Potential Role of Zinc Finger 365 rs10822013 and rs10995190 in Mammographic Density, Sporadic Breast Cancer Risk, and Prognosis.

Background: Despite suggesting many genetic risk markers as the outcome of Genome-wide association studies (GWAS) for breast cancer, replicating the results in different populations has remained the main issue. In this regard, this study assessed the association of two variations in Zinc Finger 365 (ZNF365) in an Iranian population. Methods: In a case-control study conducted at Mashhad University of Medical Sciences, Mashhad, Iran, between 2017 and 2020, ZNF365-rs10822013 and rs10995190 were genotyped using Allele-Specific PCR (AS-PCR). Breast density was assessed using mammography images. PHASE software module version 2 and SPSS version 16.0 were used for haplotype and statistical analyses. Quantitative and qualitative variables were compared between groups using independent t tests and Chi square tests, respectively. Binary logistic regression analysis was performed to calculate odds ratios. Multivariate analysis was then undertaken for the baseline variables, with a P<0.05 in the univariate analysis. The survival analysis was performed using the Kaplan-Meier method and the log-rank test. Results: In this survey, 732 females, including 342 breast cancer patients and 390 healthy subjects, were enrolled. rs10822013-T allele (P=0.014), rs10995190-G allele (P=0.003), and TG haplotype (P=0.002) were significantly associated with the increased risk of breast cancer. Moreover, rs10995190-GG genotype (P=0.042) and C-G haplotype (P=0.019) revealed a significant association with better overall survival. However, considered polymorphisms and their haplotypes indicated no association with breast density and clinical features of breast cancer. Conclusion: ZNF365 variants might be a potential risk marker of breast cancer in the Iranian population. The interaction between alleles in haplotypes may modulate the amount of the risk conferred by these variants. Further studies on different ethnic groups can validate these results.

Genetic contribution of caspase-8 variants and haplotypes to breast cancer risk and prognosis: a case-control study in Iran.

PURPOSE: Multiple genome-wide and candidate-gene association studies have been conducted to search for common risk variants of breast cancer. Recent large meta-analyses and consolidating evidence have highlighted the role of the caspase-8 gene in breast cancer pathogenesis. Therefore, this study aimed to identify common variations and haplotypes associated with risk and overall survival of breast cancer with respect to underlying susceptibility variants in the CASP8 gene region in a group of the Iranian population. METHODS: In a case-control study with a total of 1008 samples (455 cases and 553 controls), genotyping of 12 candidate polymorphisms, consisting of rs3834129, rs2037815, rs7608692, rs12990906, rs3769821, rs6435074, rs3754934, rs3817578, rs10931936, rs1045485, rs1045487, and rs13113, were performed using PCR-based methods, including ARMS-PCR, AS-PCR, RFLP-PCR, HRM-PCR, and TaqMan-PCR. RESULTS: rs3834129, rs3754934, rs12990906, and rs10931936 were associated with the risk and overall survival of breast cancer. Several haplotypes were also identified an associated with a higher risk of breast cancer, including a three-SNP haplotype rs3817578-rs10931936-rs1045485 [p < 0.001, OR = 1.78(1.32-2.41)]. rs3754934-C allele showed an association with a lower risk of death in all patients [p = 0.022; HR = 0.46(0.23-0.89)] and in the hormone-receptor-positive group [p = 0.038; HR = 0.37(0.14-0.95)], as well as CC genotype in the hormone-receptor-positive group [p = 0.002; HR = 0.09(0.02-0.43)]. CONCLUSION: The present study suggests a diagnostic and prognostic role of CASP8 gene variations in breast cancer. The risky haplotypes are likely to have one or more underlying breast cancer susceptibility alleles. Understanding the mode of action of these alleles will aid individual-level risk prediction. It also may help identify at-risk patients to provide them with better surveillance.

2q35-rs13387042 variant and the risk of breast cancer: a case-control study.

