Association between MDR1 polymorphisms and XELIRI and XELOX chemoresistance in Saudi patients with colorectal cancer.

Multidrug resistance member 1 (MDR1) is located on chromosome 7 and encodes P-glycoprotein, which is universally accepted as a drug resistance biomarker. MDR1 polymorphisms can alter protein expression or function, which has been previously reported to associate with various types of malignancies, such as colorectal cancer (CRC). Therefore, the present study aimed to determine the effects of MDR1 polymorphisms on drug responses of Saudi patients with CRC. DNA samples were obtained from 62 patients with CRC and 100 healthy controls. Genotypes and allele frequencies of MDR1 single nucleotide polymorphisms (SNPs) G2677T and T1236C were determined using the PCR-restriction fragment length polymorphism procedure. The results showed no significant differences in the genotype distribution and allele frequency of T1236C between patients with CRC and controls. However, G2677T was found to serve a highly significant role in protecting against the progression of CRC. In addition, none of the genotypes in SNPs T1236C and G2677T was found to affect chemoresistance to XELIRI and XELOX. In conclusion, although T1236C in the MDR1 gene is not associated with CRC risk, G2677T protects against the development of CRC. Neither of the MDR1 SNPs tested were associated with the risk of chemoresistance. Therefore, these two SNPs cannot be used as molecular markers for predicting drug response in patients with CRC.

Circulating miR-26a, miR-106b, miR-107 and miR-133b stratify hepatocellular carcinoma patients according to their response to transarterial chemoembolization.

BACKGROUND: A number of hepatocellular carcinoma (HCC) patients have developed resistance against transcatheter arterial chemoembolization (TACE) treatment. In this study, we aimed to develop a panel of microRNAs (miRs) biomarkers to predict clinical outcomes in HCC patients after TACE treatment. METHODS: The expression level of twenty miRs was evaluated in FFPE tissues collected from 33 HCC patients. We selected four differentially expressed miRs in TACE-responders versus non-responders and re-assessed their expression in 51 serum samples. The expressions of miRs associated with overall survival (OS), progression-free survival (PFS), and treatment outcomes were investigated. The diagnostic accuracy of these miRs in predicting patients' response to TACE was also evaluated. RESULTS: The baseline of miR-106b, miR-107 and miR-133b was significantly elevated (p < .001) in sera of TACE-responders while miR-26a was elevated (p < .001) in non-responders. miR-26a and miR-133b recorded the highest diagnostic performance as individual classifiers in response to TACE (AUC = 1.0 and 100% sensitivity and specificity). Intriguingly, miR-133b distinguished complete responders from partial responders and non-responders (AUC ≥ 0.90). The PFS was improved (p < .05) in the high expression group of miR-31, miR-200b, miR-133b and miR-181a over their low expression group. CONCLUSION: Circulating miR-133b, miR-26a, miR-107 and miR-106 in serum are potential candidates to be utilized as prognostic biomarkers for predication of TACE treatment outcomes in HCC patients.

First-line paclitaxel and cisplatin used sequentially or in combination in metastatic breast cancer: A phase II randomized study.

INTRODUCTION: Breast cancer (BC) is the commonest cancer among females worldwide. Some patients present initially at advanced stages and more than 50% of them will develop metastasis (MBC) at some point. Compared to single agents, combination chemotherapy produces higher response rates (RR), longer progression-free survival (PFS) than single agents. This is associated with remarkably higher toxicities. At the same time, overall survival (OS) is comparable. This study aimed to compare safety and efficacy of combination and sequential chemotherapy. PATIENTS AND METHODS: Forty-six MBC patients were randomized to receive 6 cycles of the combination of paclitaxel (175 mg/m2) and cisplatin (70 mg/m2) (combination PC) or paclitaxel for 3 cycles followed by cisplatin for 3 cycles (sequential PC). Endpoints were RR, PFS, OS and safety. RESULTS: Both combination and sequential PC produced similar RR (52% in both arms) and disease control rates (78.3% vs. 73.9%, p = .652). Responses were faster in the combination arm. Median PFS was 8.2 months in the combination compared to 5.0 months in the sequential arm (p = .064). The median OS was 16.5 and 18.8 months in the combination and sequential arms, respectively (p = .866). The combination was more toxic than sequential PC. Grade 3 toxicities were higher with combination PC than to sequential PC (48% vs. 4.3%; p < .001). CONCLUSION: Sequential agent chemotherapy may provide similar response rate and overall survival to combination chemotherapy with much lower toxicities. The former can be considered the standard practice in most instances.

