Iranian Breast Cancer Research Articles

Quality of Life in Iranian Breast Cancer Survivors and Affecting Factors: A Review Article

Introduction: The breast cancer is the first common cancer among Iranian women, accounting for 24.4% of all cancers. With the improvement in disease‑free survival with advanced treatment modalities, question of quality of life (QOL) arises. The aim of the present review was assessment QOL of Iranian women with cancer breast and affecting factors.Methods: This study is a review article in which articles about Breast cancer were searched in databases such as Scopus, SID, Magiran, Google Scholar, Pubmed, IranMedex, ScienceDirec from key words of Cancer Brest, Quality of Life, Affecting Factor and Iran were used to search.Results: Twenty-eight studies from 2008 to 2018 on the quality of life of 2226 patients with breast cancer in Iran were conducted. In these studies, five different questionnaires QLQ-C30, SF-36, Ferrans & Power, QLQ-BR23, WHO-QOL 26 to check the quality of life patients were used. Conclusion: Breast cancer affects the quality of life of the patients and reduces it. Psychological and financial support and exercise and health for women experiencing breast cancer diagnosis can have been a positive impact on the disease and the patient’s compliance with the complications of the disease and the treatments.

The effects of psychosexual counseling on sexual quality of life and function in Iranian breast cancer survivors: a randomized controlled trial.

Considering different dimensions of life, special sex life for survivors of breast cancer (BC) is important because their life expectancy has increased. We designed this study to improve the sexual function, satisfaction and quality of sexual life. In a randomized controlled clinical trial study, from a total 286 breast cancer survivors (BCS), 118 women enrolled to the study. After providing informed consent, the participants were randomly assigned either to the intervention group or to the waitlist control group. The intervention consisted of six weekly psychosexual counseling sessions that lasted from 90 to 120min. Data were collected by the demographic and clinical forms, Beck Depression Inventory, Female Sexual Function Index (FSFI), Larson Sexual Satisfaction Questionnaire and sexual quality of life-female (SQOL-F) questionnaire. Mean age of patients in control and intervention groups were 43.8 ± 6.6 and 44.84 ± 6.7, respectively. More than 65% of the patients in the both groups were either normal or showed a low level of depression. Sexual function (FSFI) scores and sexual quality of life (SQOL-F), showed a significant statistic differences after intervention (P < 0.001 in both tools). Sexual satisfaction (Larson) has showed improvement in some subclasses, however, change in total score was not statistically significant (P = 0.073). The psychosexual intervention program was effective in improving sexual function and quality of sexual life among BCS. This intervention has clinical significance as it provided an opportunity for the women to discuss their sexual issues.

Assessment of the fitness of Cox and parametric regression models of survival distribution for Iranian breast cancer patients' data.

Factors affecting the time of survival after breast cancer (BC) diagnosis remain unknown. However, some of the prognostic factors have been identified. The aim of this study was to investigate the effects of biologic and socioeconomic factors on long-term survival of BC patients. This was a descriptive chart review and survey of all women with a confirmed diagnosis of BC registered in Shohada-e-Tajrish Cancer Research Center database from March 2004 to March 2015. The checklist of study consisted of biologic, demographic, reproductive, genetic, medical, and therapeutic information of patients. The minimum time of follow-up was 3 years and the maximum was 10 years. We then evaluated possible associations of these variables with BC survival using Cox and parametric regression models of survival analysis. The study population was 1276 BC patients. Their mean survival was 23 (range 1–120) months. Between the parametric models, Weibull regression model demonstrated the lowest Akaike information criterion and thus the best fit, and tumor size, number of lymph nodes, BC stage, educational level, and high-fat diet were significant in this model. Based on our findings, educational level, consumption of fat, and characteristics of tumor at the time of diagnosis (disease stage, tumor size, number of involved lymph nodes) are the most important prognostic factors affecting long-term survival of BC patients. We suggest that future studies assess the efficacy of possible interventions for these factors.

Association of the study between LncRNA-H19 gene polymorphisms with the risk of breast cancer.

