The Relationship between VDR Gene Polymorphisms Bsm1 and Apa1 with Breast Cancer Risk.

Background In addition to its multifaceted physiological functions, vitamin D is recognized for its protective role against cancer. To manifest its effects, vitamin D engages with the vitamin D receptor ( VDR ) gene responsible for its encoding. Investigations have unveiled that polymorphisms within the VDR gene exert influence over the expression and/or functionality of the VDR protein. Notably, certain VDR gene polymorphisms have emerged as particularly pertinent in the context of tumorigenesis, including Fok1 (rs2228570), Bsm1 (rs1544410), Taq1 (rs771236), and Apa1 (rs7975232). This study aims to scrutinize the correlation between the Bsm1 and Apa1 polymorphisms and the susceptibility to breast cancer development. Materials and Methods In this study, 50 patients suffering from breast cancer with less than 6 months breast cancer diagnosis and 50 healthy control individuals have been chosen. Restriction fragment length polymorphism polymerase chain reaction was used to determine the genotype of polymorphisms. Results The results of the statistical analysis showed that among the studied polymorphisms, there was no correlation with the development of breast cancer. Conclusion Studies on various cancers have produced inconsistent results regarding vitamin D's role in the development and progression of cancer. Therefore, further research is necessary to determine vitamin D's role in cancer development and progression.

Comparative Evaluation of Captopril, Spironolactone, and Carvedilol Effect on Endothelial Function in Breast Cancer Women Undergoing Chemotherapy.

Background: Breast cancer is the most prevalent malignancy in females which needs chemotherapy treatment. Studies demonstrated that anti-cancer agents used for chemotherapy in cancer patient causes endothelium dysfunction. Several researches showed the efficacy of angiotensin-converting enzyme inhibitors, Carvedilol and Spironolactone on improving endothelial function. This study aimed to evaluate the effect of the combination of Spironolactone, Carvedilol, and Captopril on endothelial function in breast cancer patients. Materials and Methods: This study is a prospective Randomized Clinical Trial in breast cancer patients who underwent chemotherapy. Patients were divided into two groups who received the combination of Captopril, Spironolactone, and Carvedilol or standard regimen for 3 months during chemotherapy. Before and after intervention, ejection fraction (EF), E/A ratio and e' and flow-mediated dilation (FMD) properties were calculated and then compared. Results: Fifty-eight patients with a mean age of 47.57 ± 9.46 years were evaluated. The mean FMD after the intervention is statistically different in case and controls (<0.001). E/A ratio and e' are not statistically different between groups after intervention. The mean EF was not statistically different between the two groups after intervention. Conclusion: Prescribing combination of Carvedilol, Spironolactone, and Captopril in breast cancer patients undergoing chemotherapy can improve endothelial function and may have beneficial effects on diastolic function.

Diagnostic Value of Nonacid Nucleic Blood Tumor Marker Panels in Early Diagnosing Breast Cancer: A Systematic Review and Network Meta-Analysis.

This study is aimed at determining the best nonacid nucleic blood tumor marker panels in terms of sensitivity, specificity, and accuracy in order to detect breast cancer in early stages (I, II, and III) among eligible women for breast cancer screening. PubMed, Web of Science, Embase, Scopus, and Cochrane were systematically reviewed to assess nonacid nucleic blood tumor marker panels' diagnostic value in women, both healthy and patient (before any anticancer treatment), for detecting breast cancer. A network meta-analysis was carried out using a Bayesian network meta-analysis to estimate combined odd ratio (OR) and 95% CI credible interval for presenting the results. Rankograms plot was drawn to rank the diagnostic value of different panels. Of the 2358 titles initially identified, 9 studies and 8 panels were included in the network meta-analysis. Panels A (MMP-9/TIMP-1) and K (TF1+TF2+TF3) had the highest sensitivity in early stages, as panel A with OR = 11.61 and 95% CI (1.49-102.5) demonstrated a better function than mammography. Panels H (CA 15.3 + IL-18) and A (MMP-9/TIMP-1) had the highest specificity in early stages, but no significant difference with mammography. Panels A (MMP-9/TIMP-1) and H (CA 15.3 + IL-18) had the highest accuracy in early stages, as they significantly exhibited a higher function than mammography with OR = 6.87 and 95% CI (2.07-31.35) as well as OR = 3.44 and 95% CI (1.15-11.07), respectively. Panel A including MMP-9/TIMP-1 in early stages demonstrated a higher diagnostic value for breast cancer than the rest of the panels.