The Egyptian clinical trials' registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov).

Registering clinical trials (CTs) in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP), the continental Pan-African CT Registry (PACTR) and the US clinicaltrials.gov (CTGR). In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage) was 686 (0.30%) in ICTRP, 56 (11.3%) in PACTR and 548 (0.34%) in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials) represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended.

Treatment Outcomes of Epithelial Ovarian Cancers Following Maximum Cytoreduction and Adjuvant Paclitaxel-Carboplatin Chemotherapy: Egyptian NCI Experience.

BACKGROUND: Epithelial ovarian cancer (EOC) is the commonest malignancy involving the ovaries. Maximum surgical cytoreduction (MCR) followed by adjuvant taxane-platinum chemotherapy are the standard of care treatments. AIMS: To study treatment outcomes of EOC patients that were maximally cyto-reduced and received adjuvant paclitaxel-carboplatin (PC) chemotherapy. MATERIALS AND METHODS: This retrospective cohort study included 174 patients with EOC treated at the Egyptian National Cancer Institute between 2006 and 2010. For inclusion, they should have had undergone MCR with no-gross residual followed by adjuvant PC chemotherapy. MCR was total abdominal hysterectomy/bilateral salpingo-oophorectomy [TAH/BSO] or unilateral salpingo- oophorectomy [USO] plus comprehensive staging. RESULTS: The median age was 50 years. Most patients were married (97.1%), had offspring (92.5%), were postmenopausal (53.4%), presented with abdominal/pelvic pain and swelling (93.7%), had tumors involving both ovaries (45.4%) without extra-ovarian extension i.e. stage I (55.2%) of serous histology (79.9%) and grade II (87.4%). TAH/BSO was performed in 97.7% of cases. A total of 1,014 PC chemotherapy cycles were administered and were generally tolerable with 93.7% completing 6 cycles. Alopecia and numbness were the commonest adverse events. The median follow up period was 42 months. The 2-year rates for disease free survival (DFS) and overall survival (OS) were 70.7% and 94.8%, respectively. The respective 5-year rates were 52.6% and 81.3%. Advanced stage and high-grade were significantly associated with poor DFS and OS (p<0.001). Age >65 years was associated with poor OS (p =0.008). Using Cox-regression, stage was independent predictor of poor DFS and OS. Age was an independent predictor of poor OS.

Investigating the pretreatment miRNA expression patterns of advanced hepatocellular carcinoma patients in association with response to TACE treatment.

Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents-doxorubicin and cisplatin-is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer.

Protumorigenic role of Timeless in hepatocellular carcinoma.

The mammalian timeless (TIM) protein interacts with proteins of the endogenous clock and essentially contributes to the circadian rhythm. In addition, TIM is involved in maintenance of chromosome integrity, growth control and development. Thus, we hypothesized that TIM may exert a potential protumorigenic function in human hepatocarcinogenesis. TIM was overexpressed in a subset of human HCCs both at the mRNA and the protein level. siRNA-mediated knockdown of TIM reduced cell viability due to the induction of apoptosis and G2 arrest. The latter was mediated via CHEK2 phosphorylation. In addition, siRNA-treated cells showed a significantly reduced migratory capacity and reduced expression levels of various proteins. Mechanistically, TIM directly interacts with the eukaryotic elongation factor 1A2 (EEF1A2), which binds to actin filaments to promote tumor cell migration. siRNA-mediated knockdown of TIM reduced EEF1A2 protein levels thereby affecting ribosomal protein biosynthesis. Thus, overexpression of TIM exerts oncogenic function in human HCCs, which is mediated via CHEK2 and EEF1A2.

