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Background: Survival after breast conserving surgery (BCS) vs. modified radical mastectomy (MRM) is a controversial issue. In this study, we want to compare the disease-free survival (DFS) of women who underwent BCS with those treated by MRM. Method: In this historical cohort study, a total of 1097 women who were diagnosed with breast cancer between 2001 and 2007 and received modified MRM or BCS were entered into the study and followed up to March 2017. Kaplan-Meier estimator and extended cox model, and Cox proportional hazards model with propensity score weighting were implemented to compare overall survival between two groups. Results: A total of 283 women with a maximum follow-up of 11.1 years and age 47.17 ± 11.278 were met the inclusion criteria. The results of the extended cox model did not show any difference between the survival of two groups (P = 0.35). After implementing the Cox model with propensity score weighting, the inferences remained unchanged (P = 0.67). Conclusion: The patients treated with BCS tend to have the same DFS rate as those who underwent a mastectomy in a randomized controlled trial-like setting using propensity score weighting. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most frequent cancer in Iranian females. Due to the changes in lifestyle and reproductive risk factors, the BC incidence rate has been rapidly increasing. Knowing risk factors of BC could significantly contribute to improve preventive behaviors. To investigate the relationship between menstrual and reproductive factors and BC in Iranian female population. Methods: Web of Science, PubMed, Scopus, and SID as well as references of included studies were searched. Among relevant published observational studies, 27 studies met the inclusion criteria. Pooled risk estimates for the risk factors were determined using random-effects models due to the presence of substantial heterogeneity (P < 0.05). Results: All of the selected studies had case-control design. There was a positive relationship between maternal age at first pregnancy and risk of BC (OR = 1.79 95% CI: 1.36-2.35). Also, menopausal status was associated with higher risk of BC (OR = 1.60 95% CI: 1.18-2.17), whereas, there was no association between menarche age and increased risk of BC (OR = 0.55 95% CI: 0.29-1.03). History of abortion (OR = 1.21 95% CI: 0.97-1.5), nulliparity (OR = 1.43 95% CI: 0.89-2.31), and breastfeeding history (OR = 0.68 95% CI: 0.42-1.09) were not associated with BC risk. Conclusions: Our findings suggest that age at the first pregnancy and menopausal status were significantly associated with BC risk among Iranian women, whereas menarche age, nulliparity, and history of breastfeeding were not. In regard to the history of abortion, our findings revealed no association with BC, but in high-quality studies, this relationship was significant. [ABSTRACT FROM AUTHOR]

Background: The impact of initiation time of radiotherapy after breast surgery on disease-free status of patient is a controversial issue. We assessed the relationship between the delay in adjuvant radiotherapy and surgery and relapse or metastasisfree survival in women with breast cancer taking heavy censoring into account. Method: This was a historical cohort study on 284 patients with breast cancer, who underwent surgery between 2001 and 2007 and followed up until March 2017. The association of the duration between radiotherapy and surgery, as well as other demographic and clinical factors with occurrence of local relapse or metastasis of breast cancer was examined through penalized Cox regression modeling. The obtained data were analyzed using R 3.6.3. Results: A total of 284 women with the mean age of 47.2 ± 11.3 years met the inclusion criteria. The maximum follow-up time was 11.1 years and the time between surgery and radiotherapy was 168 ± 84.3 days. About 10% of the patients experienced local relapse and 19% had metastasis. In multiple analysis of factors related to diseasefree survival, the stage of disease was significant, while surgery to radiotherapy interval (≤180 days vs >180 days) did not have any significant impact on hazard of failure. Analysis of 3, 4, or 5 months of delay in radiation therapy did not imply any significant affects. Conclusion: In the studied patients, the delay in radiotherapy initiation after surgery did not lead into outcomes of local relapse or metastasis. [ABSTRACT FROM AUTHOR]

