Epstein-Barr Virus and Breast Cancer: Lack of Evidence for an Association in Iranian Women

Controversies regarding the role of Epstein-Barr virus (EBV) in breast cancer and lack of published literature in this regard in Iran, prompted us to assess EBV presence in 100 breast carcinoma and 42 control biopsies obtained from Iranian women. Breast carcinoma cases were comprised of 81 invasive ductal carcinoma NOS, 9 invasive lobular carcinoma, 1 apocrine carcinoma, 2 cribriform carcinoma, 2 papillary carcinoma and 5 mucinous carcinoma. Control biopsies consisted of 13 fibroadenoma, 9 benign epithelial proliferation (adenosis and sclerosing adenosis), 9 usual ductal hyperplasia, 4 atypical ductal hyperplasia, 4 non-proliferative fibrocystic changes and 3 normal breast tissue. To identify EBV-infected cells we applied immunohistochemical analysis, using monoclonal antibody against Epstein-Barr virus-encoded nuclear antigen 2 (EBNA-2) and latent membrane protein 1 (LMP-1). Further, polymerase chain reaction (PCR) was used to amplify EBV DNA, with primers that cover the EBV encoded RNA (EBER) and BamHIW regions. EBNA-2 and LMP-1 immunohistochemistry were negative in all breast cancer and control specimens. Using PCR, none of the 100 breast cancer samples or the 42 control specimens showed detectable EBV DNA. These results indicate that EBV may not play a significant role in the etiology of breast cancer in Iranian women.     

Relationship between Depression and Self-care in Iranian Patients with Cancer

Background: The current cross-sectional study was carried out to determine relationships between self-care and depression in patients with cancer. Materials and Methods: From October to December, 2015, 380 patients with cancer admitted to the associated university’s medical sciences hospitals (Sari, Iran), were entered into the study using non random sampling (accessible sampling). Data were collected by demographic questionnaire, Center for Epidemiological Studies Depression Scale (CES-D) and a Self-care Questionnaire. Results: Males (48.4±13±39; CI95: 46.4-50.4) were older than females (45.3±18.4; CI95:42.8-47.9). Spearman correlation analysis results showed that there was a significant negative correlation between self-care and depression (r= -0.134, P<0.05) and also a significant inverse relationship between physical (r= -0.166, P=0.001), psychological (r= -0.207, P<0.001) and emotional self-care (r= -0.179, P<0.001) with depression. Conclusions: It appears that self-care measures such as training of physical exercises, promotion of physical self-care, holding counseling sessions and psychotherapy can reduce depression levels.     

Lack of Association between High-risk Human Papillomaviruses and Oral Squamous Cell Carcinoma in Young Japanese Patients

Background: Human papillomaviruses (HPV) may play an important role as one of the possible etiologiesof oral squamous cell carcinoma (OSCC). The present study aimed to investigate the association between HPVand OSCC in young Japanese patients by examining the presence of HPV DNA and surrogate markers in OSCCtissues. Materials and Methods: Forty young patients with OSCC whose surgical specimens were available wereanalyzed and compared with 40 patients randomly recruited from a pool of patients aged >40 years. HPV DNAwas detected using the polymerase chain reaction-based AMPLICOR® HPV test, and surrogate markers ofHPV infection were analyzed using immunohistochemical techniques to detect p16INK4a and p53. Results: Onlytwo (5%) young patients and one (2.5%) older patient were positive for HPV DNA. p16INK4a overexpressionwas identified in six (15%) young patients. p53 staining levels were not high in tissues of most young patients(27 patients, 67.5%). HPV DNA status did not significantly correlate with p16INK4a expression levels. Profiles ofincreased levels of p16INK4a expression with diminished levels of p53 staining were not associated with the presenceof HPV DNA. The combined p53 with p16INK4a profiles were significantly correlated with alcohol consumptionin younger patients (p=0.006). Conclusions: Results of the present study indicate that HPV is less likely to causeOSCC in young Japanese patients, and the p16INK4a expression level is not an appropriate surrogate marker forHPV infection in OSCC.     