The H19 is a maternally expressed imprinted gene transcribing a long noncoding RNA (lncRNA), which has previously been reported to be involved in tumorigenesis and cancer progression. The aim of this study was to evaluate the associations between two lncRNA-H19 (rs3741219 T>C and rs217727 C>T) gene polymorphisms with the risk of breast cancer (BC). In a case-control investigation, we evaluated 150 BC patients and 100 cancer-free subjects in East Azerbaijan Province of Iran. To assess two gene polymorphisms, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used. The genotype frequencies of two lncRNA-H19 (rs217727 C>T and rs3741219 T>C) gene polymorphisms TT+TC/CC and CC+CT/TT have not shown a statistically significant association with the risk of BC (P=0.065; OR=0.967; 95% CI, 0.938-0.996) and (P=0.510; OR=1.583; 95% CI, 0.399-6.726), respectively. In addition, our findings revealed a significant differences in allele frequencies in lncRNA-H19 rs217727 C>T polymorphism between groups (P=0.033; OR=1.985; 95% CI, 1.048-3.761). Our findings suggested that rs217727 C>T polymorphism may be involved in the pathogenesis of BC, whereas rs3741219 T>C variation may not be involved in the genetic background of BC in Iranian.

Expression of LRP Gene in Breast Cancer Patients Correlated with MRP1 as Two Independent Predictive Biomarkers in Breast Cancer

Background:Breast cancer is the most common malignancy in women. Multidrug resistance (MDR) is still a great obstacle of breast cancer chemotherapy. We have previously shown that multidrug resistance-associated protein 1 (MRP1) is associated with response to neoadjuvant chemotherapy. The lung resistance-related protein (LRP) is identified as a prognostic marker and response to treatment factor which has been studied mainly in hematological malignancy and leukemia. In this study, we aimed to analyze LRP expression and possible correlation between the expression level of this gene with MRP1 as a candidate marker for chemotherapy resistance.Materials and Methods:We collected 54 breast tumors and adjacent normal tissues from Iranian breast cancer patients and Real time RT-PCR was employed to measure the gene expression level in our samples.Results:MRP1 and LRP expression level were significantly lower in tumor tissues of the patients responding to chemotherapy compared to non-responding patients. No relation between the expression level of either of these genes and clinicopathology markers was found.Conclusion:Our results suggest that LRP gene expression is correlated to MRP1 in human breast cancer cells and may affect the clinical response to treatment.

Reconstruction of feminine identity: the strategies of women with breast cancer to cope with body image altered

BackgroundBody image altered is the most important psychosocial concern associated with breast cancer. Yet, there is a paucity of information regarding strategies for coping with this problem. This study aimed to explore Iranian breast cancer women’s strategies for coping with body image altered.MethodsThis qualitative study was conducted in 2016–2017. A purposive sample of 36 women with breast cancer was selected with maximum variation from three health care centers in Alborz Province, Iran. Data were collected by semi-structured interviews and analyzed by performing conventional qualitative content analysis.ResultsThe main theme of the study was “reconstruction of feminine identity” with the six main categories of physical appearance improvement, active information seeking, self-care for managing limits, psychological self-empowerment, maintaining maternal role, and maintaining wife role.ConclusionIranian breast cancer women’s strategies for coping with body image altered are multidimensional and are mainly based on personal resources. Breast cancer women use these strategies to reconstruction of their feminine identity. Health policy-makers can use the findings of the present study to develop interventions and programs for improving breast cancer women’s body image care.