BACKGROUND: Breast Cancer is the most frequent neoplasm diagnosed among women worldwide. Genetic background and lifestyle/environment play a significant role in the disease etiology. According to Genome-wide association studies, some single-nucleotide polymorphisms such as 2q35-rs13387042-(G/A) have been introduced to be associated with breast cancer risk and features. In this study, we aimed to evaluate the association between this variant and the risk of breast cancer in a cohort of Iranian women. METHODS: Demographics and clinical information were collected by interview and using patients' medical records, respectively. DNA was extracted from 506 blood samples, including 184 patients and 322 controls, and genotyping was performed using allele specific-PCR. SPSS v16 was used for statistical analysis. RESULT: Statistically significant association was observed between AA genotype and disease risk in all patients [padj = 0.048; ORadj = 2.13, 95% CI (1.01-4.50)] and also ER-positive breast cancers [padj = 0.015; ORadj = 2.12, 95% CI (1.16-3.88)]. There was no association between rs13387042 and histopathological characteristics of the disease. Furthermore, overall survival was not statistically associated with genotype and allelic models even after adjustment for stage and receptor status (p > 0.05). CONCLUSION: There is a statistically significant association between 2q35-rs13387042 and breast cancer risk. rs13387042-AA genotype might be a risk-conferring factor for breast cancer development in the Iranian population. However, further consideration is suggested to confirm its role in risk assessment and probable association with other genetic markers.

Management of ovarian immature teratoma grade-II in pregnancy, two cases report and literature review.

Postoperative chemotherapy during pregnancy after first trimester is essential for patients with initial disease stage 1, grade 2 ovarian immature teratoma and it associates with lower disease progression and recurrence.

Evaluating the Association between CCR5delta32 Polymorphism (rs333) and the Risk of Breast Cancer in a Cohort of Iranian Population.

BACKGROUND: CC chemokine receptor 5 (CCR5) is introduced as an immune response modulator. The activity of CCR5 influences breast tumour development in a p53-dependent manner. This study aimed to investigate the frequency of CCR5delta32 and its association with the risk of breast cancer in 1038 blood samples in North East of Iran. METHODS: In this case-control study, we genotyped 570 control samples and 468 breast cancer patients by a gel electrophoresis-based gap-polymerase chain reaction (gap-PCR) method Mashhad, Iran. The data were analyzed using the SPSS software. RESULTS: Of 570 controls included, 542 (95.09%) had CCR5delta32 wild/wild (W/W) genotype, 28 samples (4.91%) had CCR5delta32 wild/deletion (W/D) genotype and none of them were CCR5delta32 deletion/deletion (D/D) genotype (0%). While 428 samples of patients (91.45%) had CCR5delta32 W/W genotype, 40 samples (8.55%) had CCR5delta32 W/D and CCR5delta32 D/D homozygous was nil (0%) amongst cases. All samples were in the Hardy-Weinberg equilibrium (P>0.05). According to the allele frequency, D allele, as a risky allele, in the cases was more than the control samples (0.0427 vs 0.0245, respectively) (P=0.0206). Hence, W/D genotype may confer a risk effect (OR=1.77, CI: 1.09-2.90; P=0.0206) compared with WW genotype between case and control groups. CONCLUSION: There is a statistically significant association between CCR5W/D and breast cancer risk. CCR5 may be regarded as a target for the prevention of breast cancer in certain conditions such as interaction with p53 variants, which remains to be further investigated.

The impact of CYP19A1 variants and haplotypes on breast cancer risk, clinicopathological features and prognosis.

BACKGROUND: Different genetic variants in hormone-regulating pathways have been identified to influence the risk of breast cancer. This study aimed to evaluate the association of CYP19A1 rs10046 and rs700519 polymorphisms with the risk, clinicopathological factors and prognosis of breast cancer. METHODS: In a case-control study, rs10046 and rs700519 polymorphisms were genotyped using ARMS-PCR and high-resolution melting (HRM), respectively, in a total of 702 females. Statistical analysis and evaluation of haplotypes and linkage disequilibrium were performed using SPSS v16, PHASE and 2LD. RESULTS: Although no association of rs700519 with breast cancer was observed, rs10046 in different genetic models as well as C-C/C-T and C-C/C-C diplotypes, revealed the association with the risk of breast cancer (p < 0.05). Moreover, the rs700519-C allele was shown to be associated with longer overall survival. In contrast, the T-T haplotype conferred s a shorter overall survival. rs700519-C allele was also significantly associated with menarche age. CONCLUSION: Based on the identified independent association between CYP19A1 diplotypes and rs700519-C allele with the risk and prognosis of the disease, the gene region and its genetic variants may have a diagnostic and prognostic role in breast cancer development. Further confirmation using other variants in this locus can validate these findings.

Spousal sexual life issues after gynecological cancer: a qualitative study.

