cancer and diabetes.
Authors: Autier Philippe , Koechlin Alice , Robertson Chris , Bota Maria , Boniol Mathieu , Leroith Derek , Bolli Geremia , Rosenstock Julio , Boyle Peter
Published: March 2020

e12507

Background: Diabetes and Breast Cancer are common conditions in women and there have been various links proposed between the two conditions. Methods: To clarify the potential association between diabetes, related factors, treatments and breast cancer risk, a series of meta-analyses were carried out following PRISMA guidelines. Results: For breast cancer at all ages, the risks obtained from prospective studies were: diabetes (SRR=1.27, 95% CI (1.16, 1.39); physical activity (SRR=0.88 (0.85, 0.92)); glycaemic load (SRR=1.05, (1.00, 1.10)); glycaemic index (SRR=1.05, (1.00, 1.09)); fasting glucose (SRR=1.14, (0.94, 1.37)); serum insulin (SRR=1.11, (0.75, 1.85)); c-peptide (SRR=1.00, (0.69, 1.46)) and adiponectin (SRR=1.16, (0.93, 1.46. An increase of 5 units in BMI was associated with post-menopausal breast cancer (SRR=1.12, 95% CI (1.08, 1.16)) but not at pre-menopausal ages (SRR=0.83, 95% CI (0.72, 0.95)). Serum insulin and c-peptide were associated with breast cancer at post-menopausal ages but not at pre-menopausal. For IGF-1, Hodge’s Standardised Mean Difference (HSMD) was calculated and there was no significant association with breast cancer (HSMD=0.026, 95% CI (-0.031, 0.084). The SRR for breast cancer among users of insulin glargine was 1.08 (0.98, 1.20) and was 0.92 (0.32, 2.65) when restricted to randomized trials. Among new users, the SRR for breast cancer was 1.09 (0.98, 1.21) and there was no trend of increasing breast cancer risk with increasing duration of use of glargine (β=0.04)(p=0.52). Risk of breast cancer in a prospective cohort declined with increasing follow-up, from 1.99 (1.31, 2.03) with two years of follow-up, to 1.60 (1.10, 2.32) with 3 years, 1.50 (1.10, 2.10) with four years and 1.18 (0.84, 1.66) with five years of follow-up. There is no reduction in risk of breast cancer associated with metformin use (SRR=0.96, 95% CI (0.85, 1.08)) even for the longest duration of use (SRR=0.94, 95% CI (0.81, 1.09)). Conclusions: An association between these two common diseases could have important implications for public health with common risk factors driving further increases in both diseases yet holding the tantalizing possibility for prevention of both. Overweight/Obesity and Physcal activity appear to be common links with the two diseases.
Race-based mortality as determined by intrinsic breast tumor subtype and p53 status.
Authors: Dookeran Keith A. , Dabbous Firas M , Booth Benjamin J
Published: March 2020

e12519

Background: Race-based mortality differences have been reported for intrinsic breast tumor subtypes. p53 status has recently emerged as a marker of worse prognosis among African-American (AA) women with breast cancer; however, the impact of p53 status on mortality by specific subtype is not clear. Methods: Multivariable (age, stage and race adjusted) stratified (subtype and p53) analyses with proportional hazards regression models [hazard ratios (HR), 95% confidence intervals (CIs)] for all-cause mortality, in a cohort of 331 AA and 203 non-AA women (115 Hispanic, 88 non-Hispanic white) of lower socioeconomic status, consecutively treated for breast cancer at an urban hospital, with 60.4 months median follow-up, and known intrinsic subtype and p53 immunohistochemical status. Results: The Table shows the effect of p53 status and demonstrates increased mortality hazards across all subtype strata for AA women compared to non-AA. The largest change in hazards was observed for luminal A and HER2 subtype tumors with higher stage, but this pattern was also evident for lower stage tumors. Hazards of death were least increased across basal type tumors. Conclusions: Across each level of subtype, p53+ status increased the hazards of death in AA women with breast cancer. However, mortality hazards appeared most increased in women with luminal A and HER2 type tumors. [Table: see text]
Diabetes, insulin resistance, and metabolic syndrome in women at high risk for breast cancer.
Authors: Dumais Valerie , Verma Shailendra , Fontaine-Bisson Benedicte , Lumingu Julienne , Paquet Lise
Published: March 2020