Survival Rates for Breast Cancer in Iranian Patients: a Meta- Analysis

Background: Breast cancer is the most common cancer among Iranian women. Since development of the disease in Iranian women occurs relatively early, the survival rate matters considerably. In different countries, survival of breast cancer patients varies considerably. Therefore, the one-year, three-year, five-year, and ten- year survival rates for breast cancer in Iran were assessed using a meta-analysis. Materials and Methods: This systematic review and meta-analysis was based on valid Iranian sources including SID, MAGIRAN and IRANMEDEX, along with reliable English databases, namely, PUBMED and SCOPUS. In domestic databases, a search was conducted based on key words of breast cancer and survival rate, and in international databases, with "breast cancer" and the equivalent of "neoplasm" of Mesh Word, "survival rate" and "Iran. " Then all reviewed papers and theses which met the inclusion criteria were selected for investigation. To conduct the analysis STATA 11.2 software and random-effects models were used. Results: In 24 studies, 22,745 participants were included. The one-year, three-year, five-year and ten-year survival rates were 0.956, 0.808, 0.695 and 0.559, respectively. The minimum and maximum survival rates for 5-years were 0.48 and 0.87. The average age of the onset of the disease was 48.3. Conclusions: As in Iran, since the onset of the disease is at low age, in spite of the relatively high survival rate as compared to other cancers, prevention and screening programs at early age for early stage diagnosis seems necessary.     

年龄与乳腺癌患者保乳术后局部复发风险的Meta分析

[目的]使用Meta分析方法分析年龄与乳腺癌患者保乳术后局部复发的关系。[方法]检索关于年龄与乳腺癌保乳术后具有复发关系的文献,采用Meta分析。[结果]共有5篇文献符合纳入标准,乳腺癌保乳术后患者5188例,其中＂年轻＂患者380例,＂年老＂患者4808例。Meta分析显示相对于＂年老＂患者,＂年轻＂患者术后局部复发风险增加（OR=3.73,95%CI：1.64～8.49）。以40岁为界限,≤40岁组术后局部复发风险增加（OR=4.10,95%CI：1.55～10.85）。[结论]＂年轻＂乳腺癌患者保乳术后局部复发风险增高,≤40岁患者局部复发明显高于〉40岁患者。     

Estimation of the Cure Rate in Iranian Breast Cancer Patients

Background: Although the Cox’s proportional hazard model is the popular approach for survival analysis to investigate significant risk factors of cancer patient survival, it is not appropriate in the case of log-term disease free survival. Recently, cure rate models have been introduced to distinguish between clinical determinants of cure and variables associated with the time to event of interest. The aim of this study was to use a cure rate model to determine the clinical associated factors for cure rates of patients with breast cancer (BC). Materialsand Methods: This prospective cohort study covered 305 patients with BC, admitted at Shahid Faiazbakhsh Hospital, Tehran, during 2006 to 2008 and followed until April 2012. Cases of patient death were confirmed by telephone contact. For data analysis, a non-mixed cure rate model with Poisson distribution and negative binomial distribution were employed. All analyses were carried out using a developed Macro in WinBugs. Deviance information criteria (DIC) were employed to find the best model. Results: The overall 1-year, 3-year and 5-year relative survival rates were 97%, 89% and 74%. Metastasis and stage of BC were the significant factors, but age was significant only in negative binomial model. The DIC also showed that the negative binomial model had a better fit. Conclusions: This study indicated that, metastasis and stage of BC were identified as the clinical criteria for cure rates. There are limited studies on BC survival which employed these cure rate models to identify the clinical factors associated with cure. These models are better than Cox, in the case of long-termsurvival.     

Diagnostic Classification Scheme in Iranian Breast Cancer Patients using a Decision Tree

Background: The objective of this study was to determine a diagnostic classification scheme using a decisiontree based model. Materials and Methods: The study was conducted as a retrospective case-control study inImam Khomeini hospital in Tehran during 2001 to 2009. Data, including demographic and clinical-pathologicalcharacteristics, were uniformly collected from 624 females, 312 of them were referred with positive diagnosisof breast cancer (cases) and 312 healthy women (controls). The decision tree was implemented to develop adiagnostic classification scheme using CART 6.0 Software. The AUC (area under curve), was measured as theoverall performance of diagnostic classification of the decision tree. Results: Five variables as main risk factorsof breast cancer and six subgroups as high risk were identified. The results indicated that increasing age, lowage at menarche, single and divorced statues, irregular menarche pattern and family history of breast cancer arethe important diagnostic factors in Iranian breast cancer patients. The sensitivity and specificity of the analysiswere 66% and 86.9% respectively. The high AUC (0.82) also showed an excellent classification and diagnosticperformance of the model. Conclusions: Decision tree based model appears to be suitable for identifying riskfactors and high or low risk subgroups. It can also assists clinicians in making a decision, since it can identifyunderlying prognostic relationships and understanding the model is very explicit.     

