Publications by authors named "Nahid Nafissi"

26 Publications

  • Page 1 of 1

Outcome of hypofractionated breast irradiation and intraoperative electron boost in early breast cancer: A randomized non-inferiority clinical trial.

Cancer Rep (Hoboken) 2021 Apr 1:e1376. Epub 2021 Apr 1.

Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.

Background: Intraoperative electron radiotherapy (IOERT) followed by hypofractionated whole breast irradiation (HWBI) provides the shortest possible time of adjuvant breast irradiation. The efficacy of either method has been described in previous reports; however, to our knowledge, the efficacy of combined therapy has not been reported.

Aim: To compare the toxicity and cosmetic outcome of IOERT as a tumor bed boost followed by HWBI with conventional whole breast irradiation (CWBI) followed by external electron tumor bed boost (EETBB) after breast conserving surgery (BCS) in patients with invasive breast cancer.

Methods: In 2019, a prospective noninferiority trial (IRCT20180919041070N2) was started. After BCS, early-stage breast cancer patients were treated by IOERT (10 Gy) and HWBI (42.56 Gy in 16 fractions) or CWBI (50 Gy in 25 fraction) and EETBB (10 Gy in 5) in a double-arm design. Acute/late toxicity and cosmetic outcome were evaluated by common toxicity criteria (CTC) after 1-year follow-up (FUP) at the level of p < .05.

Results: Of 60 eligible patients, 30 were allocated to each group. Regarding acute effects after a median FUP of 12 months, CTC-score of grade II-III erythema (p = .001) and desquamation (p = .005) were significantly higher in CWBI+EETBB compared to IOERT+ HWBI. However, there were no significant differences at the end of radiotherapy and after 1 month, 6 months, and 1 year. Cosmetic outcome after radiation was similar in both groups mostly rating as good/excellent after 1-year FUP.

Conclusions: Boost-IOERT/HWBI regimen has comparable acute and late treatment toxicity profiles compared to the CWBI.
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http://dx.doi.org/10.1002/cnr2.1376DOI Listing
April 2021

Comparison of the appendicitis inflammatory response and Alvarado scoring systems in the diagnosis of acute appendicitis in children.

J Med Life 2021 Jan-Mar;14(1):75-80

Department of Surgery, Hazrat-e Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.

Our objective was to compare the diagnostic accuracy of Alvarado and appendicitis inflammatory response (AIR) scoring systems among children suspected of acute appendicitis concerning their postoperative outcomes. During a two-year period, a prospective multicentric study was carried in the selected hospitals of Iran. All children who were admitted with the diagnosis of acute appendicitis were enrolled in the study. However, patients suffering from generalized peritonitis or those who had a history of abdominal surgery were excluded. Before decision-making, each patient's score according to two appendicitis scoring systems was calculated. The clinical outcomes and diagnosis of patients were then compared to the results of each scoring system. For those patients who were a candidate for surgery, the final diagnosis of acute appendicitis was made by histopathology. Patients were divided into a high- and low-risk group according to scoring systems outcomes. Among the patients with a low score for appendicitis, the AIR scoring system had a sensitivity and specificity of 95% and 74%, respectively, which was more promising in comparison to that of the Alvarado system (90% and 70%, respectively). Regarding the patients at higher risk of acute appendicitis, none of the scoring systems provided reliable results since both systems showed sensitivity and specificity of less than 50%, which was not sufficient to distinguish patients who are a candidate for surgery. AIR and Alvarado scoring systems are not accurate models to predict the risk of acute appendicitis among children; however, the AIR system could be used as a reliable material to rule out the acute appendicitis diagnosis.
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http://dx.doi.org/10.25122/jml-2020-0031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982267PMC
April 2021

Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations.

Breast 2021 Feb 26;57:25-35. Epub 2021 Feb 26.

G.RE.T.A. Group for Reconstructive and Therapeutic Advancements, Milan, Naples, Catania, Italy.