Identification and Subtyping of Cryptosporidium parvum and Cryptosporidium hominis in Cancer Patients, Isfahan Province, Central Iran.

Background: Cryptosporidium spp. are protozoan parasites that cause diarrhea in humans and animals. Subtyping data about Cryptosporidium spp. in Isfahan, Iran is limited; therefore, we aimed to study the prevalence rate of Cryptosporidium spp. in cancer patients, associated risk factors, and subtypes of Cryptosporidium spp. Methods: Fecal samples were collected from 187 cancer patients from the Oncology Department of Seyed-al-Shohada Hospital, Isfahan University of Medical Sciences during 2014-2020 and screened for Cryptosporidium spp. using microscopical techniques. Nested PCR amplifying 18S rRNA gene was used to detect Cryptosporidium spp. in samples, followed by subtyping using nested PCR amplifying gp60 sequences. Results: Overall, the rate of infection with Cryptosporidium spp. was 4.3% (n=8). Five samples out of eight samples were identified as Cryptosporidium spp. using a nested PCR for the 18S rRNA gene, two subtypes of C. parvum named IIaA18G3R1 (n = 2) and IIaA17G2R1 (n = 2), and one subtype of C. hominis named IbA6G3 were identified by sequencing of the gp60. The IbA6G3 subtype has rarely been detected in other investigations. Conclusion: This is the first survey on the subtyping of Cryptosporidium spp. in this region. The results of the present survey show both zoonotic and anthroponotic transmission routes in the region.

Application of Multi-State Model in Analyzing of Breast Cancer Data.

BACKGROUND: The multistate model is used generally to fit the longitudinal data. This model can determine the natural trend of disease progress in different states of treatment, recuperate, metastasis and finally death. We aimed to use multistate models in order to analyzing breast cancer (BC) data. STUDY DESIGN: A historical cohort study. METHODS: In this historical cohort study, 573 women with BC were studied. These patients were referred to Isfahan Sayed-o-Shohada Hospital during 1999-2006 and followed up to Apr 2017. The corresponding provided data were gathered by Isfahan Cancer Prevention Center. Then data analyzed by multistate models in R 3.4.1 software. RESULTS: The mean and standard deviation of women age were 47.19±10.77 years. The transition probability from state of first treatment to recuperate state was 71%, to metastasis state 2% and to death was 16%. The sojourn time in different states of disease was 2.39 yr for first treatment, 6.93 yr for recuperate and 0.16 yr for death. CONCLUSION: This model is able to predict the transition probabilities in different state of disease, so its results are useful for clinical researches. In addition, with transition probabilities and also survival mean in each state in hand, the physicians will be able to suggest suitable treatment plans for patients.

Plasma Level Of miR-21 And miR-451 In Primary And Recurrent Breast Cancer Patients.

PURPOSE: MiR-21 and miR-451 are closely associated with tumor initiation, drug resistance, and recurrence of breast cancer (BC). This study was conducted to evaluate the possible value of the plasma level of miR-21 and miR-451 as potential biomarkers for the detection of primary and recurrent BC. PATIENTS AND METHODS: In this descriptive-analytical study, the plasma level of miR-21 and miR-451 was measured in 23 primary BC patients, 24 recurrent (local/distant metastasis) BC patients, and 24 aged-match women as healthy controls using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, data were analyzed using SPSS software, and the area under the receiver operating characteristic (ROC) curve of miRNAs was measured. RESULTS: The plasma level of miR-21 was significantly increased in both groups of primary (P<0.001) and recurrent (P<0.001) BC patients in comparison with healthy women. However, the plasma level of miR-451 was not significantly changed in primary (P=0.065) and recurrent (P=0.06) BC patients than healthy controls. The elevation of both miR-21 and miR-451 plasma level was not significantly changed in recurrent patients compared with non-recurrent (primary) patients (P=0.481, and P=1, respectively). Based on the ROC analyses, the areas under the curves (AUC) for miR-21 in discriminating primary BC and recurrent BC patients from healthy controls were 0.828 (95% CI: 0.712 to 0.944) and 0.865 (95% CI: 0.756 to 0.974), respectively. CONCLUSION: These data indicating that plasma miR-21 may be useful as a biomarker for the detection of both primary and recurrent BC. However, plasma miR-451 lacks enough sensitivity in the detection of primary and recurrent BC, and more studies are needed in this area.