PURPOSE: Sexual life is a multidimensional issue that can be affected negatively after gynecological cancer. The aim of this study was to reveal what sexuality life difficulties Iranian women with gynecological cancers experience. METHODS: A qualitative approach was conducted through face-to-face semi-structured interviews with 16 Iranian women with gynecological cancer and then analyzed with conventional content analysis. RESULTS: Three themes emerged from the data: (1) participant's struggle to maintain the sexual monopoly of the husband, (2) deterioration of intimacy, and (3) unpleasant bed-life experiences. Most women are ashamed to talk about their sexual relationships problems, and on the other hand, nurses and physicians ignore to talk about their sexual problems, so these women are alone in the face of this problem. CONCLUSION: Although women with gynecological cancer experience sexual problems such as reluctant to have sex and lack of enjoyment, they struggle to maintain sexual life with their husbands. These women do not have enough support. They believe that sexuality is a shameful issue, and they are reluctant to ask questions about it. Health professionals need to talk about the possibility of sexual problems due to changes in their bodies caused by cancer. These women need to be encouraged to talk about these problems, with consideration to their religious and cultural differences.

ESR1 gene variants, haplotypes and diplotypes may influence the risk of breast cancer and mammographic density.

Breast cancer as the most common cancer worldwide is influenced by genetic and physiological factors. Based on some evidence indicating the role of estrogen receptor 1 gene (ESR1) in breast cancer development, in this study, the association of three common variations in ESR1 gene with breast cancer and density in an Iranian population was evaluated. In a case-control study, 400 blood samples were collected for DNA extraction and genotyping. Breast density was assessed using mammography. ESR1 rs6915267 (G/A), rs2077647 (C/T) and rs1801132 (C/G) were genotyped using ARMS-PCR method. PHASE program was used to estimate the haplotypes frequencies. Our data analysis showed rs6915267 GA genotype in the heterozygous (GA) as well as co-dominant models was associated with lower mammographic density. None of the three variations were associated with the breast cancer risk. Haplotype analysis indicated G-T-C haplotype of rs6915267, rs2077647 and rs1801132 [OR = 0.54, 95% CI (0.31-0.92), p = 0.025] and G-T/G-T diplotype of rs6915267-rs2077647 [OR = 0.38, 95% CI (0.17-0.86), p = 0.019] were associated with a decreased risk of breast cancer. ESR1 may affect density of the breast and its haplotypes may modulate breast cancer risk.

Changes in Cytokeratin 18 during Neoadjuvant Chemotherapy of Breast Cancer: A Prospective Study.

BACKGROUND & OBJECTIVE: Prediction of response to neoadjuvant treatment is an important part of treatment of patients with breast cancer. This study aimed to assess changes in serum levels of Cytokeratin 18 during neoadjuvant chemotherapy in patients with locally advanced breast cancer and its association with neoadjuvant treatments. METHODS: This research was performed on newly diagnosed breast cancer patients referred to Omid Radiotherapy Center and radiotherapy and oncology departments of Emam Reza and Ghaem hospitals, in Mashhad, Iran. Serum levels of M30 and M65 fragments of Cytokeratin 18 were measured before and 24 hours after the first course of neoadjuvant chemotherapy. Changes in serum levels of Cytokeratin 18 and its fragments and their correlation with pathologic response were analyzed. RESULTS: Pre- and post-chemotherapy levels of M30 were respectively 223.9±18.94 and 250.7±23.92 U/L (P=0.24). For M65, these levels were respectively 301.5±313.9 and 330.2±352.2 U/L (P=0.1). Changes in M30 level during chemotherapy in patients with and without pathologic complete response were -20±92.69 and 43.1±106.5, respectively (P=0.1). For M65, these changes were respectively -247±55 and 76±240 (P=0.1). Baseline levels of M30 and M65 had no relation with menopausal status, tumor grade, hormone receptor status, Ki67 expression, molecular subtype, and stage. CONCLUSION: Our findings showed statistically insignificant changes in the level of Caspase-cleaved- (M30) and uncleaved- (M65) cytokeratin 18 fragments (apoptotic and necrotic indicators, respectively) during neoadjuvant chemotherapy in patients with breast cancer. There was no notable relationship between tumor-related factors and either baseline levels or serum changes of CK18 fragments. Also, there was no correlation between M30/M65 level and pathologic response to neoadjuvant chemotherapy.

A Case-Control Study on the p73 G4A Gene Polymorphism and Susceptibility to Breast Cancer in an Iranian Population.