Introduction: The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice.

Methods: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach.

Results: According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence).

Discussion: This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients' values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.
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http://dx.doi.org/10.1016/j.breast.2021.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970134PMC
February 2021

A methylation signature at the CpG island promoter of estrogen receptor beta (ER-β) in breasts of women may be an early footmark of lack of breastfeeding and nulliparity.

Pathol Res Pract 2021 Feb 28;218:153328. Epub 2020 Dec 28.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Although little is known regarding the mechanisms behind the onset of breast cancer (BC) through reproductive risk factors, new researches have highlighted some early tumor-related methylation footmarks in the breast tissue of apparently clinically healthy women as their potential epigenetic mechanism. Previous evidence supports that the estrogen receptor beta (ER-β), whose anti-cancer roles had already been revealed in BC, is downregulated in the breasts of healthy nulliparous women. Nevertheless, data on such a link about its methylation alterations have not been reported. The goal of current study was to determine possible methylation alterations at CpG island promoter of the ER-β gene, including promoter 0 N and exon 0 N, in relation to aspects of reproductive history in the healthy breasts. The DNA was extracted from the breasts of 120 subjects undergoing cosmetic mammoplasty. Thereafter, the methylation levels of targeted regions in ER-β gene were determined by using MeDIP-qPCR assay. The results revealed that ER-β exon 0 N had no methylation in 84.2 % of the women, whereas the rest, comprising 2.5 % and 13.3 % of the samples, showed a lower and higher of its methylation, respectively. Interestingly, nulliparous women were found to have an elevated methylation level of the ER-β exon 0 N than parous women (P = 0.036). Moreover, we observed a high methylation of the ER-β exon 0 N in the breasts of non-breastfeeding women compared to breastfeeding subgroup (P = 0.048). Likewise, the non-breastfeeding subgroup showed exon 0N high methylation in comparison to women with breastfeeding >24 months (P = 0.023). Finally, although we found that 6.67 % of the samples had a high methylation level at the promoter 0N, no any relationship was found between its methylation and reproductive history. These results may provide key clues to revealing the epigenetic mechanism through which the nulliparity and lack of breastfeeding influencing the risk factor of BC as well as introducing the potential new early prediction and prevention strategies. Although further investigations need to be done in order to gain a better understanding the roles of these epigenetic signatures.
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http://dx.doi.org/10.1016/j.prp.2020.153328DOI Listing
February 2021

The Impact of the COVID-19 Pandemic on Surgical Management of Breast Cancer: Global Trends and Future Perspectives.

Oncologist 2021 01 25;26(1):e66-e77. Epub 2020 Nov 25.

Group for Reconstructive and Therapeutic Advancements (G.Re.T.A.), Milan, Naples, Catania, Italy.

Introduction: The rapid spread of COVID-19 across the globe is forcing surgical oncologists to change their daily practice. We sought to evaluate how breast surgeons are adapting their surgical activity to limit viral spread and spare hospital resources.

Methods: A panel of 12 breast surgeons from the most affected regions of the world convened a virtual meeting on April 7, 2020, to discuss the changes in their local surgical practice during the COVID-19 pandemic. Similarly, a Web-based poll based was created to evaluate changes in surgical practice among breast surgeons from several countries.

Results: The virtual meeting showed that distinct countries and regions were experiencing different phases of the pandemic. Surgical priority was given to patients with aggressive disease not candidate for primary systemic therapy, those with progressive disease under neoadjuvant systemic therapy, and patients who have finished neoadjuvant therapy. One hundred breast surgeons filled out the poll. The trend showed reductions in operating room schedules, indications for surgery, and consultations, with an increasingly restrictive approach to elective surgery with worsening of the pandemic.

Conclusion: The COVID-19 emergency should not compromise treatment of a potentially lethal disease such as breast cancer. Our results reveal that physicians are instinctively reluctant to abandon conventional standards of care when possible. However, as the situation deteriorates, alternative strategies of de-escalation are being adopted.