Clinical Trial: CYP2D6 Related Dose Escalation of Tamoxifen in Breast Cancer Patients With Iranian Ethnic Background Resulted in Increased Concentrations of Tamoxifen and Its Metabolites.

Introduction: The polymorphic enzyme cytochrome P450 2D6 (CYP2D6) catalyzes a major step in the bioactivation of tamoxifen. Genotyping of clinically relevant CYP2D6 alleles and subsequent dose adjustment is a promising approach to individualize breast cancer therapy. The aim of this study was to investigate the relationship between the plasma levels of tamoxifen and its metabolites and different CYP2D6 genotypes under standard (20 mg/day) and dose-adjusted therapy (Registration ID in Iranian Registry of Clinical Trials: IRCT2015082323734N1). Materials and Methods: Using TaqMan® assays common alleles of CYP2D6 (∗1, ∗2, ∗4, ∗5, ∗6, ∗10, ∗17, and ∗41) and gene duplication were identified in 134 breast cancer patients. Based on CYP2D6 genotypes patients with an activity score 1 (n = 15) and 0-0.5 (n = 2) were treated with tamoxifen adjusted dosage of 30 and 40 mg/day, respectively. The concentration of tamoxifen and its metabolites before and after 4 and 8 months of dose adjustment were measured using LC-MS/MS technology. Results: At baseline, (Z)-endoxifen plasma concentrations (33 ± 15.5, 28.1 ± 14, 26.6 ± 23.4, 14.3 ± 8.6, and 10.7 ± 5.5 nmol/l for EM/EM, EM/IM, EM/PM, IM/IM and PM/PM, respectively) and the metabolic ratio (Z)-Endoxifen/N-desmethyltamoxifen (0.0558 ± 0.02, 0.0396 ± 0.0111, 0.0332 ± 0.0222, 0.0149 ± 0.0026, and 0.0169 ± 0.0177 for EM/EM, EM/IM, EM/PM, IM/IM, and PM/PM, respectively) correlated with CYP2D6 genotype (Kruskal-Wallis p = 0.013 and p < 0.0001, respectively). Dose escalation to 30 and 40 mg/day in patients with a CYP2D6 activity score of 1 (n = 15) and 0-0.5 (n = 2) resulted in a significant increase in (Z)-endoxifen plasma levels (22.17 ± 24.42, 34.43 ± 26.54, and 35.77 ± 28.89 nmol/l at baseline, after 4 and 8 months, respectively, Friedman p = 0.0388) along with the plasma concentrations of tamoxifen and its other metabolites. No severe side effects were recorded during dose escalation. Conclusion: For the first time, we show the feasibility of dose escalation of tamoxifen in breast cancer patients with compromised CYP2D6 activity and Iranian ethnic background to increase the plasma concentrations of (Z)-endoxifen.

GJA4/Connexin 37 Mutations Correlate with Secondary Lymphedema Following Surgery in Breast Cancer Patients.

Lymphedema is a condition resulting from mutations in various genes essential for lymphatic development and function, which leads to obstruction of the lymphatic system. Secondary lymphedema is a progressive and incurable condition, most often manifesting after surgery for breast cancer. Although its causation appears complex, various lines of evidence indicate that genetic predisposition may play a role. Previous studies show that mutations in connexin 47 are associated with secondary lymphedema. We have tested the hypothesis that connexin 37 gene mutations in humans are associated with secondary lymphedema following breast cancer surgery. A total of 2211 breast cancer patients were screened and tested for reference single nucleotide polymorphisms (SNPs) of the GJA4 gene (gap junction protein alpha 4 gene). The results presented in this paper indicate that two SNPs in the 3' UTR (the three prime untranslated region) of the GJA4 gene are associated with an increased risk of secondary lymphedema in patients undergoing breast cancer treatment. Our results provide evidence of a novel genetic biomarker for assessing the predisposition to secondary lymphedema in human breast cancer patients. Testing for the condition-associated alleles described here could assist and inform treatment and post-operative care plans of breast cancer patients, with potentially positive outcomes for the management of disease progression.