BACKGROUND: The tumor protein p73 (TP73) is a homolog of TP53 family. Ectopic p73 overexpression largely mimics p53 activities as a tumor suppressor and activates the transcription of p53-responsive genes and as a result induce apoptosis. This study aimed to investigate the association between p73 G4A polymorphism and the risk of breast cancer in a northeastern Iranian population. METHODS: This case-control study was performed on 105 patients who admitted in educational hospitals of Mashhad University of Medical Sciences, Iran during 2013-2015, with breast cancer as case group and 120 healthy women as the control group. PCR-CTPP method was used to investigate the relationship between the p73 G4A polymorphism and the risk of breast cancer. RESULTS: There was no significant association between the AA genotype of the p73 G4A polymorphism and breast cancer in case and control groups. Although G allele frequency was higher in the case group, the abundance of this allele between case and control groups was not statistically meaningful and, as a result, not associated with the risk of breast cancer in this study group. CONCLUSION: There was no association between G4A p73 polymorphism and the risk of breast cancer in a northeastern Iranian population.

The relation between stressful life events and breast cancer: a systematic review and meta-analysis of cohort studies.

PURPOSE: Breast cancer is the most common cancer among women with high rate of mortality. This systematic review and meta-analysis was conducted to investigate the relation between stressful life events and breast cancer. METHODS: We searched PubMed, Scopus, ScienceDirect, and Google scholar databases from their inception until June 2018. The keywords and phrases we used in the search were (life events AND stress AND breast cancer OR neoplasm) to identify potentially relevant cohort studies that reported relative risk estimates and confidence intervals of this association. Pooled Risk ratio and 95% confidence intervals (CIs) were calculated using random effects model. RESULTS: Out of 168 potentially relevant publications, 11 documents met the inclusion criteria. The results showed that history of stressful life events slightly increases the risk of breast cancer [pooled Risk Ratio: 1.11 (95% CI 1.03 to 1.19)]. CONCLUSIONS: History of stressful life events could be associated with a moderate increase in the risk of breast cancer. We advise that receiving psychological and counseling services after occurrence of stressful life events of women should be taken seriously.

Oral administration of nanomicelle curcumin in the prevention of radiotherapy-induced mucositis in head and neck cancers.

Oral mucositis (OM) is a complication of head and neck cancer (HNC) therapy with negative impact on the quality of life. Although definitive treatment has not yet been established, there is interest towards the use of natural compounds owing to their few side effects. Curcumin has a variety of biological and pharmacological properties including anticancer and anti-inflammatory effects. AIM: The aim of this study is to evaluate the effect of curcumin in the form of nanomicelle on OM in HNC patients receiving radiotherapy. METHODS: In this clinical trial, 32 HNC patients were allocated to case and control groups, and respectively received nanocurcumin or placebo during radiotherapy. RESULTS: We found a statistically significant difference in the severity of mucositis between the 2 groups at all visits. In contrast to the control-group patients, who all developed OM in the 2nd week of radiotherapy, only 32% of the case group developed OM with no obvious oral or systemic side effects. CONCLUSION: Our data show that nanomicelle curcumin is an effective agent in the prevention of OM or reducing its severity. Thus, the administration of nanocurcumin can be considered as a reasonable approach to hinder the development of OM in HNC patients requiring radiotherapy.

Status of FAS and FAS Ligand Gene Polymorphisms in Patients with Breast Cancer in Northeastern IRAN.

BACKGROUND: The First apoptosis signal (FAS) and First apoptosis signal ligand (FASL) genes initiate the apoptosis pathway, playing a central role in the tumor growth and metastasis. Gene polymorphisms including -1377 G/A in the promoter region of FAS and -844 C/T in the promoter region of FASL have shown to change the transcription activities of these genes. METHODS: In this study we evaluated association of these polymorphisms with risk of metastasis of breast cancer, in a population selected from Mashhad, Iran. A total of 115 patients with breast cancer and 115 controls were recruited in this case-control study. Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP) was applied for genotyping on extracted DNA from participant's blood. Unconditional logistic regression was used to estimate cancer risk by calculating odds ratios (OR) and their 95% confidence intervals (95% CIs). RESULTS: There was no significant association between these genetic polymorphisms and breast cancer risk. Additionally, our results showed no significant influence from the above mentioned gene polymorphisms on metastasis of breast cancer. CONCLUSION: These results suggest that the FAS-1377G/A and FASL-844 C/T gene polymorphism don't have much influence on the susceptibility to metastasis of breast cancer in northeastern Iranian population. Therefore, we suggest to investigate impact of other candidate gene polymorphisms on metastasis of breast cancer for future research.