Implications For Practice: This study aimed to characterize how the COVID-19 pandemic is affecting breast cancer surgery and which strategies are being adopted to cope with the situation.
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http://dx.doi.org/10.1002/onco.13560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675306PMC
January 2021

Breast intraoperative electron radiotherapy: Image-based setup verification and in-vivo dosimetry.

Phys Med 2019 Apr 24;60:37-43. Epub 2019 Mar 24.

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Shohadaye Tajrrish Hospital, Tajrish Sq., P.O. 19996 14414, Tehran, Iran.

Introduction: Single fraction nature of intraoperative radiotherapy highly demands a quality assurance procedure to qualify both beam setup and treatment delivery. The aim of this study is to evaluate the treatment setup during breast intraoperative electron radiotherapy (IOERT) and in-vivo dose delivery verification.

Materials And Methods: Twenty-five breast cancer patients were enrolled and setup verification for each case was performed using C-arm imaging. The received dose by surface and distal end of target was measured by EBT2 film. The significance level of difference between obtained dosimetry results and predicted ones was evaluated by the T statistical test.

Results: Acquired C-arm images in two different oblique views revealed any misalignment between the applicator and shielding disk. The mean difference between the measured surface dose and expected one was 1.8% ± 1.2 (p = 0.983) while a great disagreement, 11.1% ± 1.5 (p < 0.001), was observed between the measured distal end dose and expected one. This discrepancy is mainly correlated to the backscattering effect from the shielding disk. Target depth nonuniformities can also contribute to this remarkable difference.

Conclusion: Employing the intraoperative imaging for IOERT setup verification can considerably improve the treatment quality. Therefore, it is suggested to implement this imaging procedure as a part of treatment quality assurance. Favorable agreement between the predicted and measured surface doses demonstrates the applicability of EBT2 film for dose delivery verification. The results of in-vivo dosimetry showed that the electron backscattering from employed shielding disk can affect the received dose by the distal end of tumor bed.
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http://dx.doi.org/10.1016/j.ejmp.2019.03.017DOI Listing
April 2019

Methylation of progesterone receptor isoform A promoter in normal breast tissue: An epigenetic link between early age at menarche and risk of breast cancer?

J Cell Biochem 2019 08 28;120(8):12393-12401. Epub 2019 Feb 28.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Emerging evidence indicates that some altered patterns of methylation that occur in breast tumors may also be found in breast tissue of healthy women in relation to the breast cancer (BC) risk factors. Progesterone receptor (PR) isoform α is a crucial regulator of breast hormone responsiveness and its hypermethylation plays an important role in the initiation and development of breast tumors. However, such a methylation change in healthy women and its link with the different risk factors has not yet been investigated. In the present study, we aimed to examine the relationship of possible methylation changes within a critical region in the promoter CpG island of PGR-α (progesterone receptor α) gene in the healthy women with a set of reproductive and nonreproductive BC risk factors. The breast tissues were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. The genomic DNA was extracted from the breast tissues and the methylation level of PGR-α promoter CpG island was determined by using MeDIP-qPCR assay. Using regression analysis, we found that increasing menarche age is inversely associated with the high methylation of PGR-α promoter ( β = -0.790, SE = 0.362; P = 0.031). Although lactating women had more methylation than nonlactating women (P = 0.026, the t test), this result was not confirmed by regression models. Such an observation may be helpful in better understanding of the underlying mechanisms by which early age at menarche increases the risk of BC. However, this perspective requires further validations in larger studies of more subjects as well as the inclusion of other related genes.
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http://dx.doi.org/10.1002/jcb.28505DOI Listing
August 2019

Comparison of the effects of stellate ganglion block and paroxetine on hot flashes and sleep disturbance in breast cancer survivors.

Cancer Manag Res 2018 26;10:4831-4837. Epub 2018 Oct 26.