Qatar biomedical and cancer publications in PubMed between 2000 and 2012.

BACKGROUND: The aim of this work was to analyse the past trends of biomedical and cancer publications from Qatar listed on PubMed for the years 2000-2012. These findings were then compared with the corresponding global number of publications. METHODS: PubMed was searched for cancer publications, clinical trials, publications on humans or other species. Searching for "Qatar*" in the "Affiliation" field yielded the lowest number of publications; searching for "Qatar*" in the "Affiliation" or in "Title/Abstract" yielded a moderate number of results and searching for "Qatar*" in the "Affiliation" or "Title/Abstract" or "Text Word" fields yielded the highest number of publications. The annual percentage change (APC) from one year to the next was calculated for the population and each type of publication. Information on the population of Qatar was gathered from the website of Qatar Statistics Authority to determine the correlation of papers published per 1000 population. RESULTS: The number of publications retrieved from PubMed was not particularly different for each variation of search carried out. However, the most representative number of publications was retrieved upon searching for "Qatar*" in the "Affiliation" or in "Title/Abstract" fields. Between the years 2000 and 2012, the total number of biomedical publications from Qatar increased 24 times with an average APC of 33.4%, which was found to be more than the APC of the population in Qatar which averaged at 9%. The number of biomedical publications per 1000 population increased from 0.02 in 2000 to 0.15% in 2012. Most publications retrieved were humans studies and occasionally were for other animal species. Cancer publications in Qatar represented 16.9% of the total publications and the number of cancer publications per 1000 population increased from 0% in 2000 to 0.02% in 2012. Publications classified as clinical trials represented 4.6% of Qatar biomedical publications. Publication of cancer clinical trials were very rare (0.4%). CONCLUSIONS: Despite the obvious increase in Qatar biomedical and cancer publications in PubMed, the absolute numbers were relatively small. While strategies are in place, leaders of Qatar biomedical research need to consider increasing cancer research and clinical trials to meet the country's needs. Linking research output to researchers, research facilities and research funding is needed.

Gastric carcinoma at Tanta Cancer Center: a comparative retrospective clinico-pathological study of the elderly versus the non-elderly.

BACKGROUND AND AIMS: To study the clinico-pathological features, treatments and outcomes of gastric carcinoma (GC) in the elderly (⩾65 years) and the non-elderly Egyptian patients. METHODS: This retrospective cohort study included 168 patients with histologically confirmed GC treated at Tanta Cancer Center between 2003 and 2007. RESULTS: Compared to the non-elderly, elderly patients had significantly higher proportion of tumors involving the cardia (p=0.034) and of adenocarcinoma NOS histology (p=0.032). Treatments were largely comparable in the two groups. Response to palliative chemotherapy was achieved in 44.4% of the elderly and 25.5% of the non-elderly patients (p=0.417). The median overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 6, 17 and 3 months, respectively. The median OS was 4 months in the elderly compared to 9 months in the non-elderly (p=0.005). The median DFS was 4 months in the elderly compared to 20 months in the non-elderly (p=0.004). The median PFS was 2 months in the elderly compared to 3 months in the non-elderly (p=0.685). In multivariate analysis, poor performance status was an independent predictor of poor OS, DFS and PFS. Non-curative or no surgery and lack of chemotherapy use were independent predictors of poor OS. Age was an independent predictor of poor DFS. CONCLUSIONS: Compared to the non-elderly, GC in the elderly has similar clinico-pathological characteristics and exhibits comparable outcomes with the same treatment options. Treatments should be tailored to each patient.

Treatment outcomes of female germ cell tumors: the Egyptian National Cancer Institute experience.