Information-sharing challenges between adolescents with cancer, their parents and health care providers: a qualitative study.

PURPOSE: We aimed to assess the viewpoints, experiences, and preferences within the clinical communication triangle (parent, adolescent, health care team) concerning the information-sharing process for adolescents with cancer. METHODS: This is a qualitative descriptive-exploratory study. Overall, 33 participants were recruited (adolescents diagnosed with cancer aged 15-20 years, their parents, oncologists, and nurses). In-depth semi-structured interviews were conducted and data were analyzed using constant comparative analysis. RESULTS: Data analysis yielded three main themes. Disaffiliation of adolescents in information-sharing process with three subthemes: confusion and unanswered questions; and, seeking information from inferior sources. Barriers to information-sharing with three subthemes: parents as gatekeepers in the information-sharing process, cultural background creating strong barriers for information-sharing, and the negative attitude of the medical team towards information-sharing. The last theme is cornerstones in information-sharing process with three subthemes: trust and honesty to enhance communication between adolescents and the medical team, the necessity of paving the way for information-sharing, and the value of gradual information-sharing based on the adolescents need and mental readiness. CONCLUSION: Participants believed that information-sharing was insufficient and provided recommendations for facilitating this process. Information-sharing process needs to be gradual and based on the adolescent's need and mental capacity. Future research needs to focus on devising a protocol for information-sharing with adolescents with cancer that accounts for familial and cultural factors, is carefully timed, and provides clearer and more efficacious communication between parents, adolescents, and the health care team.

Breaking bad news protocol for cancer disclosure: an Iranian version.

In Iran, as in many Asian and Middle Eastern countries, a significant proportion of cancer patients are never informed of their illness. One solution that has been proposed to tackle this challenge is to develop a localized protocol on cancer diagnosis disclosure based on the culture and values of community members, and train healthcare team members to deliver the bad news using this protocol. This article introduces a localized protocol for disclosure of bad news to cancer patients in Iran. This protocol consists of six steps, including assessment, planning, preparation, disclosure, support and conclusion. In the drafting of this protocol an attempt was made to meticulously consider the cultural features of the Iranian society. Although breaking bad news will never be easy, having an appropriate plan of action based on individual's attitudes, considerably helps health-care professionals, and provides more satisfaction in patients.

Effectiveness of trastuzumab as adjuvant therapy in patients with early stage breast cancer: A systematic review and meta-analysis.

Background: Trastuzumab in combination with chemotherapy has long been established as a standard treatment for HER2-positive patients in early stage breast cancer (BC). The present study aimed at assessing the effectiveness of trastuzumab adjuvant therapy in early stage BC in overall survival (OS) and disease-free survival (DFS). Methods: A systematic review and meta-analysis was performed to evaluate the effectiveness of trastuzumab adjuvant therapy. PubMed, Cochrane library, Scopus, Web of Science, and Embase databases were searched for relevant RCTs from the beginning to February 2017. Quality assessment of studies was conducted using the Cochrane Risk of Bias Tool. The desired outcomes were OS and DFS. Results: A total of 1818 articles were identified first, however, only 11 studies were eligible to be included in this study. Our findings and meta-analysis results revealed that trastuzumab is effective in increasing OS (OS hazard ratio: -0.286 ± 0.049, 95%CI (-0.381, - 0.191)) and improving DFS (DFS hazard ratio: -0.419± 0.077, 95%CI (-0.569, -0.269)). The most serious but negligible side effect of trastuzumab is congestive heart failure. Conclusion: Adding trastuzumab as adjuvant therapy in early stages of BC in HER2 positive patients could increase OS and DFS of the patients effectively.

A Hybrid Computer-aided-diagnosis System for Prediction of Breast Cancer Recurrence (HPBCR) Using Optimized Ensemble Learning.