Pain Research Center, Iran University of Medical Sciences, Tehran, Iran,

Background: The incidence of menopausal symptoms, including hot flashes and sleep disturbance, caused by drug treatment is a common problem in breast cancer survivors. Considering the limitations of hormone therapy in such patients, several studies have been conducted to find alternative methods. The aim of this study was to investigate and compare the effectiveness of stellate ganglion block (SGB) with that of paroxetine, which was approved by the US Food and Drug Administration (FDA) as a medicine for the treatment of hot flashes and ensuing sleep disturbance.

Patients And Methods: A total of 40 patients survived from breast cancer and complaining of these symptoms were equally assigned to two groups of 20 each. In the study group, SGB was performed successfully under sonography guidance using 10 mL of 0.5% bupivacaine, and in the control group (paroxetine), the daily administration of 7.5 mg of paroxetine was conducted for 6 weeks. The frequency and severity of hot flash attacks and sleep quality of patients were evaluated prior to the intervention and after 2, 4 and 6 weeks. The incidence of adverse events during treatment or follow-up was recorded.

Results: A significant decrease in hot flash score and sleep disturbance index (SDI) was observed in both groups. Comparison of the results showed no noticeable difference between the two groups. Two participants in the control group had discontinued medication due to gastrointestinal symptoms, and only one case of mild headache was reported in the study group.

Conclusion: SGB is as much effective as paroxetine in controlling hot flashes and sleep disturbances in breast cancer survivors and is associated with few complications.
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http://dx.doi.org/10.2147/CMAR.S173511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208490PMC
October 2018

Molecular prevalence of human papillomavirus infection among Iranian women with breast cancer.

Breast Dis 2018 ;37(4):207-213

Department of Virology, Iran University of Medical Sciences, Tehran, Iran.

Background: The etiology and molecular mechanisms involved in the development of breast cancer still remain poorly understood. Some epidemiological studies have shown an association between human papillomavirus (HPV) and breast cancer. However, the findings are controversial.

Objective: Our study was aimed to investigate the presence of HPV DNA in breast carcinomas of Iranian women.

Methods: In total, 72 samples of formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer collected between December 2014 and April 2016 were examined. HPV DNA detection was performed by nested-PCR assay. Next, positive samples were subjected to genotyping by the CLART HPV2 microarray system. All statistical analysis was carried out using SPSS v.18.0.

Results: HPV DNA was detected in 4/72 (5.55%) samples. Clinical factors were not statistically associated with HPV presence. However, CLART HPV2 microarray assay failed to determine the genotype of any positive samples.

Conclusion: The low frequency of HPV detected in our study does not support an association between breast carcinoma and HPV infection. However, it is possible that HPV may be responsible for breast carcinogenesis only in small percentage of all breast cancer.
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http://dx.doi.org/10.3233/BD-180333DOI Listing
April 2019

Early Parity Epigenetic Footprint of FOXA1 Gene Body in Normal Breast Tissue of Iranian Women

Iran Biomed J 2019 03 28;23(2):99-106. Epub 2018 Jul 28.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Young age at first full-term pregnancy (FFTP) is an important factor in breast cancer risk reduction. It is postulated that this protective effect is the result of stable molecular signatures imprinted by physiological process of pregnancy, but the molecular mechanism of this protective role is unclear. The aim of the current study was to identify the effect of early FFTP on methylation status of FOXA1 gene body. FOXA1 is an essential transcription factor for mammary gland development and estrogen responsiveness of breast tissue.

Methods: Fresh frozen normal breast tissues (n = 51) were collected from Iranian women who underwent cosmetic mammoplasty (27 nulliparous women and 24 parous women who have experienced first pregnancy before the age of 25). DNA was extracted and then methylated DNA immunoprecipitation (MeDIP) real-time PCR was used to assess FOXA1 gene body methylation.

Results: Our results revealed that FOXA1 methylation level is significantly higher in early parous compared with nulliparous group (p = 0.041).