e12522

Background: Despite the growing body of research on diabetes (Db), insulin resistance (IR) and metabolic syndrome (MetS) in association with breast cancer, the prevalence of these metabolic conditions has yet to be explored in the high risk population. Delineating the numerous factors that contribute to these women’s risk is key in the management of this vulnerable population, especially when outlining potentially modifiable risk factors. The overall objective of this prospective study was to quantify the prevalence of Db, IR and MetS in women at high risk for breast cancer. Methods: Participants consisted of 100 Caucasian women above the age of 35 with an estimated 5yr risk of ≥1.7%. This criteria was met by (a) BRCA mutation carriers, (b) history of LCIS, (c) history of ADH, (d) history of mantle radiation, or (e) calculated 5yr risk of ≥1.7% using the Gail model. A comprehensive metabolic profile was obtained for each participant based on a questionnaire, fasting blood sample and biophysical measurements. The diagnostic criteria used for Db were those established by the Candian Practice Guidelines. The threshold for IR was a HOMA-IR value of 2.29. The MetS diagnostic criteria were those set by the IDF where 3 of 5 criteria from ↑waist circumference, ↑triglycerides, ↓HDL, HTN and hyperglycemia must be met. Results: The frequency (%) of Db (n=97), IR (n=96) and MetS (n=88) was 5(5), 17(18) and 29(33) respectively. Among the components of MetS, ↑waist circumference had the highest prevalence 60(68.2), followed by HTN 33(37.5), hyperglycemia 27(30.7), ↑triglycerides 23(26.1) and ↓HDL 22(29.7). There was a significant correlation observed between the Gail score and HDL (0.37, p<0.01), as well as systolic Bp (0.28, p<0.01). Conclusions: The prevalence of IR and MetS in this sample of women at high risk for breast cancer is considerably higher than the prevalence of these metabolic conditions in a similar population of average risk women, based on population data. This supports the significance and feasibility of an experimental study comparing the prevalence of IR and MetS in women at high risk and average risk for breast cancer. The prevalence of Db in this sample was comparable to the prevalence described in the general population.
Clinicopathologic characteristics of Lebanese patients under and over the age of 40 presenting with breast cancer at a single institution.
Authors: Shamseddine Ali , Abu Kar Sarah M , Alameddine Raafat , Saleh Ahmad , Temraz Sally , Mukherji Deborah , Majzoub Nadim , Dimassi Hani , Tfayli Arafat , Mahfouz Rami , Nemer Georges , Seoud Muhieddine A , El-hajj Ghada , Saghir Naji , Boulos Fouad
Published: March 2020

e12525

Background: The objective of this study was to determine the clinicopathologic characteristics of Lebanese patients with breast cancer below 40 compared to those above 40 presenting to our institution. Methods: Using a cross-sectional study design, data were collected prospectively on a sample of 110 women newly diagnosed with breast cancer. Comparison between the groups was performed using Person Chi-square and Fishers exact test. Results: 28 patients were ≤ 40 years and 82 patients >40 years. 75% and 76.5% of patients above and below 40 years respectively presented with stage I or II disease, more patients above 40 presented with stage I compared to those below 40 (32.4% vs 8% respectively). 50% of the younger age group presented with a grade 3 tumor; however, more than the half of the older group presented with grade 1 or 2. The older age group had a higher incidence of concurrent lobular and intraductal carcinoma (0 vs 6.4%). The younger age group was more likely to present with nodal involvement (57.1% vs. 48.45 for younger and older age groups respectively). Similar proportions of the two age groups stained positive for cyclin B1, p53, and VEGFR. All patients stained positive for PDGFR. Mean value of Ki-67 was 21.8% and 24%in younger and older age groups respectively. These differences were not statistically significant. Methylene Tetrahydrofolate Reductase (MTHFR) single nuccleotide polymorphism (SNP) T677T was detected in 21% of the older group compared to 5% of the younger population. Stratified to age Vitamin D receptor (VDR) SNP ApaI A/A was found in similar proportion in both groups (35% and 33.3% in younger and older group) while 30% and 41.3 % carried the vitamin D receptor (SNP) BSMI b/b in younger and older group respectively. Conclusions: No significant differences in the clinicopathologic characteristics examined between patients younger or older than 40 years were found in this sample. Analysis of a larger sample size including BRCA gene mutation analysis is planned to determine differences between age groups and possibly explain the higher incidence of breast cancer in the younger age group in our population.
Age disparities in the trend of colorectal cancer incidence in California.
Authors: Zell Jason A. , Singh Kathryn E. , Taylor Thomas H. , Pan Chuan-Ju G. , Stamos Michael J.
Published: March 2020

e12528

Background: Colorectal cancer (CRC) incidence has decreased over the past three decades, due in part to screening for pre-malignant polyps. Relatively little is known about CRC incidence among adults under age 50 (when screening recommendations commence for average-risk individuals). We examined CRC incidence trends with a focus on adults under age 50, in order to identify high-risk subgroups. Methods: 231,544 incident CRC cases (including 21,220 adults <50) from the California Cancer Registry from 1988-2009 were analyzed. We assessed age-specific incidence rates by race/ethnic group, gender, and tumor location within the colorectum, and calculated annual percent change (APC) to monitor change in incidence over the 21-year study period. Results: We observed increased CRC incidence rates in the adult population under age 50 in all examined race/ethnic groups, especially in Hispanic males (APC=+7.5%/p=0.0001) and Caucasian females (APC=+6.5%/p<0.0001). Young individuals were also more likely to present with metastatic disease at diagnosis. Overall, African Americans had the highest overall incidence rates and were most likely to present with metastatic disease compared to other groups. Conclusions: Incidence of CRC in adults under 50 is increasing across all race/ethnic groups. The high frequency of metastatic disease at initial presentation in this age group is particularly concerning. However, a considerable limitation of this analysis is the lack of data on family history of CRC. Our observations highlight the importance of identifying at-risk adults under age 50, especially those in higher-risk race/ethnic groups, with the overarching goal of decreasing the burden of CRC through screening and early detection.
Barriers for compliance to breast, colorectal, and cervical screening cancer test among Hispanics patients.
Authors: Ruiz Yelitza , Betancourt Elba , Miranda Christine , Hunter Robert F.
Published: March 2020