INTRODUCTION: Female germ cell tumors (GCTS) are rare tumors that carry a good prognosis. AIM: To report the experience of the Egyptian National Cancer Institute (ENCI) in managing female GCTs. METHODS: This retrospective study included 19 females with ovarian GCTs presenting to the ENCI between 2006 and 2010. RESULTS: The median age was 23years. Ovaries were the primary site in all patients. Dysgerminoma and teratoma were the predominant pathologies followed by mixed GCT in females. Unilateral ovariectomy or ovarian tumorectomy were the classic surgical procedures with R0 resection being feasible in most cases. Surveillance was adopted in six patients with stage I disease. Chemotherapy was administered in 63% of ovarian GCTs with BEP being the commonest regimen with reasonable tolerability and good response rates. The median OS and EFS were not reached. The projected 5-year OS rate was 93.8%. Both OS and EFS were better in patients responding to chemotherapy than non-responders (p<0.002). Stage of disease did not significantly affect OS or EFS. CONCLUSIONS: Female GCTs rarely affect Egyptian females. They have good prognosis.

Role of Ki67 in predicting resistance to adjuvant tamoxifen in postmenopausal breast cancer patients.

INTRODUCTION: Breast cancer (BC) is a major health problem in Egypt and worldwide. Its prognosis depends not only on tumor stage but also on tumor biology. AIM: To correlate the expression of Ki67 with the clinical outcomes of early hormone-receptor positive postmenopausal BC patients who are receiving tamoxifen. METHODS: This cohort study included 70 patients. They were followed up for a minimum of 2 years. Ki67 was assessed on paraffin-embedded blocks using immunohistochemistry methods. RESULTS: The median Ki67 value was 22.5% (IQR, 10%-50%). Ki67 was significantly higher in patients with HER2 positive tumors compared to HER2 negative tumors. After a median follow up period of 53 months, 22 patients (31%) developed disease recurrence either loco-regional or distant in 5.7% and 30%, respectively. Recurrent patients had significantly higher tumor stage, nodal stage and Ki67 values compared to non-recurrent cases. The 2-, 3- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 100% & 91%, 98% & 84% and 77% & 59%, respectively. DFS was significantly worse with higher TNM stage, lower ER expression and higher Ki67 values. OS was significantly worse in patients with Ki67 values ≥ 30%. Ki67 ≥ 30% was an independent predictor of recurrence, poor DFS and OS. CONCLUSION: High Ki67 expression is predictive of poor prognosis and of resistance to adjuvant tamoxifen therapy in postmenopausal BC. We recommend considering Ki67 as one of the risk factors that guide adjuvant treatment decisions.

Breast cancer laterality among Egyptian patients and its association with treatments and survival.

BACKGROUND AND AIM: Breast cancers (BCs) involve the left side (LS) more than the right side (RS). Among the Egyptians, neither BC laterality nor its association with demographic factors, tumor locations, treatments and outcomes were previously reported. PATIENTS AND METHODS: Laterality was analyzed among 5459 BCs from the Gharbiah population-based cancer registry covering >5% of the Egyptian population. Cox proportional model was used to assess the independent effect of stage, ER, and laterality on overall survival (OS). RESULTS: In Egypt, BCs involve LS more than RS with LS-to-RS ratio (LRR) of 1.16. LS predominance was evident among men and women and both younger (< 45 years) and older patients. HER2 over-expression and ductal cancers were significantly more in RSBCs while lobular cancers were significantly more in LSBCs. There were no significant differences in localization within the breast between LSBCs and RSBCs (p = 0.51). LS predominance was noticed across all subgroups except in patients with HER2 positive tumors (LRR = 0.63; p = 0.02). OS was significantly better in stage II and ER positive tumors than stage III and ER negative tumors. Despite OS of LSBCs being generally lower than RSBCs, this was not statistically significant. The significant impact of stage on OS was lost in LSBCs. CONCLUSIONS: Among Egyptian patients, the left breast is at greater risk of cancer than the right one. Despite right-sided tumors seemed more aggressive, Left-sided ones tend to confer worse survival than right-sided tumors.

Small intestinal cancers among adults in an Egyptian district: a clinicopathological study using a population-based cancer registry.