Introduction: In various radiotherapy techniques for breast cancer, the inclusion of internal mammary nodes (IMNs) in the target volume is important for selecting the most appropriate technique. This study aimed to compare three radiotherapy techniques with the inclusion of IMNs regarding the dose homogeneity index (DHI) of regional lymph nodes and the chest wall, besides the dose received by the heart and the left lung. Material and Methods: Three radiotherapy techniques were planned for CT imaging of the RANDO phantom, including the wide tangent (WT); oblique parasternal photon (OPP); and oblique parasternal electron (OPE) techniques. The doses reaching the contoured organs were compared between the three techniques, using the data gathered from the thermoluminescent dosimetry and treatment planning system. Results: The OPE technique produced a lower absorbed dose for the left IMNs, compared to the other two techniques. In the OPP technique, the dose received by the left lung was higher than its tolerance, while the lung dose in the OPE technique was slightly lower than the WT technique. The absorbed dose by the heart was the lowest in the WT technique; also, the DHI value was better for this technique than the other two techniques. Conclusion: The WT technique showed better results regarding the dose homogeneity distribution of IMNs and the chest wall, as well as protection of organs at risk. [ABSTRACT FROM AUTHOR]

If there is unobserved heterogeneity among susceptible patients in competing risks cure models, applying the methods that do not consider this heterogeneity may lead to invalid results. Therefore, this study aimed to introduce a model to cover the above properties of survival studies. We introduced a unified model by combining a parametric mixture cure gamma frailty model and vertical modeling of competing risks. We obtained estimates of parameters by an iterative method and Laplace transform technique. Then, we calculated the cumulative incidence functions (CIFs) and related confidence bounds using a bootstrap approach. We conducted an extensive simulation study to evaluate the performance of the proposed model. The results of the simulation study showed the superior performance of our proposed competing risks cure frailty model. Finally, we applied the proposed method to analyze a real dataset of breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: There are believed to be several risk factors affecting the prognosis of breast cancer through their effect on the growth rate of tumour. In the present study, we investigated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and tumor protein P53 (TP53) as well-known biomarkers, particularly in breast cancer prognosis, associated with age. Method: In a case-control study, 406 breast cancer patients were considered retrospectively. In order to extract the clinical and pathologic data, we employed the patients' records. The extracted information was compared between two groups: for patients under 40 (group I) and above 40 years of age (group II). Herein, the researchers performed statistical analysis using SPSS Ver16. Results: The most prevalent type of cancer in both groups was found to be invasive ductal carcinoma. The major method of treatment was modified radical mastectomy. According to our observations, grade 3 breast cancer was more common in group I. Lymph node involvement significantly increased in group I, while oestrogen and progesterone receptor expressions were less in this group. HER2, TP53, and Ki-67 oncogenes were overexpressed in group I compared with group II. Conclusion: Expression of HER2, TP53, and Ki-67 biomarkers and a reduction in the number of hormonal receptors in younger patients (<40YO) indicated that breast cancer might be more invasive in younger women with breast cancer and therefore, they might have poorer prognosis and less favourable outcomes. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a preventable cancer with various risk factors. In this study, we assessed different risk factors involved in invasive cervical cancer in the Northeast of Iran. Methods: In a case-control study, 99 patients with advanced cervical cancer were compared to 102 healthy, normal women. Cervical cancer risk factors were documented for these groups using a questionnaire and available medical notes. Univariate analysis was done for each risk factor, followed by multivariate regression analysis, to evaluate the most powerful risk factors after adjustment. Results: Multivariate model indicated that sexual transmitted diseases (STD) [p<0.001; OR=7.88, 95% CI (2.59-23.93)], age at first intercourse =16 [p=0.048; OR=6.22, 95% CI (1.06-36.51)] and age [p=0.001; OR= 1.11, 95% CI (1.04-1.18)] were independently significant risk factors for cervical cancer. Conclusion: According to this survey, the significant influence of major risk factors, including STD, age at first intercourse, and age itself, has been underlined. Moreover, increasing the social knowledge and educating people to prevent highrisk sexual behaviors, HPV testing, and routine use of HPV vaccine, which is nowadays regarded as a preventive measure in cervical cancer, may also be needed to be implemented in our prevention program. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Muslim cancer patients and healthcare professionals face several challenges about the necessity of fasting and its possible side effects during the holy month of Ramadan. We aimed to study the prevalence of fasting among cancer patients during Ramadan and opinions of health care professionals about fasting among cancer patients in Iran. Methods: We conducted a cross-sectional survey during the Ramadan (July-August) in 2013. Participants were 620 cancer patients and, 187 healthcare professionals in several cancer clinics from different provinces of Iran. We used self-administered questionnaires and collected data from patients, and healthcare professionals to collect data. We performed descriptive analysis by using Stata statistical software. Results: Out of 620 patients who participated in this study, 428 (69%) were women. 76 (13%) of patients had fasted for at least a day during Ramadan and, from which 41 (7%) had fasted whole months because of their religious belief. Among patients who had refrained from fasting, the reasons were lack of sufficient physical strength (403, 65%), excessive thirst (141, 23%). 275 (44%) of participants had consulted with their physician about fasting. We found that more than 50% of physicians advised against fasting for patients following surgery, pre-operation, recent hospitalization, and consumption of oral or intravenous chemotherapy. Most of the healthcare professionals (68%) believed that cancer survivors could not fast even if they have no signs or symptoms or side-effects after the treatment. Conclusion: Although most of the cancer patients refrain from fasting, some cancer patients practice fasting and face challenges during the holy month of Ramadan in Iran. Most patients consult about fasting in Ramadan with their doctor who has variable opinions about this issue. Development of guidelines for healthcare professional and cancer patients regarding Ramadan fasting is needed. [ABSTRACT FROM AUTHOR]