Conclusion: Our study provides new hint about the association between early FFTP and epigenetic modifications within gene body of FOXA1 in normal breast tissue. More investigation is required for clarifying molecular mechanisms underlying this association in order to develop breast cancer prevention strategies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707108PMC
March 2019

Relationships between Reproductive Risk Factors for Breast Cancer and Tumor Molecular Subtypes

Asian Pac J Cancer Prev 2018 Jul 27;19(7):1767-1770. Epub 2018 Jul 27.

Department of Breast Surgery, Iran University of Medical Science, Rasool-Akram Hospital, Tehran, Iran. Email:

Background: Due to wide clinical differences in the various pathological types of breast cancer and also close associations between disease prognosis and molecular subtypes, relationships of the latter with traditional risk factors have been suggested. Hence, the present study aimed to assess any associations. Methods: This bi-center cross-sectional study was performed on 800 consecutive women with known breast cancer referred to two Comprehensive Cancer Centers in Tehran between 2006 and 2016. Baseline information related to reproductive risk profiles as well as pathological tumor diagnosis and molecular subtypes determined using immunohistochemical analysis by immune-staining for ER, PR, and HER2 molecules were collected by reviewing hospital records. Results: Of 800 samples included for immunohistochemical analysis, 314 (39.3%) were diagnosed as of Luminal A subtype, 107 (13.4%) as Luminal B subtype, 153 (19.1%) as HER-2 over-expressing, and 226 (28.3%) as triple negative. Among all reproductive risk factors initially assessed, young age was associated with HER-2 over-expression, greater tumor size and a history of abortion with the luminal B subtype, lower age at pregnancy with the luminal A subtype, and lower gravidity and a shorter duration of breastfeeding with the triple negative subtype. Conclusion: Each molecular subtype of breast cancer in our population may be associated with specific reproductive risk factors.
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http://dx.doi.org/10.22034/APJCP.2018.19.7.1767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165646PMC
July 2018

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

Asian Pac J Cancer Prev 2018 04 25;19(4):949-953. Epub 2018 Apr 25.

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Email:

Background: Recurrence of breast cancer after treatment is generally due to loco-regional invasion or distant metastasis. Although patients with metastasis are considered incurable, existing treatments might prolong a patient’s life while also improving its quality. Choice of approach for individual patients requires identification of relevant survival factors. This study concerns factors influencing survival after recurrence in Iranian breast cancer patients. Methods: This study was performed on 442 recurrent breast cancer patients referred to the Cancer Research Center of Shahid Beheshti University between 1985 and 2015. After confirming recurrence as a distant metastasis or loco-regional invasion, the effects of demographic, clinic-pathologic, biological, type of surgery and type of adjuvant treatment on survival were evaluated using univariate and multivariate stratified Cox models. Results: The mean survival after recurrence was 18 months (5 days to 13 years), 219 patients (70.42%) survived two years, 75 patients (24.12%) survived from 2 to 5 years, and 17 patients (5.47%) survived more than 5 years. In this study, it was found through univariate analysis that the factors of age, lymph node status, DFI, place of recurrence and nodal ratio demonstrated greatest influence on survival after recurrence. On multivariate analysis, the most important factors influencing survival were the place of recurrence and the lymph node status. Conclusion: The results of this study enhance our knowledge of effects of different factors on survival of patients after breast cancer recurrence. Thus, they may be used to inform treatment choice.
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http://dx.doi.org/10.22034/APJCP.2018.19.4.949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031793PMC
April 2018

Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors?

Genet Test Mol Biomarkers 2017 Aug 14;21(8):464-470. Epub 2017 Jul 14.

1 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran .

Background: Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis.

Materials And Methods: Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay.