BACKGROUND: Small intestinal cancers (SICs) are very rare all over the world and little is known about them in Egypt. METHODS: This a retrospective study. Between 2000 and 2002, 30 cases with SICs were identified in the Gharbiah population based cancer registry (GPBCR); 17 cases of whom were treated at Tanta Cancer Center (TCC). RESULTS: The median age was 51 years with female predominance. The duodenum was the commonest site (43%) followed by the ileum then the jejunum. Adenocarcinoma (AC), carcinoids, gastrointestinal stromal tumors (GISTs), lymphoma and sarcoma represented 50%, 10%, 17%, 13% and 10% respectively. Abdominal pain was the commonest symptom and localized disease was the commonest presentation. Surgery, chemotherapy and radiotherapy were employed in 65%, 35% and 0% of patients, respectively. The median overall survival and progression free survival (OS, PFS) were 18 and 15 months (95% CI: 10.4-25.6 and 3.6-26.4), respectively. AC had inferior OS and PFS to other histologies (p = 0.08 and 0.12, respectively). Also, duodenum subsite was inferior in OS and PFS to other sites (p = 0.25 and 0.35, respectively). CONCLUSIONS: SICs in Gharbiah, Egypt are characterized by predominance of female gender and adenocarcinoma histology. One year survival is 64% with a poor outcome for adenocarcinoma and duodenal subsite.

Adherence of non-pharmaceutically sponsored oncology trial protocols to the International Conference on Harmonization (ICH) guidelines in an academic institution outside the ICH jurisdictions and the impact of IRB implementation on this adherence.

PURPOSE: To assess adherence of non-pharmaceutically sponsored trials (non-PSTs) to ICH protocol structure guidelines and to estimate the effect of implementing Institutional Review Board's (IRB) review on this adherence. METHODS: This is a retrospective exploratory study where 60 non-PST clinical trial protocols (CTPs) were reviewed and halved to IRB-reviewed CTPs (IRCTPs) and non-IRB-reviewed CTPs (non-IRCTPs). Adherence score (AS) was calculated as the number of fulfilled items or sub-items divided by their total number. RESULTS: Three adherence patterns were encountered: (1) items consistently present in both groups e.g. general and background information, objectives, inclusion criteria and intervention details, (2) items consistently absent in both groups and included contact information of investigators and trial sites, product accountability, randomization codes' management, interim analyses and many other statistical aspects, and (3) items variably present in both groups where the effect of IRB was verifiable. Trial site details, potential benefits, discontinuation and exclusion criteria, and follow up for adverse events were more encountered in IRCTPs than non-IRCTPs. Withdrawal criteria and monitoring of treatment compliance showed a reverse pattern (p<0.05 for all). The total AS, administrative AS and ethics AS for IRCTPs was 43%, 22% and 70% compared to 38%, 16% and 33% for non-IRCTPs (p<0.003, <0.001, 0.004), respectively. The scientific AS was 54% for both groups (p=0.87). CONCLUSIONS: IRB-implementation at NCI-Egypt improved ethical and administrative sections of academic protocols. However, this improvement is modest and needs further actions including adoption of protocol templates. Scientific sections were as good after IRB-implementation as they were before that.

Primary gastrointestinal lymphoma in an Egyptian district: a study using a population-based cancer registry.

INTRODUCTION: Gastrointestinal lymphoma (GIL) is the most common extranodal form of non-Hodgkin's lymphoma (NHL) with geographical and age variation of its various subtypes. AIM: To study GIL in Gharbiah, Egypt and to recognize the treatments employed and their outcomes including survival. METHODS: This is a retrospective study. Between 2000 and 2002, 40 adult patients with GIL were identified in the Gharbiah population based cancer registry (GPBCR); 26 cases of whom were treated at Tanta Cancer Center (TCC). RESULTS: GIL in Gharbiah, Egypt represented 6.2% of all GIT cancers. The median age was 47 years with slight male predominance. The commonest primary site was the stomach followed by the colon/rectum then the small intestine (67.5%, 25% and 7.5%, respectively). The commonest histological subtypes were the diffuse large B-cell (41.5%) followed by marginal zone B-cell (39%). The commonest symptoms were abdominal pains followed by vomiting. Only 18% of GILs were surgically resected. Most patients (77%) received chemotherapy with a 60% complete response (CR) rate. Once in CR, relapses are occasional. The median overall survival (OS) and progression free survival (PFS) were 31 and 14 months (95% CI, 13.2-48.7 and 6.4-21.6 months, respectively). Gastric primary site and diffuse large B cell subtype carry a non-significant worse OS and PFS than those of other sites and subtypes. CONCLUSIONS: GILs in Gharbiah, Egypt are characterized by predominance of male gender, gastric site and marginal zone histology. Survival is worse for gastric and diffuse large B-cell GILs compared to other sites and histologies.