e12544

Background: Hispanics are less likely to undergo colorectal cancer and cervical cancer screening tests than non-Hispanic population. We address the barriers for compliance in a Hispanic community. Methods: A descriptive study was performed with 194 patients between 21 to 85 y/o, while they attended routine medical encounters at a private and a government sponsored clinics. Compliance and barriers for non compliance for mammography (MAMMO), occult blood testing (FOBT), colonoscopy (COLO) and cervical smears (Pap) were studied. Univariate and bivariate tests were used. Results: Females (62.9%) had a mean age of 53.4 ±15.0; had a high school diploma or higher degree (80.5%), unemployed (52.15), had private health insurance (68.0%), and practiced routine medical checkups (79.9%). Gender differences for patients undergoing FOBT and COLO were found only in patients older than 50 y/o. Females were more likely than males to undergo COLO (62.3% vs. 42.2%; p<0.05) whereas males are more likely than females to had a FOBT (66.7% vs. 56.5%; p>0.05). Differences between employed and unemployed patients undergoing FOBT were seen (48.4% vs. 65.1%; p=0.105) and COLO (38.7% vs. 60.2%; p=0.040). Seventy four percent of women between 40 to 65 y/o had a Pap and 85% had a MAMMO. Predominant reasons for avoiding MAMMO and Pap were fear (20%; p<0.05 and 6%; p>0.05), uncomfortable sensation (13%; p<0.05 and 19%; p<0.05), lack of time (67%; p<0.0001 and 56%; p<0.0001). Reasons for avoiding FOBT and COLO were not recommended by physician (42%; p<0.05 and 52%; p>0.05) and lack of knowledge (16%; p<0.05 and 17%; p<0.05). Conclusions: Occupational status in women (p<0.05) was found as a barrier for compliance with screening MAMMO, while it was also a barrier for COLO in both men and female over the age of 50. (p<0.05) Educational level in men and women was not associated with non compliance with FOBT or COLO in patients older than 50 y/o. Having a private health insurance is a predictor of compliance with MAMMO (71.3%), FOBT (78.3%), COLO (80.6%), and Pap (68.6%). Several physician and patient related factors were identified as barriers for compliance. Study was supported by NIH grant #'s 8U54MD007587 & 8G12MD007583.
Presence of familial colorectal cancer type X in families fulfilling Amsterdam criteria for Lynch syndrome in southern Brazil.
Authors: Ashton-Prolla Patricia , Schneider Naye Balzan , Netto Cristina , Cossio Silvia Liliana , Koehler-Santos Patricia , Meurer Luise , Prolla Joao Carlos
Published: March 2020

e12546

Background: The clinical diagnosis of Lynch syndrome is usually established when a family fulfills the Amsterdam Criteria, and confirmed by identification of MMR deficiency and/or germline mutations in one of the MMR genes. In a subset of families with Amsterdam criteria, no evidence of DNA mismatch repair deficiency can be identified and this clinical entity has been designated “Familial Colorectal Cancer Type X (FCCTX)”. Methods: The prevalence of MMR deficiency was assessed in a group of 25 individuals with colorectal or endometrial cancer from 20 families fulfilling Amsterdam criteria in Southern Brazil. MMR deficiency was assessed by IHC testing using a panel of antibodies against MSH2, MLH1, MSH6, and PMS2. In cases showing loss of nuclear expression of MLH1, presence of the BRAF p.V600E mutation and microsatellite instability were assessed in the tumor. Results: Fourteen of the 20 families studied fulfilled Amsterdam II criteria. MMR deficiency was identified in the tumor of 11 index cases and in the remaining 9, nuclear expression of all four MMR proteins was normal, suggesting the diagnosis of FCCTX. This FCCTX phenotype was observed in both Amsterdam I and Amsterdam II families. CRC with MMR-deficiency was diagnosed at an earlier age (41.2 years) than CRC showing MMR proficiency (47.2 years), although the difference did not reach significance. Conclusions: FCCTX is a frequent differential diagnosis in hereditary colorectal cancer in patients presenting to high risk cancer genetics clinics in Southern Brazil and further molecular characterization of hereditary colorectal cancer families with these features is warranted.
Meta-analysis of sweetened carbonated beverage consumption and cancer risk.
Authors: Koechlin Alice , Autier Philippe , Boyle Peter
Published: March 2020