Lack of an Association between a Functional Polymorphism in the MDM2 Promoter and Breast Cancer in Women in Northeast Iran.

BACKGROUND: Breast cancer is one of the most common cancers among women worldwide. Tumor protein 53 (TP53) and its regulator, the mouse double murine 2 (MDM2) protein homologue, influence tumorigenesis through their key roles in cell division and response to DNA damage. The MDM2 SNP309T>G (rs2279744) polymorphism in the promoter region of the MDM2 can cause dysfunction and inactivation of TP53, which promotes tumor progression. The aim of this study was to investigate the possible association between this polymorphism and breast cancer in a northeastern Iranian population. METHODS: A case-control study with 128 female breast cancer patients and 143 healthy women was conducted. PCR-ARMS was performed to assess the MDM2 SNP309T>G (rs2279744) polymorphism. RESULTS: No significant association was found between the GG genotype or G allele polymorphisms and breast cancer in patients or controls (p = 0.116, OR [95% CI]: 1.267 [0.616, 2.603] and p= 0.143, OR [95% CI]: 1.326 [0.908, 1.935], respectively). For the G allele polymorphism, a significant difference of 8 years in the average cancer diagnosis age was observed between TT and TG carriers (40.57 vs. 48.15 years, respectively, p = 0.029). CONCLUSION: The SNP309T>G polymorphism in MDM2 may not be associated with breast cancer in this Iranian population.

Long-Term Disease-Free Survival of Non-Metastatic Breast Cancer Patients in Iran: A Survival Model with Competing Risks Taking Cure Fraction and Frailty into Account

Introduction: Survival modeling is a very important tool to detect risk factors and provide a basis for health care planning. However, cancer data may have properties leading to distorted results with routine methods. Therefore, this study aimed to cover specific factors (competing risk, cure fraction and heterogeneity) with a real dataset of Iranian breast cancer patients using a competing risk-cure-frailty model. Materials and methods: For this historical cohort study, information for 550 Iranian breast cancer patients who underwent surgery for tumor removal from 2001 to 2007 and were followed up to March 2017, was analyzed using R 3.2 software. Results: In contrast to T-stage and N-stage, hormone receptor status did not have any significant effect on the cure fraction (long-term disease-free survival). However, T-stage, N-stage and hormone receptor status all had a significant effect on short-term disease-free survival so that the hazard of loco-regional relapse or distant metastasis in cases positive for a hormone receptor was only 0.3 times that for their negative hormone receptor counterparts. The likelihood of locoregional relapse in the first quartile of follow up was nearly twice that of other quartiles. The least cumulative incidence of time to locoregional relapse was for cases with a positive hormone receptor, low N stage and low T stage. The effect of frailty term was significant in this study and a model with frailty appeared more appropriate than a model without, based on the Akaike information criterion (AIC); values for the frailty model and one without the frailty parameter were 1370.39 and 1381.46, respectively. Conclusions: The data from this study indicate ae necessity to consider competing risk, cure fraction and heterogeneity in survival modeling. The competing risk-cure-frailty model can cover complex situations with survival data.

Fluorescent in Situ Hybridization and Real-Time Quantitative Polymerase Chain Reaction to Evaluate HER-2/neu Status in Breast Cancer.

BACKGROUND: Breast cancer remains the most common and second lethal cancer in females. HER-2/neu is one of the most important amplified oncogene in breast cancer. The amplification of HER-2 is correlated with decreased survival, metastasis, and early recurrence. The amplification of HER-2/neu gene and synthesis of the protein are reported in 10%-34% of breast cancer cases associated with tumor size, advanced tumor stage, high-grade tumor, young age at diagnosis, absence of steroid hormone receptor, and lymph node involvement. METHODS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods are options to evaluate HER-2 expression. The current study aimed at identifying the correlation between FISH and real-time polymerase chain reaction (PCR) in measuring HER-2 expression. RESULTS: The study investigated the performance of the real-time PCR as measured against FISH method in IHC +2 borderline cases. In a total of 120 IHC 2+ samples, 58.3% were negative and 41.6% positive for HER-2 gene, confirmed by FISH as a gold standard method. The real-time PCR ratio was <1.8 for a majority (82.8%) of the tumor samples with unamplified HER-2 gene by FISH as a gold standard assay. CONCLUSION: Despite the fact that real-time PCR is a promising method to evaluate HER-2 over expression and a supplementary array to FISH, according to the results of the present study it cannot be utilized instead of gold standard techniques; therefore, additional studies should be carried out to appraise the value of this method to evaluate HER-2 over expression.