Fasting among Muslim cancer patients during the holy month of Ramadan.

BACKGROUND AND OBJECTIVE: Muslims constitute more than 20% of the world's population and have a significant share of its cancer cases. Many Muslim cancer patients witness the fasting month of Ramadan but we do not know which individuals elect to fast. DESIGN AND SETTING: Cross-sectional study conducted among Muslim cancer patients at the National Cancer Institute (NCI), Egypt, during Ramadan, Hijri 1430 (the month of fasting) August-September 2009. SUBJECTS AND METHODS: One-hundred and two patients being treated at the NCI were interviewed. The most common diagnoses were breast cancer (31%), acute leukemia (24%), colorectal cancer (7%), non-Hodgkin lymphoma (5%), bladder cancer (4%), lung cancer (4%), and laryngeal cancer (4%). The two sexes were equally represented and so were metastatic and nonmetastatic diseases. The outpatient:inpatient ratio was 3:1. Treatments being received by these patients included chemotherapy, radiotherapy, hormonal therapy, and nonspecific therapy in 42%, 31%, 10%, and 17%, respectively. Other concomitant diseases were present in 22% of the patients. RESULTS: While 40% of patients did not fast at all during Ramadan, 36% and 24% were partial and complete fasters, respectively. Female patients, those with performance status (PS) 0 to 1, those whose disease was a nonmetastatic solid tumor, and those receiving non-intravenous chemotherapy as outpatients were more likely to be fasting than their corresponding counterparts. Being a female, having PS 0 to 1, and receiving treatment as an outpatient were the only factors that were significant on multivariate analysis. Only 46% of patients sought the treating oncologist advice on whether they could fast. CONCLUSIONS: Most cancer patients fast during Ramadan, but only half of them discuss the issue with their oncologists. We hope that our study stimulates more research on this topic.

Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue.

Breast cancer (BC) is the most common neoplasm among women in most developed countries, including Egypt. Elevated levels of certain proteins in human BC are associated with unfavorable prognosis and progressive stages of the disease. The aim of our study was to evaluate the protein expression profile and prognostic significance of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), MMP-9 and membrane type 1-MMP (MT1-MMP) and their interaction in operable BC patients. The protein expression of COX-2, MMP-2 and MT1-MMP were evaluated by western blot technique, whereas enzymatic activity of MMP-2 and MMP-9 was determined by zymography in 47 breast cancer patients as well as normal adjacent tissues. Also, the correlation between these proteins and age, tumor size, LN stage, TNM stage, estrogen receptor, progesterone receptor, disease-free survival, and overall survival (OS) has been investigated. As compared to adjacent normal tissues, COX-2, MMP-2 and MT1-MMP were over-expressed in 43, 64, and 60 % of tumor tissues, respectively. In the same pattern, the activity of MMP-2 (62 %) and MMP-9 (45 %) was elevated in BC tissues. Multivariate analysis showed a positive correlation between the protein expression of COX-2, MMP-2, and MT1-MMP and the activity of MMP-2 and MMP-9 in BC patients. However, the enzymatic activity showed no correlation with clinicopathological features. This study confirms the preclinical evidence that COX-2 increased the expression of MT1-MMP, which in turn activates MMP-2. The lack of correlation with clinicopathological features, OS or disease-free survival ascertains the complexity of tumor progression and metastasis with many pro- and counter regulatory factors.

Epidemiology and management of breast carcinoma in Egyptian males: experience of a single Cancer Institute.