e12548

Background: There is speculation of possible links between sweetened carbonated beverage consumption and the risk of developing cancer. The aim of this study was to examine the association between sweetened, carbonated beverage consumption and cancer risk. Methods: PRISMA guidelines of meta-analyses were followed as closely as possible. Over 50 independent estimates of risk were available, 11 for colas specifically. A random effects meta-analysis was performed with tests for publication bias (Begg, Egger, Macaskill) performed as well as Higgins and Thompson’s I2 measure of the percentage of heterogeneity between studies which could not be explained by chance. Results: Overall the different sites of cancer, the summary relative risk (SRR) when all 56 independent estimates were considered together was SRR=1.04 (95% CI (0.96, 1.13)). On this overall scale, there appears to be no association between consumption of soft-drinks and the risk of cancer. When individual cancer sites were considered, there was no significant increase, or decrease in the meta-analysis estimate of risk of cancer of the pancreas, bladder, kidney, oesophageal squamous cell or adenocarcinoma, colon, gastric cardia, gastric non-cardia, prostate, breast, larynx and ovary nor from the oral cavity, pharynx, glioma, leukaemia or non-Hodgkin’s lymphoma where only one study was available. There was no evidence in a sensitivity analysis from those studies which reported results separately for coke, pepsi or other colas of an associated risk of pancreas cancer (SRR=1.00, 95% CI (0.61; 1.65)) based on three studies. The results for all other forms of cancers were greatly hampered by poor methodology and small numbers of studies (mainly one report on each cancer site studied). Conclusions: Overall, the findings are reassuring regarding the association between soft drinks, including colas and cancer risk, although the quality of many of the studies is quite poor by acceptable, modern standards and no study has been conducted with use of carbonated beverages as a primary hypothesis.
Variations in breast cancer awareness among urban Tanzanian women.
Authors: Morse Emma Perry , Maegga Bertha , Joseph Getrud , Miesfeldt Susan
Published: March 2020

e12561

Background: Nearly 70% of the 7.6 million cancer deaths occur annually in developing countries like Tanzania, with breast cancer being among the most common causes of cancer mortality. Although data are incomplete, late-stage disease is believed to limit breast cancer control in Tanzania, with delayed diagnosis linked to low levels of breast cancer awareness among women. The goal of this study was to explore awareness of this disease among low-income women accessing routine medical care from three district hospitals in Dar es Salaam, Tanzania. Methods: This survey-based study examined participants' knowledge, attitudes, and beliefs regarding breast cancer causes, risk factors, symptoms, early detection measures, treatment, and preferred education sources. Sociodemographic variations in knowledge of breast cancer risk factors, symptoms, and treatments were assessed. Results: Two hundred and twenty-five women, ages 18-55 years, participated. Over half (52%) reported a primary school education or less; 69.9% were married; 26.2% were unemployed. The average monthly household income was just below the Dar es Salaam mean. Ninety-eight percent were aware of breast cancer; 22% knew someone with a history of breast cancer. Among the 126 women who heard of breast self exam, 25% and 34% practiced it regularly and occasionally, respectively; 41% never practiced it. Only 6.2% had regular clinical breast exams. A minority knew of mammography (32%); <2% had undergone a mammogram. Of the items listed, respondents correctly identified symptoms (51%), risk factors (31%), and treatments (51%). Data reflecting sociodemographic variations in knowledge will be shown. Preferred sources of breast cancer educational materials included group sessions, television or radio programs, and meetings with breast cancer survivors. Conclusions: This work provides valuable insight into preferred sources of breast cancer education among Tanzanian women.
Gastrointestinal cancer risk in Irish hereditary breast ovarian cancer families.
Authors: Lyons Tomas G , Gogarty Darragh S , Farrell Michael P. , Dorman Naoise Maria , Green Andrew J , Gallagher David J.
Published: March 2020

e12565

Background: Colorectal and breast cancer are linked in certain predisposition syndromes such as Cowden and Peutz-Jegers syndrome. Breast cancer risk also appears increased in certain Lynch Syndrome kindreds. Original reports suggested an increased risk of gastrointestinal malignancies in BRCA1 or 2 mutation carriers. Two large studies in Ashkenazi Jewish populations subsequently contradicted this evidence, although only the three founder mutations were included in these studies. We report the Irish experience of colorectal and gastro-oesophageal (GE) cancer in Irish hereditary breast ovarian cancer (HBOC) families. Methods: 104 HBOC families at two tertiary referral centres were reviewed for the presence of early onset gastrointestinal (GI) malignancies. The medical records of individuals with GI cancer were reviewed to determine carrier status. Clinical data including age at diagnosis, stage, treatment and outcome were extracted. Median age of diagnosis and outcome were compared among BRCA1/2 mutation carriers and non-carriers. Results: We identified 33 individuals with GI malignancies in 102 HBOC families (22 with colorectal, 11 with gastric). Definitive carrier status was available on 8 individuals. An additional 7 individuals were obligate carriers. Age at diagnosis ranged from 27-84 years (median=60). Median age of colorectal cancer diagnosis among carriers was 54 compared with 61 among non-carriers. Median age of gastric cancer diagnosis among carriers was 66 compared with 53 among non-carriers. Conclusions: Early onset colorectal cancer occurs in certain HBOC families and may be related to mutation status. No genotype-phenotype association was identified in this study. An additional 60 Irish HBOC families are being screened for GI malignancies and updated data will be presented at the meeting.
The prevalence of abnormal cervical cytology among postnatal clinic attendees at the University of Calabar Teaching Hospital, Calabar, Nigeria.
Authors: Ago Boniface Uji
Published: March 2020