Cancer is a collection of diseases that involves growing abnormal cells with the potential to invade or spread to the body. Breast cancer is the second leading cause of cancer death among women. A method for 5-year breast cancer recurrence prediction is presented in this manuscript. Clinicopathologic characteristics of 579 breast cancer patients (recurrence prevalence of 19.3%) were analyzed and discriminative features were selected using statistical feature selection methods. They were further refined by Particle Swarm Optimization (PSO) as the inputs of the classification system with ensemble learning (Bagged Decision Tree: BDT). The proper combination of selected categorical features and also the weight (importance) of the selected interval-measurement-scale features were identified by the PSO algorithm. The performance of HPBCR (hybrid predictor of breast cancer recurrence) was assessed using the holdout and 4-fold cross-validation. Three other classifiers namely as supported vector machines, DT, and multilayer perceptron neural network were used for comparison. The selected features were diagnosis age, tumor size, lymph node involvement ratio, number of involved axillary lymph nodes, progesterone receptor expression, having hormone therapy and type of surgery. The minimum sensitivity, specificity, precision and accuracy of HPBCR were 77%, 93%, 95% and 85%, respectively in the entire cross-validation folds and the hold-out test fold. HPBCR outperformed the other tested classifiers. It showed excellent agreement with the gold standard (i.e. the oncologist opinion after blood tumor marker and imaging tests, and tissue biopsy). This algorithm is thus a promising online tool for the prediction of breast cancer recurrence.

Alterations in the echocardiographic variables of the right ventricle in asymptomatic patients with breast cancer during anthracycline chemotherapy.

BACKGROUND: Anthracycline-induced cardiotoxicity can reach an irreversible phase; therefore great efforts are made to diagnose it early. As the right ventricle (RV) is smaller than the left, the right side of the heart is probably influenced by anthracycline to a greater extent and in a shorter time. The purpose of the present study was to investigate the early effects of chemotherapy on the right side of the heart. METHODS: This cross-sectional study was performed in Isfahan University hospitals from August 2014 to December 2015. Subjects were 67 patients with breast cancer who were planned to receive anthracycline for the first time. Echocardiography was performed before administration of anthracycline and 6 months later. Variables included right heart measures (RV end-diastolic dimensions, right atrium length and diameter), RV fractional area change (RVFAC), index of myocardial performance (Tei index), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure, lateral tricuspid annular early and late diastolic velocities, and tissue Doppler diastolic and systolic velocities. RESULTS: Forty-nine of the subjects completed the study. RV end-diastolic diameters and Tei index (0.31 to 0.37) were significantly increased (p<0.001). RVFAC (49.83% to 43.59%) and TAPSE (18.8 to 17.7 mm) were significantly decreased (p<0.001). There was a significant reduction in E (57.06 to 46.59 cm/s, p<0.001), E/A ratio (1.42 to 1.18, p<0.001), E' (16.73 to 12.4 cm/s, p<0.001), E'/A' ratio (1.21 to 0.9, p<0.001) and S' (12.59 to 10.57 cm/s, p<0.001). Systolic pulmonary arterial pressure (20.63 to 22.24 mm Hg, p=0.04) was significantly increased. CONCLUSIONS: This study shows a significant decrease in RV systolic and diastolic function during chemotherapy for 6 months. These reductions are in the normal range and can probably be considered an early indicator of anthracycline-induced cardiotoxicity.

Bevacizumab plus FOLFOX or FOLFIRI regimens on patients with unresectable liver-only metastases of metastatic colorectal cancer.

BACKGROUND: The present study was aimed to evaluate the efficacy and safety of at least three cycles of Bevacizumab in combination with chemotherapy regimens, FOLFIRI or FOLFOX to treat liver metastatic colorectal cancer and improved response rates in these patients. MATERIALS AND METHODS: In this non-randomized clinical trial, 38 patients were enrolled and followed for 12-weeks period of chemotherapy. Fifteen patients under treated with FOLOFX (Group I), 15 patients under treated with FOLOFIRI (Group II), 4 patients under treated with FOLOFX + Bevacizumab (Group III), and 34 patients under treated with FOLOFIRI + Bevacizumab (Group IV). Response to treatment was assessed in all patients as main endpoint. Patients in groups I and II, who did not response to treatment after 12 weeks of chemotherapy, were followed by groups III and IV regimens, respectively, for 12 weeks. RESULTS: Overall response rate was 35% (19 of 54), and complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) rates in all patients were 18%, 17%, 35%, and 30%. PR, SD, and PD were different among groups, but no statistical significance was noted among groups (P-value >0.05). No patient achieved a CR in groups III and IV, although CR was observed in 4 patients (27%) and 6 patients (40%) in groups I and II, respectively. The rare of CR was statistically significant among studied groups (P-value = 0.013). CONCLUSION: Results showed that adding Bevacizumab to chemotherapy regimens, in patients who did not response to FOLFIRI or FOLFOX regimen, did not increase CR in these patients.