NGS-Based BRCA1, BRCA2, and PALB2 Mutation Testing in Iranian Population With Breast Cancer

Background: Identification of individuals who have a pathogenic mutation in breast cancer susceptibility genes is an important step to take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. Based on the National Comprehensive Cancer Network (NCCN) guideline, genetic testing is deemed suitable for breast cancer patients with young age at onset, positive family history of cancers, male breast cancer, or diagnosis with a multifocal or triple negative breast cancer. Aim: Since, it is not known what proportion of breast cancers in Iran is hereditary and related to mutations in BRCA1/2 and PALB2 genes, therefore, we screened these 3 genes in multiethnic Iranian population to determine the spectrum of the breast cancer susceptibility gene mutations and to further assess the predictive value of the hereditary breast cancer risk criteria for genetic testing. Methods: Next generation sequencing (NGS) was conducted on a population consisted of 299 and 125 breast cancer patients, with and without hereditary cancer risk criteria for genetic testing, respectively. Results: Pathogenic mutation rate was 10.36% in patients with hereditary criteria for breast cancer vs 1.6% in no criteria group ( P = 0.002). All the patients who only met the young age at onset (&lt;40) criterion tested negative for a gene mutation. This is while patients who had only 1 hereditary criterion (OR: 5.48, 95% CI: 1.09, 52.90, P = 0.017) and patients with multiple hereditary criteria (OR: 22.5, 95% CI: 5.19, 201.31, P &lt; 0.0001) had a significantly higher probability of finding a mutation compared with no risk-criteria group. Conclusion: The first application of NGS on Iranian breast cancer population added to the cumulative evidence that BRCA1/2 mutations are seen commonly among Iranian breast cancer patients especially those with hereditary breast cancer criteria and indicated that PALB2 should be concerned in hereditary breast cancer screening alongside BRCA1/2. Investigating the predictive potential of hereditary breast cancer risk criteria our results suggest that offering genetic testing to women with early age at onset of &lt;40 with no other hereditary criteria, may not be cost effective and should be considered for optimization of genetic counseling and genetic testing of the Iranian population.

Survival probability and prognostic factors of Iranian breast cancer patients using cure rate model.

Breast cancer, the major concern of the global health, is the fifth cause of death of women in Iran. In this longitudinal study, 3048 cases of breast cancer who visited and were treated at the Cancer Research Center in Shahid Beheshti University, were studied. During study, 518 patients died. The overall survival rate of 1, 5, 10, 15, and 20-year were 95%, 76%, 59%, 47% and 46%, respectively. A significant relation was observed between survival time and the variables such as age, size of tumor, number of lymph nodes, stage, grade, and lymphovascular invasion.

Investigating of variations in BRCA1 gene in Iranian families with breast cancer.

Background: Breast cancer is one of the most common cancers among Iranian women whose relationship with mutation status in BRCA1 is previously approved. Therefore, screening of the most mutated exons in BRCA1 in hereditary breast cancer patients provides beneficial information about the main disease-causing reason. Methods: A total of 14 Iranian hereditary breast cancer patients participated in this case series study. DNA was extracted from patients’ blood samples for PCR assay. The quality of PCR products was determined using horizontal electrophoresis. Then, sequencing and analysis of the sequencing results were performed to investigate variation status in the sequences. Results: Five variants in 4 patients were found, including 1 pathogenic variant in exon 16 (H1686Q, NM_007294.3:c.5058T>A) and 4 novel intronic variants of uncertain significance (NC_000017.11:41228314G>T, NC_000017.11:41228309C>T, NC_000017.11:41228317G>T, and NC_000017.11:41203042G>A) in BRCA1. This study was the first to report 1 rare pathogenic variant in BRCA1 (H1686Q, NM_007294.3: c.5058T>A) in an Iranian family as the main disease-causing reason. Another interesting finding was non-existence of variations in almost all globally-reported and mutated exons in BRCA1. Conclusion: Investigation of these exons in BRCA1 showed the uniqueness of mutation pattern in Iranian breast cancer patients compared to other world regions. Due to the existence of other BRCA1 exons and also other predisposing genes in breast cancer, the main cause of cancer development in other participants might have been put in those exons and genes. We concluded that the most mutated exons in BRCA1 in Iranian population may not be the same as those found in other parts of the world.

ErbB4 3'-UTR Variant (c.*3622A>G) is Associated with ER/PR Negativity and Advanced Breast Cancer.