e12568

Background: Carcinoma of the uterine cervix is a deadly but preventable disease. It is still a major gynecologic problem in our subregion. Cervical cytology remains the key to its early detection and prompt treatment. Methods: This was a prospective cross sectional study of postnatal women to determine the prevalence of abnormal cervical cytology and their socio-demographic characteristics. Institutional ethical clearance and informed consent of participants were obtained. Aye's spatula and endocervical brush were used to collect specimen from the ectocervix and endocervix respectively and smeared on individually labelled glass slides. The samples were treated using the conventional Papanicolaou staining method and reported using the Bethesda system. Researcher-administered questionnaire generated data as well as results of cytology were analyzed using Epi-Info version 3.5.1.0 (CDC Atlanta USA 2008). Results: There were 100 women screened. Three percent had low grade squamous intraepithelial lesion. Colposcopy done, however, did not reveal abnormal findings. Ninety-five percent of the women had no prior knowledge of cervical cancer and Pap smear. Two percent of the women had a family history of cervical cancer and both patients died of the disease due to lack of facilities for treatment. Conclusions: Cervical cancer is a preventable disease. Women in our subregion are under-screened. Effective screening methods are the mainstay in its prevention. Availability of well equipped gynecologic oncology centers with personnel training are a necessary end to this carnage.
Management of breast cancer associated with pregnancy.
Authors: Lewis Catherine Renee , Robertson Alysia , Yan Fengxia , Danner Omar , Beech Derrick
Published: March 2020

e12573

Background: Pregnancy-associated breast cancer (PABC) continues to be a challenging problem and may be increasing in frequency as women delay childbearing. As of yet, there is no absolute consensus on the management of PABC. Methods: In order to determine the ideal management for breast cancer during pregnancy, a comprehensive chart review of all women diagnosed with breast cancer during pregnancy from 1995-2010, at a large, urban hospital was performed. We reviewed the medical records of over 2000 patients and identified 15 individuals with PABC. A literature review and retrospective analysis of treatment modalities used for patients diagnosed with breast cancer during pregnancy or during the immediate postpartum period were performed. Trimester of pregnancy, stage at diagnosis, nodal status and age were compared amongst pregnant and non-pregnant patients. The study was approved by our institutional review board. Results: Preliminary results indicated that there was an even distribution between stages of breast cancer at diagnosis among our patient population. Over 80% of the patients had infiltrating ductal carcinoma. Of the patients diagnosed during the first or second trimester, the majority underwent breast conservation therapy (BCT) with subsequent chemotherapy and/or radiation after delivery. Several patients underwent elected to terminate their pregnancy and received chemotherapy either during pregnancy or after termination. Conclusions: Our analysis shows that BCT is the most common treatment strategy for PABC at our institution, which is consistent with current literature. BCT appears to be safe and well tolerated in patients with PABC. Infiltrating ductal breast cancer is the most common type of malignancy in this subpopulation. A multi-disciplinary approach involving obstetricians, medical oncologists, radiation oncologists and surgical oncologists is needed to provide optimal care to these patients.
Bevacizumab (BV) plus irinotecan (I) in recurrent glioblastoma multiforme (GBM): A single center experience.
Authors: Iruarrizaga Eluska , Azkona Eider , Aresti Unai , Rubio Itziar , Arruti Mikel , Carrera Sergio , Fuente Natalia , Marrodan Ines , Lopez Escola Cristina , Condori Elizabeth , Mane Joan Manel , Lopez-Vivanco Guillermo
Published: March 2020

e13000

Background: Glioblastoma multiforme constitutes the most common and malignant form of primary brain tumor. Median survival for recurrent disease is 3-9 months. Combining bevacizumab with irinotecan represents an option of treatment in recurrent GBM. Methods: We performed a retrospective review of patients with recurrent GBM treated with bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 for patients receiving enzyme-inducing antiepileptic drugs –EIAEDs- and 125 mg/m2 for patients not receiving EIAEDs) every 14 days on a 4-week cycle. Inclusion criteria: age ≥ 18, histology of GBM, progression after radiotherapy and temozolomide and signed informed consent for bevacizumab compassionate use. MRI-FLAIR sequence was used every 8 weeks to assess response. Results: From October 2009 to December 2012, a total of 26 patients were included; 15 (57.7%) male/11 (42.3%) female. Median age of the patients was 52 years (32-69); ECOG 0/1/2/3: 7.7/46.2/38.5/7.7% respectively; 19.23 % of patients received EIAEDs. Median number of cycles was 2.5 (1-14). Response rate was 30.8% (23.1% PR; 7.7 % CR); SD 23.1 %. Median PFS was 23 weeks; median OS was 30 weeks. Most common grade 3 toxicities were: asthenia 26.9%, arthromyalgia 3.8%, diarrhea 3.8% and hepatotoxicity 15.4%; grade 2 thromboembolic complications: 3.8 %. Conclusions: Combination of bevacizumab and irinotecan is effective against recurrent GBM and prolongs PFS and OS compared with historical controls, with mild toxicity.
Continuation of adjuvant temozolomide until tumor progression after upfront chemoradiation therapy produces promising survival in patients with GBM, especially with pseudoprogression.
Authors: Gahramanov Seymur , Tyson Rose Marie , Lacy Cynthia , Prola Netto Joao , Nasseri Morad , Fu Rochelle , Giles Stephen , White Tricia , Neuwelt Edward A.
Published: March 2020