Genomic rearrangement screening of the BRCA1 from seventy Iranian high-risk breast cancer families.

BACKGROUND: The second leading cause of cancer deaths in women is breast cancer. Germline mutations in susceptibility breast cancer gene BRCA1 increase the lifetime risk of breast cancer. Eighty-one large genomic rearrangements (LGRs) have been reported up to date in BRCA1 gene, and evaluation of these rearrangements helps with precise risk assessment in high-risk individuals. In this study, we have investigated LGRs in BRCA1 among Iranian high-risk breast cancer families. MATERIALS AND METHODS: Seventy patients with breast cancer who were identified negative for point mutations or small deletions/insertions of BRCA1 gene were selected. Deletions and duplications of BRCA1 gene were evaluated using multiplex ligation-dependent probe amplification (MLPA). RESULTS: Two deletions, deletion of exons 1A/1B-2 and exon 24, were detected in two patients with breast cancer. The former alteration was found in a woman with a strong family history of breast cancer while the latter one was detected in a woman with early onset of breast cancer. CONCLUSION: Although our data confirm that LGRs in BRCA1 comprise a relatively small proportion of mutations in hereditary breast cancer in the Iranian population, MLPA analysis might be considered for screening of LGRs in high-risk individuals. It is worth to note that our results are consistent with previous studies in various Asian and European countries.

Effect of supplements: Probiotics and probiotic plus honey on blood cell counts and serum IgA in patients receiving pelvic radiotherapy.

BACKGROUND: Radiotherapy is frequently used in treatment approaches of pelvic malignancies. Nevertheless, it has some known systemic effects on blood cells and the immune system that possibly results in their susceptibility to infection. Probiotics are live microbial food ingredients that provide a health advantage to the consumer. Honey has prebiotic properties. The aim of this clinical trial was to investigate probable effects of probiotic or probiotics plus honey on blood cell counts and serum IgA levels in patients receiving pelvic radiotherapy. MATERIALS AND METHODS: Sixty-seven adult patients with pelvic cancer were enrolled. Patients were randomized to receive either: (1) Probiotic capsules (including: Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium breve, Bifidobacterium longum, and Streptococcus thermophiles) (n = 22), (2) probiotic capsules plus honey (n = 21) or (3) placebo capsules (n = 24) all for 6 weeks. Blood and serum samples were collected for one week before radiotherapy and 24-72 h after the end of radiotherapy. RESULTS: White blood cells (WBC), red blood cells (RBC), platelet counts, and serum IgA level were not significantly changed in patients taking probiotic (alone or plus honey) during pelvic radiotherapy. The mean decrease in RBC count was 0.52, 0.18, and 0.23 × 10(6) cells/µL, WBC count was 2.3, 1.21, and 1.34 × 10(3) cells/µL and platelet count was, 57.6, 53.3, and 66.35 × 10(3) cells/µL for the probiotic, probiotic plus honey, and placebo groups, respectively. The mean decrease of serum IgA was 22.53, 29.94, and 40.73 mg/dL for the probiotic, probiotic plus honey, and placebo groups, respectively. CONCLUSION: The observed nonsignificant effect of probiotics may be in favor of local effects of this product in the gut rather than systemic effects, however, as a trend toward a benefit was indicated, further studies are necessary in order to extract effects of probiotics or probiotic plus honey on hematologic and immunologic parameters in patients receiving pelvic radiotherapy.

The Performance of the Nottingham Prognosis Index and the Adjuvant Online Decision Making Tool for Prognosis in Early-stage Breast Cancer Patients.