A genetic variant may alter a gene expression level and as a result be associated with pathological characteristics in breast cancer. In this research, the frequency and association of the ErbB4 3'-untranslated region (3'-UTR) variant, rs12471583 (c.*3622A>G) was studied in an Iranian breast cancer patients. In silico assessment was performed to predict the function of the rs12471583 variant located on the 3'-UTR of ErbB4. Furthermore, as a case-control study, this polymorphism was genotyped in 243 breast cancer patients and non-cancerous controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The Armitage's trend test and regular association tests were performed to analyze a possible association between the rs12471583 and risk of breast cancer and its relevant pathological traits. The bioinformatics analysis predicted that the rs12471583 SNP is located on the four miRNA binding sites, including miR-511-5p, miR-4659a-5p, miR-4659b-5p, and miR-6830-3p. According to logistic regression tests, the G allele is negatively associated with ER- (OR = 0.20, 95% C.I. = 0.04-0.93, p = 0.026), PR- (OR = 0.31, 95% C.I. = 0.10-0.98, p = 0.039), ER-/PR- (OR = 0.20, 95% C.I. = 0.04-0.93, p = 0.026), and advanced breast cancer (OR = 0.40, 95% C.I. = 0.18-0.85, p = 0.016). It has been found that ErbB4 expression may be linked to unfavorable outcomes in breast cancer. Likewise, our results suggest that the G allele may strengthen miRNA-ErbB4 binding efficiency and as a result reduce expression of ErbB4. This is a possible explanation for the observed association.

CYP2D6*3 (A2549del), *4 (G1846A), *10 (C100T) and *17 (C1023T) genetic polymorphisms in Iranian breast cancer patients treated with adjuvant tamoxifen.

There is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms. Poor metabolizer genotypes may not fully convert tamoxifen to its active metabolite endoxifen and thus have less exposure to anti-estrogen therapy. The present study was conducted to identify the prevalence of CYP2D6 genotypes among Iranian breast cancer patients. A total of 84 estrogen receptor-positive breast cancer patients treated at a referral center in the north of Iran were examined. A peripheral blood sample was obtained from each patient to determine the presence of *3, *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by polymerase chain reaction-based restriction fragment-length polymorphism analysis. Of the four genotypes assessed, CYP2D6*4 was the most common variant and was identified in 41 (48.8%) patients as heterozygous (G/A) and 3 (3.6%) as homozygous (A/A) alleles. CYP2D6*10 heterozygous mutated alleles (C/T) were also a common genotype that presented in 22 (26.2%) of the study subjects. Variant *17 was less common and was detected only as heterozygous (C/T) in 3 patients (3.6%). No CYP2D6*3 heterozygous or homozygous mutated alleles were observed. In conclusion, the frequency of the CYP2D6 nonfunctional alleles *4 and *10 appeared relatively high in Iranian patients with hormone-sensitive breast cancer. This finding may affect the selection of an optimal hormone therapy, as patients with low CYP2D6 pathway activity may not sufficiently convert tamoxifen to its active metabolite endoxifen.

Psychometric evaluation of the Persian version of the Lymphedema Life Impact Scale (LLIS, version 1) in breast cancer patients

BackgroundDespite the high prevalence of lymphedema in Iranian breast cancer patients, there is no valid instrument for measuring quality of life in this population. The aim of this study was to assess reliability and validity of the Persian version of Lymphedema Life Impact Scale (LLIS) in breast cancer patients.MethodsForward-backward procedure was applied to translate The LLIS from English into Persian. The LLIS is an 18-item measure of physical, psychosocial, and functional impairments caused by lymphedema. Experts and patients assessed content and face validity, respectively. Discriminant validity was evaluated by comparing breast cancer patients with and without lymphedema. Convergent validity was assessed by comparing LLIS score with SF-36 (functional component) and the EORTC-QLQ-C30 (functional component). The construct validity also was evaluated using confirmatory and exploratory factor analyses. Internal consistency was evaluated by Cronbach’s alpha coefficient. Stability was assessed by test-retest analysis over a one-week interval in 13 patients.ResultsIn all 446 breast cancer patients were entered into the study. The content and face validity of Persian version of LLIS were acceptable and minor corrections were applied in final version. The questionnaire differentiated well in patients’ with and without lymphedema and lending support to its discriminant validity. Confirmatory factor analysis showed a good fit for the data. Cronbach’s alpha coefficient in physical, psychosocial and functional subscales were 0.873, 0.854 and 0.884 respectively. Intra-class correlation coefficient of total score of the LLIS was 0.96.ConclusionsThe findings of this study suggest a first indication that reliability and validity of the Persian version of LLIS in patients with breast cancer induced lymphedema was good. Application of this instrument for identifying problems of patients with upper extremity lymphedema may be helpful in designing interventions to improve quality of life.