Anti-Heat Shock Protein-27 Antibody Levels in Women with Breast Cancer: Association with Disease Complications and Two-Year Disease-Free Survival

Background and Aim: Breast cancer is a major healthcare problem in women. There are many reports about up-regulation of Hsp27 in cancer tissues but less is known about the potential relationship between Hsp27 antibody levels and breast cancer complications. We here investigated concentrations of serum Hsp27 antigen and antibodies in subjects with and without breast cancer and assessed potential associations with two-year disease-free survival, histological grade and number of lymph nodes. Materials and Methods: Specifically, serum Hsp27 antigen and antibody levels from 97 patients with breast cancer, and 65 healthy controls were determined by enzyme-linkedimmunosorbent assays (ELISAs). Results: Serum Hsp27 and antibody levels were significantly (p<0.001) higher in patients with breast cancer compared to the control group, but no relationship were found with two-year disease free survival, histological grade or number of lymph nodes (p> 0.6, 0.2 and 0.9 respectively). Conclusions: Elevated levels of Hsp27 antibody occur in patients with women with breast cancer but do not appear to be associated with the presence of disease clinical complications.

The Results of Chemotherapy with Two Variants of Intravenous CMF in Patients with Early Stage Breast Carcinoma; Does Dose Density Matter?

No direct comparisons can be made in early stages of breast cancer, between the intravenous combinations of: cyclophosphamide, methotrexate, and fluorouracil; named modified versions of CMF with the classical oral version of CMF. Since these modifications have different dose intensities and densities, the outcomes for their subsequent treatments may be varied, and not produce the same results. Despite that, classical CMF has been commonly replaced with intravenous modifications. This study aimed to assess the results of treatment with two common intravenous modification of CMF chemotherapy; to represent the most effective and successful substitute of classical CMF. Five hundred patients in two groups were eligible to take part in the experiment. For two hundred and twenty-nine patients in the group CMF 1&8, chemotherapy was administered intravenously on days 1 and 8 every 28 days for six cycles consisting of: cyclophosphamide 600 mg/m2 , methotrexate 40 mg/m2 , fluorouracil 600 mg/m2 . In the group CMF 1 which consisted of 271 patients, chemotherapy was administered with all the same drugs and doses, however, it was only administered on day 1 and repeated at 21-day intervals for six cycles. Overall survival (OS), disease-free survival (DFS), the prognostic factors and other probable interventional factors were then compared between the two groups. The 5-year OS rate of 87.5% and 10-year OS rate of 82% in the group CMF 1&8 were statistically significantly better than 5-year OS of 84% and 10-year OS of 61.5% in the group CMF 1 (p = 0.01). The 5-year and 10-year DFS rates were 76% and 60% respectively, in the group CMF 1&8 compared with 77% and 54% respectively in the group CMF 1 (p = 0.8). Two groups were comparable regarding their distribution of different prognostic factors and other probable interventional factors. Considering 30% higher dose density of drugs in the protocol of CMF 1&8, the improving outcome can be related to the efficacy of dose-dense chemotherapy. Therefore, this intravenous modification is the better substitute of classical CMF.

Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial.

OBJECTIVE: The aim of this study is to evaluate the preventive effects of carvedilol on doxorubicin-induced cardiotoxicity. METHODS: In this trial, 70 female patients with breast cancer who were candidates to receive doxorubicin were enrolled, from which 30 were selected randomly to receive carvedilol 6.25 mg daily during chemotherapy, with the rest receiving placebo as the control group. Both groups were evaluated 1 week before and 1 week after chemotherapy by measuring the left ventricular ejection fraction and strain/strain rate. RESULTS: Data analysis showed that the case group presented no significant reduction in strain and strain-rate parameters after intervention, while there was a significant reduction in these parameters in the control group (all p values <0.001). Also, the mean differences of strain parameters in the case group were significantly less than in the control group in all evaluated heart walls (basal septal strain, p = 0.005, basal lateral strain, p = 0.001, basal inferior strain, p < 0.001, and basal anterior strain, p < 0.001); the same was true for the strain-rate parameters (the p values for basal septal, basal lateral, basal inferior and basal anterior strain rate were 0.037, 0.037, 0.002 and <0.001, respectively). CONCLUSION: This study shows that carvedilol can prevent doxorubicin-induced cardiotoxicity. Whether this prophylaxis should be considered as the preferred method needs further investigation.