e13001

Background: Radiation therapy with concomitant temozolomide (TMZ) followed by 6 months of adjuvant TMZ is standard of care in newly diagnosed glioblastoma multiforme (GBM). The 6-month time frame for adjuvant TMZ was chosen arbitrarily and the optimal duration of TMZ chemotherapy remains undefined. In addition, the duration of TMZ chemotherapy and survival can be affected by uncertainty in differentiating pseudoprogression (Ps), indicating necrosis/inflammation, from true tumor progression. This IRB-approved retrospective study determined the survival of GBM patients treated with chemoradiotherapy (CRT) and adjuvant TMZ continued until tumor progression. Methods: Patients with biopsy-proven newly diagnosed GBM at Oregon Health and Science University from January 2006 to June 2012 were treated with upfront CRT followed by adjuvant TMZ without Pneumocystis jirovecii pneumonia prophylaxis until tumor progression. Diagnosis of Ps was made by relative cerebral blood volume (rCBV) estimation based on perfusion MRI with ferumoxytol or RANO criteria. Survival was determined using Kaplan-Meier product limit analysis. Results: A total of 67 patients were included. Overall median survival in the whole group was 21.3 months (95% CI 17.3, 26.3), significantly higher than the median survival in Stupp et al (2008) (14.6 months; 95% CI 13.2, 16.8). However 46 (69%) patients of our series received bevacizumab. Ps was diagnosed in 17 of 47 patients underwent ferumoxytol perfusion MRI based on rCBV measurement; 4 additional Ps cases were diagnosed based on RANO criteria. Median survival in the 21 patients with Ps was 49.1 months, though the estimate may be unstable due to the small sample size and 12 patients remain alive. Median TMZ cumulative dose for all patients was 5250 mg/m2 (range 2250 to 64000). Conclusions: The increase in median survival compared to historical data supports the continuation of adjuvant TMZ treatment, especially in patients with Ps. Differentiation between true tumor progression and Ps is important for treatment (TMZ) decisions and may affect survival. Ferumoxytol perfusion MRI may help as diagnostic tool.
Imatinib plus hydroxyurea in pretreated nonprogressive glioblastoma (GBM): Long-term follow up of a single-center phase II study.
Authors: Dresemann Gregor Paul
Published: March 2020

e13004

Background: GBM is malignant brain tumour with a median survival of 15.6 months. Dysregulated signalling of platelet derived growth factor receptors is suggested to play a role in pathogenesis. The combination of imatinib (I) plus hydroxyurea (HU) is known to be well tolerated and to show moderate efficacy in patients (pts) with recurrent GBM. Despite the aggressive course of GBM once starting progression, short periods of disease stabilisation after primary treatment or effective treatment of relapse can be observed. This Phase II study was initiated to analyse the efficacy of I plus HU as maintenance treatment (MT) in GBM pts. Methods: From December 2003 up to June 2005 30 pts were included. No enzyme-inducing anticonvulsive drugs were allowed. I (600 mg/day) and HU (1000 mg/day) were given as a continuous treatment. Blood cell counts were taken weekly and magnetic resonance imaging every 6 weeks. Primary endpoint (PE) was 6 and 12 months progression free survival (PFS), secondary endpoints (SE) were 5 years PFS and overall survival (OS). Results: All pts were eligible for PE and SE. 25 pts were male, 5 pts female, median age was 44 years (32 to 71). All pts had prior irradiation, 21 pts had prior temozolomide (T) containing therapy and 9 pts non-temozolomide containing therapy. 8 pts had none, 17 pts one and 5 pts two prior relapses. 25 pts had measurable disease, 4 of these pts achieved a partial response (PR), there was no complete remission, 5 pts had no evidence of disease. Median follow up is 90 months. Hematotoxicity grade 2 and 3 occurred in 11 out of 30 pts and required dose reduction of HU in 8 pts, dose reduction of I in 1 patient and G-CSF in 8 pts. PFS rate at 6, 12, 24 and 60 months were 60% (18/30), 40% (12/30), 17% (5/30) and 17% (5/30 ) respectively, OS rate at 6, 12, 24 and 60 months were 90% (27/30), 67% (20/30), 37% (11/30) and 17% (5/30). 4 pts are still alive without progression. Conclusions: Although I and HU did not demonstrate relevant efficacy in GBM and never reached admission status the reported study indicates impressive long-term survival data for I and HU as a continuous oral MT. Further studies should analyse more effective drugs like temozolomide as MT (proof of principle). Clinical trial information: STI571DE21.
High expression levels of CD90 to predict edema response to steroid treatment in glioblastoma multiforme (GBM) patients.
Authors: Belda-Iniesta Cristobal , Holgado Esther , Hitt Ricardo , Prat Ricardo , De Castro Javier , Ibañez de Cáceres Inmaculada , Perona Rosario , Ayuso Sacido Angel
Published: March 2020