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). Conclusions: The SNP309T>G polymorphism in MDM2 may not be associated with breast cancer in this Iranian population. [ABSTRACT FROM AUTHOR]

Air pollution consists of chemicals resulting from many human activities and natural resources, which can cause gene mutations. Almost, it is proven that air pollution contributes to lung cancer and its relationship with other cancers including bladder, cervical cancer, ovary, prostate, brain and breast cancer is suspected. Breast cancer is the most frequent cancer in women and the prominent cause of death among them all around the world. Poor prediction of risk factor leads to discovery of more reliable factors. Mammary tumors in animals that are generated by chemicals compounds, give possible mechanisms for effects of environmental pollutants. Therefore, the purpose of our study is to review the available literature for investigating the relation of ambient air pollution and breast cancer. Findings of our study highlight the possibility of increasing in occurrence of breast cancer, developing to invasive cancer and mortality in both premenopausal and postmenopausal women exposed to air pollution. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The etiology of breast cancer and our understanding on the carcinogenicity of different risk factors is impotant for control programms. We investigated the expression of estrogen and progesterone receptors (ER, PR), and human epithelial receptor 2 (HER2) overexpression and its associations, with environmental risk factors among breast cancer patients. Methods: We classified the patients into four groups including; triple negative (ER-/ PR-/HER2-), HER2-overexpression (ER-/PR-/HER2+), luminal A (ER+ and/or PR+/HER2-) and luminal B (ER+ and/or PR+/HER2+). We used a case-only design and multinomial logistic regression analyses. Results: In premenopausal patients, those with high BMI had lower prevalence of luminal B tumors compared to luminal A groups (OR= 0.42, 95% CI= 0.23 to 0.74). However, in the postmenopausal groups, prevalence of the luminal B tumors was less than luminal A tumors oral contraceptive pill (OCP) users (OR= 0.64, 95% CI= 0.42 to 0.98). In addition, among those who had an older age at menarche had a higher risk of ER2-overexpression tumors compared to luminal A tumors (OR= 2.82, 95% CI= 1.29-6.19). Conclusion: Expression of HER2, ER, and PR, among breast cancer patients seems to be associated with OCP use, BMI, age at menarche and age at first pregnancy. [ABSTRACT FROM AUTHOR]