The Role of Human Papillomaviruses in Cancer

The human papillomavirus (HPV) has been implicated in the development of an estimated 10% of cancers worldwide. Both epidemiologic and molecular evidence have conclusively demonstrated that oncogenic HPV is the central causal agent of cervical cancer and of a substantial proportion of many other anogenital neoplasms. In fact, it is believed that HPV is the necessary cause of cervical cancer, which has implications for the prevention, screening, and treatment of this disease, especially for its precursor lesions. This has led to the possibility of using HPV DNA testing in screening and as a method of triaging abnormal Papanicolaou (Pap) tests. Research into the development of vaccines is also currently very active. HPV has been implicated in the genesis of several other cancers, such as oral and non-melanoma skin malignancies. However, research is yet to provide a consistent body of unequivocal evidence for a causal role that could lead to public health policy.     

Evaluation of Environmental Risk Factors for Prostate Cancer in a Population of Iranian Patients

Background: The Prostate cancer is the 2nd most common cancer worldwide for males, and the 5th mostcommon cancer overall, with an estimated 900,000 new cases diagnosed in 2008 (14% of the total in males and 7%of the total overall) aim of this study was to assess some of the most proposed environmental factors influencingthe incidence of prostate cancer among Iranian men. Smoking, opioids, occupation and living location wereconsidered as studied risk factors of the prostate cancer in this research. Material and methods: Two groupsof affected men with prostate cancer and controls aged 50-75 years referred to medical clinics were subjectsin this case-control study. Living and working place, smoking and drug consuming habits were assessed forany associations with prostate cancer. Results: The largest number, of patients, in order, belonged to Tehran,provincial capitals, major industrial cities, small towns and villages, respectively. The disease showed links withsmoking and drugs with a significant difference between controls and patients (P value <0.0001). Conclusions:Our recent evidence duplicates previously done researches confirming the serious adverse effects of smokingand drugs on the prostate cancer occurrence in Iranian men. Living place bearings some hazardous behaviorswhich increases the rate of diseases as well as advanced chance for associated cancers like prostate.     

Molecular and Serological Prevalence of HCMV in Iranian Patients with Breast Cancer

Background: Human cytomegalovirus (HCMV) is prevalent viral infection involved in several human cancers including breast cancer. The presence of HCMV genome in breast cancer tissue and footprint of viral last exposure patient’s serum are considered as important factor in the process of breast cancer development. Objectives: This study aimed to investigate molecular and serological epidemiology of HCMV in patients with breast cancer in Iran for first time. Methods: In our case-control study, 98 samples of breast tissue, including 49 cancerous (case) and 49 adjacent non-cancerous tissue were collected (control). In addition, we collected sera samples from all patients (n=49) and healthy individual (n=49). Seroprevalence of HCMV was assessed by Enzyme-linked immunosorbent assay (ELISA) and detection of HCMV genome was performed using Nested-PCR method. Results: HCMV genome found in 16.3% (8/49) of cases tissue and 2% (1/49) of controls tissue. In patients group, the levels of anti-CMV IgG and IgM were 93.9% and 2% compared to 69.4% and 4.1% in healthy individuals, respectively. There was a statistically difference between the anti-CMV IgG in patients and healthy control (p= 0.002). We found 75% of (6/8) HCMV genome positive PCR samples were also positive for their anti-CMV IgG in cases which was statistically significant (p= 0.01).  Conclusions: Our result showed significant presence of HCMV genome and anti-CMV IgG in patients, supporting the role of HCMV in breast cancer.     

Serum Levels of G-CSF and IL-7 in Iranian Breast Cancer Patients

Introduction: Breast cancer cells and tumor stroma produce different cytokines and soluble factors. Cytokines,while playing crucial roles in immune responses to tumors, also favour tumor growth and progression. IL-7and G-CSF are two cytokines that may exert influences on the pathophysiology of breast cancer. Materials andMethods: Sera were collected from 136 females with breast cancer before receiving chemotherapy or radiotherapy.The control group comprised of 60 healthy age-matched females without any acute or chronic diseases withno family history of breast cancer. Serum levels of IL-7 and G-CSF were measured by commercial enzymelinked immunosorbent assay. Results: While there was no significant difference in the level of G-CSF betweenpatients (92.81±594.54 pg/ml) and controls (0.00 pg/ml), G-CSF level in sera of patients with advanced stagesof breast cancer was elevated compared to early stages (p=0.0001). Moreover, the highest level of G-CSF wasseen in patients with N3 phase tumors (p=0.0001). IL-7 was slightly but not significantly higher in the controlgroup (0.04±0.11 pg/ml) in comparison with patients (0.02±0.10 pg/ml). Interestingly, a significant increase inthe level of IL-7 in patients with skin involvement was observed (p=0.001). Conclusion: Our results showed anelevation of G-CSF in sera of patients with advanced stages of tumor, while IL-7 elevation correlated with skininvolvement of breast cancer. IL-7 can be produced by keratinocytes in skin tissue and may be involved in thepathologic establishment of metastatic tumor cells in skin.     