BACKGROUND: Prognostic tools are widely used in the practice of Oncology and have been developed to help stratify patients into specific risk-related grouping. We sought to apply of two such tools used for patients with early-stage breast cancer and to correlate them with actual outcomes. METHODS: A retrospective study was designed to include early-stage breast cancer cases seen from 1994 to 2014 at the Seyedoshohada Hospital in Isfahan, Iran. Information was derived from the patients' records, and indices were derived from prognostic tools. Information was analyzed using descriptive statistics and one sample t-test. RESULTS: In 233 patients, the difference between the predicted overall survival (OS) by the Adjuvant Online (AO) prognosis tools (69.28) and the observed OS (71.2) was not statistically significant (P = 0.52), and the AO prognosis tools had predicted the patients' OS correctly. In the Nottingham prognosis index (NPI), this difference in all groups except the very poor prognosis group was not statistically significant. CONCLUSIONS: Adjuvant Online prognosis tools were capable of predicting the 10-year OS rate although not in all of the subgroups. The NPI was capable of distinguishing good, moderate, and poor survival rates, but this ability was not visible in more specific groups with moderate and poor prognosis.

Specific TaqMan allelic discrimination assay for rs1477196 and rs9939609 single nucleotide polymorphisms of FTO gene demonstrated that there is no association between these SNPs and risk of breast cancer in Iranian women.

BACKGROUND: Breast cancer (BC), is the most common cancer in women, that is the major cause of cancer-related morbidity and mortality in women. Obesity is considered as a major risk factor for BC that increases both the rate and intensity of the disease. Polymorphisms in FTO gene, a known obesity related gene, is shown to be associated with obesity-related traits as well. The aim of this study was to evaluate the association between previously reported single nucleotide polymorphisms (SNPs) of intron 1of FTO gene, rs1477196 and rs9939609 and risk of BC in a subset of Iranian BC patients. MATERIALS AND METHODS: We genotyped 99 cases and 100 controls for the two SNPs of rs9939609 and rs1477196 by TaqMan allelic discrimination assay. For each sample in an allelic discrimination assay, a unique pair of fluorescent dye probe is used. One fluorescent dye probe has a perfect match with the wild type allele and the other fluorescent dye probe is perfectly matched to the mutated allele. RESULTS: Our research has shown that the observed differences between case and control groups in the studied SNPs of FTO gene are not statistically significant (P > 0.05). CONCLUSIONS: Our findings suggest that there is no association between rs9939609 and rs1477196 polymorphisms in FTO gene and increase in risk of BC in the studied Iranian population. These results were inconsistent with that of previously reported case-control studies with BC that means presence of these polymorphisms depends on ethnic group.

The expression of CK-19 gene in circulating tumor cells of blood samples of metastatic breast cancer women.

Breast cancer is the most common cancer in women worldwide. Breast cancer in one third of all patients will go on to metastasis, which is the main cause of mortality in cancer cases. Tumor cells detach from primary tumor and enter into the circulation as circulating tumor cells (CTCs) which can form metastatic lesions. In this study, the expression of CK-19 gene in blood samples of metastatic breast cancer women was investigated and compared to control group. Twenty one patients with metastatic breast cancer and 20 healthy female volunteers enrolled in this study. For every patient and healthy donor 10 ml peripheral blood was collected. Peripheral blood mononuclear cells were isolated by gradient density centrifugation using Ficoll Hypaque. CK-19 gene expression was evaluated using SYBR green-based real-time quantitative polymerase chain reaction assays. The relative expression level of CK-19 was calculated using the 2(-ΔΔCt) analysis method. The mean of CK-19 expression was increased in metastatic breast cancer when compared to those of normal women (1.50 fold). 38.1% of the metastatic breast cancer patients showed CK-19 mRNA-detectable CTCs in their blood samples. There was no statistically significant difference between the relative expression level of CK-19 and the patient's clinicopathological characteristics. According to our knowledge, no study for determining CTC biomarkers in Iranian breast cancer women patients has yet been established. Our results suggest that the CK-19 mRNA expression investigation may be useful for monitoring CTCs in the blood of metastatic breast cancer patients, predicting early metastatic relapse or monitoring of anti-metastasis treatments.

Exploring factors related to metastasis free survival in breast cancer patients using Bayesian cure models.

BACKGROUND: Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. MATERIALS AND METHODS: Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. RESULTS: The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. CONCLUSIONS: Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.