Clinical Outcome and Prognostic Factors in Iranian Breast Cancer Patients After Neoadjuvant Chemotherapy: A Comparative Matched Study

Background: Breast cancer is the most frequent diagnosed solid cancer with the incidence rate of 32 patients in 100,000 among Iranian women. Neo-adjuvant chemotherapy (NAC) is the standard treatment for patients with locally advanced breast cancer, which was recently introduced for early stage disease to achieve breast preservation. Objectives: The aim of this study was to evaluate the rate of local recurrence, distant recurrence, breast cancer mortality, five years disease free survival (DFS) and five years overall survival (OS) in patients with breast cancer after NAC and to compare these factors with patients, who received adjuvant chemotherapy. Methods: In this cross sectional study, 188 patients with stage I to III breast cancer, who received NAC (group A), and 376 patients with breast cancer, who received adjuvant chemotherapy (group B), were selected and matched based on a time- stratified 2:1 approach between October 2002 and December 2014. Their clinical-pathological profile and survival study were compared. Results: The mean age of patients was 48.23 years in group A and 48.76 years in group B. The median follow-up time was 52 months. In group A and group B, 13.1% and 7.7% of the patients had local recurrence during the five years of follow up, respectively (P < 0.001). In group A and group B, five years PFS rate and five years OS rate was 66% and 70%, and 81.8% and 82.6%, respectively. According to log-rank test analysis, there was no significant difference between two groups as five years DFS and five years OS (P = 0.058 and P = 0.98, respectively). Conclusions: This study showed that higher frequency of local recurrence in NAC group than adjuvant chemotherapy group was not associated with any significant increase in distant recurrence or breast cancer mortality. Longer follow-up time of the patients to compare survival between two groups is recommended.

An infodemiology study on breast cancer in Iran

PurposeAccording to the studies conducted in Iran, the breast cancer is the most frequent type of cancer among women. This study aimed to explore the state of health information supply and demand on breast cancer among Iranian medical researchers and Iranian Web users from 2011 to 2015.Design/methodology/approachA mixed method research is conducted in this study. In qualitative part, a focus group interview is applied to the users to identify their selected keywords searched for breast cancer in Google. The collected data are analyzed using Open Code software. In quantitative part, data are synthesized using the R software in two parts. First, users’ internet information-seeking behavior (ISB) is analyzed using the Google Trends outputs from 2011 to 2015. Second, the scientific publication behavior of Iranian breast cancer specialists are surveyed using PubMed during the period of the study.FindingsThe results show that the search volume index of preferred keywords on breast cancer has increased from 4,119 in 2011 to 4,772 in 2015. Also, the findings reveal that Iranian scholars had 873 scientific papers on breast cancer in PubMed from 2011 to 2015. There was a significant and positive relationship between Iranian ISB in the Google Trends and SPB of Iranian scholars on breast cancer in PubMed.Research limitations/implicationsThis study investigates only the state of health information supply and demand in PubMed and Google Trends and not additional databases often used for medical studies and treatment.Originality/valueThis study provides a road map for health policymakers in Iran to direct the breast cancer studies.

Health-related quality of life of Iranian breast cancer patients: a meta-analysis and systematic review.