Breast Cancer Risk Factors in Women Participating in a Breast Screening Program: a Study on 11,850 Iranian Females

The incidence rate of breast cancer in developed countries is almost three-fold higher than in developingcountries. Iran has had one of the lowest incidence rates for breast cancer in the world, but during the recentdecades a marked increase has been seen. The purpose of this study was to investigate some established riskfactors of breast cancer in Iranian women. A study of 11,850 women participating in abreast screening programwas conducted. The 197 women diagnosed with breast cancer and 11,653 healthy women were compared. Logisticregression was performed to investigate associations of reproductive and anthropometric factors with breastcancer risk. Family history of breast cancer (OR=1.94 , 95%CI=1.35-2.78), occupation (OR= 1.65,95%CI=1.20-2.25), education level (OR=0.50,95%CI=0.28-0.91), parity (OR=0.27, 95%CI=0.12-0.59), menopausal status(OR=3.15, 95%CI=2.35-4.21), age at menarche (OR=0.33, 95%CI=0.15-0.70), and age at the first pregnancy(OR=4.10 , 95%CI=1.13-14.77) were related to the risk of breast cancer. Decrease in parity may to some extentexplain the rising trend of incidence of breast cancer incidence in Iranian women.     

Risk Factors for Tamoxifen-Induced Ovarian Hyperstimulation in Breast Cancer Patients

IntroductionAdjuvant endocrine therapy is an integral component of care for hormone-dependent breast cancer. Tamoxifen is a potent inducer of ovarian function and consequent hyperestrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenon remain unclear.Patients and MethodsData of patients younger than 60 years who received adjuvant tamoxifen therapy for hormone-dependent breast cancer (stages 0-III) and who underwent regular follow-up of laboratory results for follicle-stimulating hormone and estradiol levels were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinicopathologic factors related to ovarian hyperstimulation.ResultsAmong 205 patients, 19 (9.3%) showed high values of serum estradiol during tamoxifen therapy. The mean (± SD) serum concentrations of estradiol and follicle-stimulating hormone were 1047.97 ± 638.8 pg/mL and 11.5 ± 7.3 mIU/mL, respectively. A mean of 400.83 days elapsed from the start of the single administration of tamoxifen to the initial detection of a high concentration of estradiol. Univariate and multivariate analyses showed that younger age (< 40 years) and only endocrine therapy without chemotherapy were significantly related to a higher prevalence of ovarian hyperstimulation (P = .015, relative risk = 7.49 for age < 40 years; P = .017, relative risk = 32.9 for no chemotherapy). Pathologic stages and tumor characteristics were not related to the manifestation of ovarian hyperstimulation.ConclusionYoung age (< 40 years) and endocrine treatment without chemotherapy were risk factors for the incidence of ovarian hyperstimulation during tamoxifen treatment. Close monitoring of endocrine parameters during treatment with tamoxifen especially in this patient group is essential.     

Nutrient Patterns and Risk of Breast Cancer among Iranian Women: a Case- Control Study

Objective: To explore the role of nutrient patterns in the etiology of breast cancer (BCa) among Iranian women.Methods: The study included 134 newly diagnosed cases of BCa and 267 hospitalized controls. A validatedsemi-quantitative food frequency questionnaire (FFQ) was used to assess dietary intake. Nutrient patterns were obtainedusing principal component analysis using Varimax rotation and logistic regression was performed to estimate breastcancer risk. Results: We identified 4 major nutrient patterns. First was high in consumption of vitamins B1, B2, B3, B5,B6, B9, C, magnesium, iron, carbohydrate, fiber, selenium, zinc, protein, potassium, and calcium. The second nutrientpattern included Vitamins B12, A and cholesterol, while the third featured vitamin D, EPA and DHA. The fourth wascharacterized by vitamin E, MUFA and saturated fatty acids. After adjusting for age, patterns 1 and 3 were associatedwith a lower risk of BCa (OR=0.51, 95% CI: 0.33- 0.80, P=0.003, OR=0.64, 95% CI: 0.42- 0.98, P= 0.04 respectively).However, after further adjustment for all confounders in multivariate analysis, the association remained significant onlyfor pattern 1 (OR=0.52, 95% CI: 0.32- 0.82, P=0.006). Conclusion: Adherence to a nutrient pattern rich in vitamin B,minerals and fiber is associated with a lower risk of breast cancer.     