e13008

Background: GBM is the most aggressive brain tumour in the adult, with a median overall survival about 15 months. Patients usually present with many symptoms due to edema in addition of symptoms derived from the increasing tumour mass. Edema- dependent symptoms are currently treated with steroids. However, a number of patients do not respond to this therapy and almost all develop severe adverse effects. Currently, there is no biomarker that allows neuro-oncologists to predict edema response to steroid therapy. Methods: This is an observational study aimed to identify molecular markers based on massive expression analysis to predict edema response to steroids in patients diagnosed with GBM. Patients received dexamethasone (4mg bid) before surgery when high-grade glioma was suspected in contrast-enhanced brain MRI. 7 days later a second brain MRI was performed just before surgery to evaluate edema response according with RANO criteria. We collected neurological examinations at days -7 and -1 before surgery, surgical morbidity and time- to- recovery. Expression patterns (proliferative vs. mesenchymal) and a library of molecular markers related to both glioma-initiating cells and more differentiated cells from tumour mass were explored in tumoral and matched control samples from this cohort. Finally, we compared the expression levels of the selected molecular markers together with edema- responses after steroid therapy measured by brain MRI as well as with clinical values. Results: We recruited 54 patients and observed 32 edema- responses. We found that CD90 expression levels similar or above controls correlates with MRI response to steroids. Symptoms improvement and GBM resection without clinical worsening (p = 0.016). Nonetheless, we did not observed any association between CD90 expression level below controls and lack of response. Interestingly, we have observed that steroid responsiveness is not related with the proliferative and mesenchymal nature of the tumour. Conclusions: CD90 expression is a good predictor of edema response to dexamethasone and may be useful to identify candidates for steroid therapy.
The role of Rac proteins in glioblastoma stem cells.
Authors: Lai Yun-Ju , Yu Jei-Hwa , McFarland Braden C , Benveniste Etty N
Published: March 2020

e13011

Background: Glioblastoma is the grade 4 astrocytoma which is notorious for its highly invasive phenotype, very low survival rate and generally poor responses to conventional therapies. Glioblastoma stem-like cells (GSC), which are usually more resistant to therapeutic treatment, may account for the poor prognosis of this disease. Rac (Ras-related C3 botulinum toxin substrate) is a subfamily of Rho small GTPase which function is regulation of actin cytoskeleton rearrangement. While Rac1 is expressed ubiquitous in different tissues and cells, Rac2 is highly expressed in the mesenchymal subtype of glioblastoma according to the TCGA (the Cancer Genome Atlas) database, and Rac3 is mainly expressed in the brain. Methods: We used Rac proteins overexpressing-glioblastoma cellines derived GSC and Rac proteins specific siRNA harboring-GSC to perform colony formation assay and migration assay. Results: Here we report that Rac proteins overexpressing glioblastoma stem-like cells derived from glioblastoma cell lines have higher proliferation rate and stronger responses to LPA-induced cell migration. Knocking-down their expression by specific siRNA reduces the proliferation and migration of these cells. Instead of Rac1, Rac2 and Rac3 are more effective on promoting proliferation and migration of glioblastoma stem-like cells. Moreover, Rac proteins promote glioblastoma progression is associated with activation of JAK-STAT and ERK pathway. Conclusions: Although Rac1 is the most studied one in the Rac family, and has also been implicated in the progression of different cancers, however, it is homogeneously expressed in all different tissues, and plays important roles in normal cellular functions involving cell movement, such as wound healing, make it not a good candidate for specific drug targeting. According to our results, Rac2 or Rac3 serve as a better potential therapeutic targets for glioblastoma treatment.
Metastatic ACTH-producing pituitary carcinoma managed with combination pasireotide and bevacizumab following failure of temozolamide therapy: A case report.
Authors: O'Riordan Lynda M. , Greally Megan , Coleman Niamh , Breathnach Oscar S. , Hennessy Bryan , Thompson Christopher J , Grogan William
Published: March 2020