OBJECTIVE: To assess the epidemiological and clinico-pathological features, surgical and reconstructive techniques, adjuvant treatments and clinical outcome of breast carcinoma in males (BCM) at the Egyptian National Cancer Institute (NCI). PATIENTS AND METHODS: Thirty-two males with breast carcinoma presented to NCI between January 2000 and December 2002. They were evaluated by complete history, physical examination, laboratory and radiological investigations. RESULTS: Median age was 59 years. Left sided and retroareolar breast lumps were the commonest presentations. Grade II tumors positive for hormone receptors were very common. Stages I, II, III and IV of the disease were encountered in 6.2%, 34.4%, 34.4% and 25.0% of patients, respectively. Curative surgery was done in 22 patients; they received adjuvant hormonal therapy, chemotherapy and radiotherapy in 22, 16 and 10 patients, respectively. Eight metastatic patients were treated with palliative measures. Surgery was done in 25 patients; the most common procedure was modified radical mastectomy (40.6%). Primary closure was feasible in 17 patients (68%), local flaps were needed in 4 cases (16%), while myocutaneous flap was done in 3 cases (12%). The commonest complication was the development of seroma (9 cases). The overall survival (OS) at 5 years was 65.4%. The disease free survival (DFS) at 5 years was 53.9%. Stage and curative surgery significantly affected OS, while type of surgery was the only variable significantly affecting DFS. CONCLUSION: Male breast carcinoma occurs at older ages than females, usually in advanced stage. This necessitates directing attention of males and awareness on the prevalence and risk factors for this disease.

Prognostic value of serum vascular endothelial growth factor in Egyptian females with metastatic triple negative breast cancer.

OBJECTIVES: The aim of this work was to explore the value of serum vascular endothelial growth factor-A (VEGF-A) in patients with metastatic triple negative breast cancer (TNBC) treated with chemotherapy. The primary end point was overall survival (OS). Secondary end points were response rate (RR), progression-free survival (PFS) and VEGF-A level at baseline, mid-therapy and at the end of therapy. DESIGN AND METHODS: Female patients aged 18 years or above with histologically proven metastatic TNBC were included. Serum VEFG-A levels were measured at baseline, after the 3rd and 6th cycles of FAC chemotherapy regimen (Fluorourcil, Adriamycin, and Cyclophamide). RESULTS: The overall RR was 57%. The median PFS and OS were 7 and 11.2 months, respectively (95% CI: 4.3-9.7 and 3.8-18.5 months, respectively). Patients whose disease progressed despite therapy had a significantly higher baseline VEGF-A level than those who did not progress. VEGF-A level did not drop with continuation of therapy. Patients with high VEGF-A level had a significantly lower PFS but not OS than patients with low levels. CONCLUSION: The outcome of metastatic TNBC is poor with FAC chemotherapy regimen. Alternative chemotherapeutic regimens and novel therapeutic approaches including targeting of VEGF and/or its receptors are warranted.

The present and the future of breast cancer burden in the Kingdom of Saudi Arabia.

BACKGROUND: Despite the low cancer incidence in the Kingdom of Saudi Arabia (KSA), the country must be ready to face the challenge of foreseeable increase in cancer burden attributed to growth and aging of population. This work was designed to study female breast cancer as a model to assess future cancer burden and the impact on healthcare resources. METHODS: Cancer statistics for the KSA were compared with that for the USA. The Joinpoint regression program was used to identify changes in secular trends, while the GLOBOCAN 2002 software projected future incidence and mortality. RESULTS: In the KSA, the age-standardized cancer rate (ASR) is 61 per 100,000 population, while the median age at diagnosis is 54 and 49 years for men and women, respectively. Fitting the ASR for breast cancer did not show any significant trend over a 10-year calendar period (16.2-18.2 per 100,000), a pattern that was similar to that for the USA in the prescreening mammography era. Considering the growth and aging of population and using conservative estimates for the annual percent change in incidence (increase) and mortality (decrease) by 2025, incidence and mortality cases are expected to increase by about 350% and 160%, respectively. CONCLUSION: In developing countries, future cancer rates could demonstrate a considerable increase and enormous demands on healthcare resources. The present work may provide an impetus to study other prevalent cancer types particularly in developing countries.