Quality of life is the most important psychological factor affecting breast cancer patients. This study aimed to examine the health relatedquality of life of breast cancer patients in Iran. International (PubMed, Web of science, Scopus and Google scholar) and national (SID, Magiran) databases were searched for related studies to September 2017. The quality of the articles was evaluated using the Hoy tool. Out of 232 initial studies, 18 studies performed on 2263 people were included in the final stage of the study. Based on the EORTC-QLQ-C30 and random effect method, the pooled mean score of quality of life in 1073 people was 57.88 (95% CI 48.26-67.41, I2 = 97.90%) and the pooled mean score of quality of life based on WHOQOL-BREF in 357 people was 66.79 (95% CI 45.96-87.62, I2 = 99.50%). According to the results of the study, a moderate level of quality of life in women with breast cancer was indicated. Therefore, the use of multidimensional approaches can improve their quality of life.

Effecst of Patho- Biological Factors on the Survival of Recurrent Breast Cancer Cases

Background:Recurrence of breast cancer after treatment is generally due to loco-regional invasion or distant metastasis. Although patients with metastasis are considered incurable, existing treatments might prolong a patient’s life while also improving its quality. Choice of approach for individual patients requires identification of relevant survival factors. This study concerns factors influencing survival after recurrence in Iranian breast cancer patients.Methods:This study was performed on 442 recurrent breast cancer patients referred to the Cancer Research Center of Shahid Beheshti University between 1985 and 2015. After confirming recurrence as a distant metastasis or loco-regional invasion, the effects of demographic, clinic-pathologic, biological, type of surgery and type of adjuvant treatment on survival were evaluated using univariate and multivariate stratified Cox models.Results:The mean survival after recurrence was 18 months (5 days to 13 years), 219 patients (70.42%) survived two years, 75 patients (24.12%) survived from 2 to 5 years, and 17 patients (5.47%) survived more than 5 years. In this study, it was found through univariate analysis that the factors of age, lymph node status, DFI, place of recurrence and nodal ratio demonstrated greatest influence on survival after recurrence. On multivariate analysis, the most important factors influencing survival were the place of recurrence and the lymph node status.Conclusion:The results of this study enhance our knowledge of effects of different factors on survival of patients after breast cancer recurrence. Thus, they may be used to inform treatment choice.

Predictors of Pathological Complete Response to Neoadjuvant Chemotherapy in Iranian Breast Cancer Patients

Background:Achievement of pathologic complete response (pCR) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is associated with both overall survival and disease-free survival. The aim of present study was to identify clinical and pathological factors associated with achieving pCR in Iranian breast cancer patients receiving NAC.Methods:A retrospective review of all breast cancer patients treated with neoadjuvant chemotherapy between April 2012 and September 2016 at our institution was performed; 207 cases were evaluable for analysis. pCR was defined as having no residual invasive tumor in the breast surgical specimen removed following neoadjuvant therapy.Results:In univariate analysis, factors associated with pCR were age less than 35 years (p = 0.03), absence of Lymphovascular invasion (LVI) (p = 0.002) and negative hormone receptor status (p = 0.003). Hormone receptor status (P = 0.01; OR, 2.45; CI, 1.20 - 4.99) and LVI (P = 0.001; OR, 0.22; CI, 0.10 - 0.46) remained predictive variables in multivariate analysis after correction for the other variables.Conclusions:In conclusion, the results of this study suggests that presence of Lymphovascular invasion and positive hormone receptor status are associated with poorer response to neoadjuvant chemotherapy in breast cancer patients.

Family Intervention Based on the FOCUS Program Effects on Cancer Coping in Iranian Breast Cancer Patients: a Randomized Control Trial