Roles of Human Papillomaviruses and p16 in Oral Cancer

Head and neck cancer, including oral cancer, is the sixth most common cancer in humans worldwide. Morethan 90% of oral cancers are of squamous cell carcinoma type. Recent studies have shown a strong relationshipbetween human papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal squamouscell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Moreover, the incidence of HPV-relatedOSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades. p16, atumor suppressor gene, normally functions as a regulator of the cell cycle. Upon infection with high-risk typesof HPV (HR-HPV), particularly types 16, 18, 31, 33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expressionof p16 is aberrantly overexpressed. Therefore, the expression of p16 is widely used as a surrogate marker forHPV infection in head and neck cancer.     

人类乳头状瘤病毒感染和食管癌发生的相关性研究路径

简介安阳市肿瘤医院与北京大学临床肿瘤学院，开展人类乳头状瘤病毒（HPV）感染和食管癌发生的相关性研究课题的设计思想，阐述立项依据、技术路线、主要研究内容以及关键问题等。     

BRCA1 and BRCA2 Common Mutations in Iranian Breast Cancer Patients: a Meta Analysis

Background: To date several common mutations in BRCA1 and BRCA2 associated with breast cancer havebeen reported in different populations. However, the common BRCA1 and BRCA2 mutations among breastcancer patients in Iran have not been described in detail. Materials and Methods: To comprehensively assessthe frequency and distribution of the most common BRCA1 and BRCA2 mutations in Iranian breast cancerpatients, we conducted this meta-analysis on 13 relevant published studies indentified in a literature searchon PubMed and SID. Results: A total of 11 BRCA1 and BRCA2 distinct common mutations were identified,reported twice or more in the articles, of which 10 (c.2311T>C, c.3113A>G, c.4308T>C, c.4837A>G, c.2612C>T,c.3119G>A, c.3548A>G, c.5213G>A c.IVS16-92A/G, and c.IVS16-68A/G) mutations were in BRCA1, and 1(c.4770A>G) was in BRCA2. The mutations were in exon 11, exon 13, intron 16, and exon 20 of BRCA1 andexon 11 of BRCA2. All have been previously reported in different populations. Conclusions: These meta analysisresults should be helpful in understanding the possibility of any first true founder mutation of BRCA1/BRCA2in the Iranian population. In addition, they will be of significance for diagnostic testing, genetic counseling andfor epidemiological studies.     

Risk Stratification of Patients With Early Breast Cancer

BackgroundSentinel lymph node biopsy (SLNB) is the standard procedure performed to stage the axillae, and axillary node clearance (ANC) or radiotherapy is the treatment for nodal involvement. The aims of this study were to assess (1) the role of preoperative axillary ultrasonography (US), (2) the number of positive lymph nodes on ANC after either positive SLNB results or preoperative ultrasonographically guided nodal biopsy, and (3) the role of ANC in patients with node-positive breast cancer.Patients and MethodsAll patients with invasive breast cancer and axillary node involvement (but clinically negative nodes on presentation) who underwent ANC between January 2008 and December 2009 were identified, and information regarding clinicopathologic parameters and the nodal yield was collected. ANC was performed for 3 groups: patients with micrometastasis seen in SLNB specimens, macrometastasis seen in SLNB specimens, and positive axillary nodes detected on US biopsy.ResultsANC was performed 141 times over the 2-year period. Forty-two percent of axillary node involvement was diagnosed by biopsy or preoperative US, and 40% of these patients received neoadjuvant chemotherapy. The remainder of cases were diagnosed by SLNB: 30% had micrometastases and 70% had macrometastases. Fifty percent of cancers with an ultrasonographic diagnosis of lymph node involvement were high grade and 56% had 4 or more positive nodes on ANC; this was significantly higher than in patients with positive SLNB results (P = .0001). Only 20% of patients with macrometastases on SLNB had 4 or more positive nodes in comparison with 56% with positive axillary lymph nodes by US (P < .0001).ConclusionThe routine use of preoperative axillary US and biopsy of abnormal nodes helps in identifying high-risk patients and thus aids in planning treatment.