e13022

Background: ACTH-producing pituitary carcinomas (APPC) are malignant neuroendocrine tumors affecting the adenohypophysis. They are extremely rare, with a poor prognosis. They are poorly responsive to chemotherapy and radiotherapy. We report the case of a 25 year old female with a diagnosis of APPC, metastatic to bone, treated with temozolamide, followed by bevacizumab and the novel agent, pasireotide. Methods: The patient was diagnosed in 2002 with an ACTH-secreting pituitary macroadenoma causing Cushing’s disease. Despite two transphenoidal surgeries, bilateral adrenalectomies, craniotomy with excision of pituitary fossa tumour and radiotherapy she developed aggressive Nelson’s Syndrome. Following discontinuation of a somatostatin analogue in 2009 her ACTH levels rose dramatically causing progressive skin hyperpigmentation. Her disease continued to progress despite CyberKnife treatment. She was referred for temozolamide chemotherapy for treatment of the pituitary adenoma. At review, she had severe back pain. Investigations suggested metastatic disease and biopsy confirmed a diagnosis of metastatic APPC to bone.We commenced treatment with Temozolamide, however her disease progressed – ACTH levels were >200,000pmol/l in June 2012. Molecular profiling completed on the patient’s tissue was negative. Pasireotide, a novel multi-somatostatin receptor analogue, was commenced concomitantly with the anti-angiogenesis agent bevacizumab. Results: Treatment response is being assessed with imaging, serial monitoring of serum ACTH levels and skin examination. Interval imaging has shown stable disease, ACTH levels have decreased to 113,000pg/ml. Conclusions: Pituitary carcinomas are extremely rare representing 0.1-0.2% of pituitary neoplasms. To date, there is no established standard treatment, although there are reports of response to temozolamide.Our patient exhibited a clinical improvement and a reduction in ACTH levels after 6 months of combination therapy with pasireotide and bevacizumab. This combination is a possible therapeutic option in patients with metastatic ACTH-producing pituitary carcinoma.
Outcome of an advanced anaplastic astrocytoma patient treated with Newcastle disease viral (NDV) oncolytic therapy.
Authors: Freeman Arnold , Bakacs Tibor , Moss Ralph W
Published: March 2020

e13029

Background: Oncolytic viruses are increasingly recognized for their potential promise of lasting impact on our cancer treatment repertoire. The use of attenuated Newcastle Disease Virus (NDV) against cancer was pioneered more than 40 years ago by Laszlo Csatary, a Virginia physician, who died March 20, 2012 at age 88. In 1968, Csatary used attenuated NDV as a cancer treatment. NDV, an RNA virus, shows tumor selectivity in its replication behavior in mammalian cells, including humans. Methods: A.G., a 14-year-old boy, presented in September 1994 with a large left fronto-temporal mass. The tumor was debulked and he then received 56 Gy of radiation to the brain. Pathology indicated the tumor was a glioblastoma multiforme (GBM). By November1995 there was local recurrence. Despite various chemotherapies, the cancer progressed. In May 1996 patient started on attenuated intravenous NDV in Budapest, Hungary. This was the only agent he received for the next 8 years. Results: There was progressive shrinkage of the GBM resulting in complete disappearance at 1 year. The patient remains well with no evidence of tumor 16 years after the start of NDV. Conclusions: NDV was able to eradicate GBM in this seemingly hopeless situation and merits further evaluation in this and other cancers.
Temozolomide plus interferon-β for recurrent malignant glioma patients: Experience of 28 cases.
Authors: Chen Zhong-ping , Yang Qun-ying , Guo Cheng-cheng
Published: March 2020

e13037

Background: Previous studies showed that interferon-β may enhance chemosensitivity of temozolomide (TMZ) and nitrosoureas. The present study was to evaluate the efficiency and side effects of TMZ plus INF-β in recurrent malignant glioma patients. Methods: Patients (age≥18 years) with grade III-IV glioma that was progressive or recurrent after prior standard radiotherapy plus TMZ chemotherapy were eligible for the study. Patients were scheduled to receive INF-β 3MU subcutaneous injections on days 1, 3 and 5, while TMZ 200mg/m2orally on days 2 to 6, of a 4-week cycle until tumor progression or unacceptable toxicity. Tumor response was assessed by MRI every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) by Response Assessment in Neuro-Oncology Working Group (RANO) criterion. Secondary end points included progression free survival (PFS), overall survival (OS), and toxicity. Results: From July of 2010 to October of 2012, 28 patients were assessed (16 GBM and 12 grade III glioma). There were 22 males and 6 females, and the median age was 44.5 years (ranged from 22 to 73). The median KPS was 80 (70`100). Radiographic responses were noticed in 35.7% (10 of 28) of patients. There was none CR, but 10 PR, 14 stable disease (SD) and 4 progressive disease (PD). The median PFS was 6.0 months (95% CI 3.9-8.0),the median OS was not availability. The most common toxicities include grade±-2 neutropenia(4 cases), thrombocytopenia (3 cases), nausea and vomiting (3 case), fatigue (8 cases) and liver malfunction (3 cases). Grade III or ‡W toxicities were uncommon. Conclusions: Temozolomide plus INF-β has moderate efficacy for recurrent high grade glioma with acceptable toxicity, and thus worth further investigation.