Background: Women with the medical history of breast cancer constitute the biggest group of patients who survived cancer. Despite the high rate of mastectomy after breast cancer in Iran; only limited patients elect reconstruction surgery. The aim of our study was to evaluate the rate of tendency to breast reconstruction (BR) surgery among women with breast cancer who had mastectomy but not undergone reconstruction. Methods: This cross sectional study was conducted in Mashhad, north east of Iran during 2013. A total of 108 patients with mastectomy due to breast cancer were selected through convenience sampling and completed the questionnaire. Demographic data collected and 21 items of questionnaire were compared between patients with and without tendency to BR. Data were analyzed using Chi square, t tests and logistic regression. Results: In this study 62 (57.4%) patients had a tendency to BR and 46 (42.6%) had not. The mean (±SD) age of patients in first group was 43.3±8.03 and 49.6±9.9 in the second group (p<0.001). Frequency of agreement about impact of BR on appearance and beauty, mood, family living conditions and their opinion (p<0.001), lack of sufficient information (p=0.01), physician's opinion (p<0.001) and priority of cancer breast treatment (p=0.02) were significantly different between the two groups. Conclusion: More than half of the patients had a tendency to BR although they did not go under the surgery yet. Identification of factors that can increase the tendency and factors that help to change the intention to action are important and should be investigate in future research. [ABSTRACT FROM AUTHOR]

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 rsl0995190 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. [ABSTRACT FROM AUTHOR]

Objective: This study aims to determine the relationship between body size and body shape with the risk of breast cancer. Methods: In this case control study, 480 women participated (240 women with breast cancer in case group and 240 healthy women in control group). After completing the interview form, the weight, height, waist circumference, hip circumference and breast size, were measured. The data were analyzed using statistical test by SPSS11.5. Results: The present study showed that the mean of hip circumference were significantly different in both groups (p=0.036). The size of the breast was statistically significant between the two groups. Thyroid type, one of the body shapes, was more seen in the case group than control group (p<0.001). Conclusion: This study revealed that the risk of breast cancer increases with increased hip circumference. In addition, the results indicate that body shape may be a useful predictor in determining the risk of breast cancer. More studies should be designed to address this subject. [ABSTRACT FROM AUTHOR]

Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properties and invasive-phenotype has gained substantial attention, suggesting its role as an intriguing-target for cancer-therapy. In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement. However several important questions remain to be answered on the molecular mechanisms underlying the antitumor effects of crizotinib, as well as on its possible role in the treatment of different tumor types, including uppergastrointestinal- cancers. The aim of this review is to give an overview on critical role of the c-Met/HGF pathway in cancer, and the preclinical/clinical studies on c-Met inhibitors. There are accumulating evidences on therapeutic potential of c-Met inhibitors for the treatment of other malignancies, such as gastric and pancreatic cancers. However, further investigations are needed to identify determinants of the activity of c-Met inhibitors, through the analysis of genetic/ environmental alterations affecting c-Met and parallel pro-cancer pathways; mechanisms result in developing resistance to anti-c-Met agents; and selection of patients that might benefit from therapy. These studies will be essential to improve the selectivity/efficacy of future anticancer strategies of c-Met targeted-therapies in the treatment of upper gastrointestinal- cancers.

Purpose: The anti- estrogen drug, tamoxifen, is one of the most important medications used in the treatment of both advanced and localized breast cancer. However, such tamoxifen use may have some risks related to the endometrium and ovaries. We followed a group of women with breast cancer on tamoxifen for the development of ovarian cysts., Methods: Based on a cross sectional study, 35 pre and post menopausal patients with breast cancer on tamoxifen were followed by pelvic exam and vaginal ultrasonography for 3 cycles of 3 month intervals; occurrence and outcome of ovarian cysts were evaluated., Results: Of the 35 tamoxifen-treated patients enrolled in this study, 21 were postmenopausal and 14 were premenopausal. Their average age was 48.1+/-8.7 (range: 29-65 yrs) years. The mean duration of tamoxifen therapy was 30.5+/- 14 months (range: 12-60 months). Ovarian cysts were diagnosed in 12 (34.3%) patients, with surgery required in 6; pathological examination revealed malignancy in two cases., Conclusion: Development of ovarian cysts is a rather frequent event in women with breast cancer on tamoxifen. The majority of cysts are simple, which may resolve spontaneously or with discontinuation of tamoxifen, but malignancy needs to be ruled out.