Background:Breast cancer affects patients’ lives. Many breast cancer patients have problems with coping and they need support from their families. Family involvement based on the FOCUS program is designed to support breast cancer survivors within their families. The aim of this study was to investigate the effect of family involvement based on the FOCUS program on coping in breast cancer patients undergoing chemotherapy in academic centers in Urmia in 2016.Methods:In this randomized controlled trial study, sixty breast cancer survivors were randomly assigned into intervention (N=30) and control (N=30) groups. The FOCUS program family-based intervention featured six sessions covering subject areas of family involvement, optimism, cancer coping, uncertainty reduction and symptom management. The instruments used were demographic and cancer coping questionnaires. Data were analyzed with SPSS 20 software.Result:The findings revealed a significant improvement in total cancer coping scores (t= -12/39, p<0.001), in all subscales including individual (t= -11/52, p<0.001), positive focus (t= -7/03, p<0.001), coping (t= -7/28, p<0.001), diversion (t= -11/76, p<0.001), planning (t=-4/91, p<0.001) and in interpersonal (t=-11/14, p<0.001). No significant changes were observed for the control group.conclusion:The results showed that family involvement based on the FOCUS program increases the ability to cope in breast cancer survivors.

Association of Elevated Peripheral Blood Micronucleus Frequency and Bmi-1 mRNA Expression with Metastasis in Iranian Breast Cancer Patients

Background:In order to find cytogenetic and molecular metastasis biomarkers detectable in peripheral blood the spontaneous genomic instability expressed as micronuclei and Bmi-1 expression in peripheral blood of breast cancer (BC) patients were studied in different stages of the disease compared with unaffected first-degree relatives (FDRs) and normal control.Methods:The Cytokinesis Block Micronuclei Cytome (CBMN cyt) and nested real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assays, were respectively used to measure genomic instability and Bmi-1 gene expression in 160 Iranian individuals comprised of BC patients in different stages of the disease, unaffected FDRs and normal control groups.Result:The frequency of micronuclei and Bmi-1 expression were dramatically higher in distant metastasis compared with non-metastatic BC. In spite of micronucleus frequency with no association with lymph node (LN) involvement and hormone receptor status, the Bmi-1 expression level was higher in LN positive and triple negative patients.Conclusion:Our results indicate that increased genomic instability expressed as micronuclei and higher Bmi-1 expression in peripheral blood are associated with metastasis in breast cancer. Therefore implementation of micronucleus assay and Bmi-1 expression analysis in blood as possible cytogenetic and molecular biomarkers in clinical level may potentially enhance the quality of management of patients with breast cancer.

Analysis of BRCA1/2 Mutations and Performance of Manchester Scoring System in High Risk Iranian Breast Cancer Patients: A Pilot Study

Background: Breast cancer is the most frequent malignancy in Iranian women. Pathogenic mutations in BRCA1 and BRCA2 genes account for 20% to 25% of familial breast cancer. BRCA1 and BRCA2 mutation frequencies differ considerably among various geographic regions and ethnicities. Most studies have primarily used Caucasian populations to delineate the population and family risks associated with germline BRCA1 and BRCA2 mutations, leaving patients of other ancestries understudied. As genetic testing for BRCA1 and BRCA2 mutations is underused in Iran, it is of great importance to be able to describe the mutation spectrum of these genes and subsequently the genetic risks and testing benefits particular to Iranian population. Methods: We designed a pilot study to identify the full spectrum of BRCA1 and BRCA2 sequence variations and large single or multi-exonic deletions in 20 Iranian breast cancer patients with a high likelihood of hereditary predisposition to breast cancer. Manchester score, as a validated scoring system for the probability of carrying a BRCA1/2 mutation, was calculated for all patients to determine the cut-off value for genetic testing in Iranian families. Results: Two pathogenic [c.4566C > G (p.Tyr1522Ter), c.1961delA (p.Lys654Serfs*47)] and one likely pathogenic (c.5153-26A > G) variants in BRCA1 and 2 pathogenic variants [c.8165C > G (p.Thr2722Arg), c.92G > A (p.Trp31Ter)] in BRCA2 gene were identified. Assuming a Manchester score of 20 points as cut-off value to perform BRCA genetic testing, this scoring system has a sensitivity of 80%, specificity of 60%, positive predictive value (PPV) of 40%, and negative predictive value (NPV) of 90%. Conclusions: Considering the high cost of testing in Iran, it seems that that the cut-off value of 20 points is more appropriate.