Results: The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m (p ≤ 0.001) was higher than in the subgroups of women of BMI <25 kg/m (p < 0.001) and BMI 25-29 kg/m (p < 0.001) and was also higher in postmenopausal women compared with that in premenopausal women (p = 0.046). Pearson correlation coefficient analyses also showed that the high methylation of the ESR1 promoter was correlated with increasing age (r = -0.246, p = 0.007) and BMI (r = -0.331, p ≤ 0.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the ESR1 gene promoter and increased BMI (β = -0.285, 95% CI = -0.457 to -0.113, p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was found in the BMI ≥ 30 kg/m subgroup compared to the BMI 25-29 kg/m subgroup (p = 0.023).

Conclusion: These findings provide new hints about the relationship between epigenetic changes within the ESR1 gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor.
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http://dx.doi.org/10.1089/gtmb.2017.0028DOI Listing
August 2017

FBLN-4 and BCRP genes as two prognostic markers are downregulated in breast cancer tissue.

Cancer Biomark 2017 ;19(1):51-55

Department of Clinical Genetic, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Background: Fibulin-4 (FBLN-4) is an extracellular glycoprotein that is upregulated in some cancer and is khown as prognostic marker in ovarian and cervical cancer. Breast cancer resistance protein (BCRP) is an ATP-binding cassette transporter that facilitates the efflux of various anticancer drugs from the cell and cause MDR phenotype in breast tumors. Many studies are available that indicat overexpression of BCRP gene in breast cancer.

Objective: In the present study we aimed to analyze the expression level of FBLN-4 and BCRP in Iranian breast cancer patients.

Methods: We collected 40 samples of breast cancer and normal tissue from Tehran Khatam-al-Anbia hospital. To analyze the gene expression by using Real Time RT-PCR FBLN-4 and BCRP gene expression level were measured and then the association of gene expression with breast cancer were determined.

Results: Surprisingly the expression level of FBLN-4 and BCRP genes were downregulated in tumor tissues compared to adjacent normal tissues. Comparison of the gene expression and clinico-pathology reports indicate FBLN-4 gene expression was associated with breast cancer histological grade. We found no correlation between the expressions of BCRP gene with any clinico-pathological characters.

Conclusion: Interestingly and in contrast with our expectation, we found that the expression level of FBLN-4 and BCRP were downregulated in tumor compared to adjacent normal tissues. FBLN-4 was associated with grade histology and therefore can be considered as a potential prognostic biomarker.
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http://dx.doi.org/10.3233/CBM-160335DOI Listing
February 2018

Simultaneous ATM/BRCA1/RAD51 expression variations associated with prognostic factors in Iranian sporadic breast cancer patients.

Breast Cancer 2017 Jul 5;24(4):624-634. Epub 2017 Jan 5.

Department of Medical Genetic, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Background: DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues. Moreover, this study evaluates potential correlations among expression levels of these genes.

Methods: 50 breast cancer tissues were collected and examined for BRCA1, RAD51 and ATM gene expression by Real Time PCR. Expression changes were analyzed with REST software version 2009.

Results: mRNA expression was reduced in all these three genes when compared with β-Actin as a control gene (P  < 0.001). Spearman's test demonstrated a significant positive correlation among ATM, BRCA1 and RAD51 gene down expression (P  < 0.0001). There was a significant association between down expression of ATM with stage (P  < 0.05), necrosis (P  < 0.05), perineural invasion (P  < 0.05), vascular invasion (P  < 0.01), malignancy (P  ≤ 0.001), PR (P  < 0.05) and ER status (P  < 0.01). In addition, there was a significant association between down expression of BRCA1 with Ki67 (P  ≤ 0.001). Moreover, there was a significant association between down expression of RAD51 with lymph node involvement (P  < 0.01), auxiliary lymph node metastasis (P  = 0.01), age (P = 0.001), grade (P  < 0.05) and PR status (P  < 0.05).

Conclusion: This study suggests association between expression changes in several DSB repair genes in a common functional pathway in breast cancer and the significant association between abnormal expression of these genes and important clinical prognostic factors.
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http://dx.doi.org/10.1007/s12282-016-0750-zDOI Listing
July 2017

Gene expression profiling of the 8q22-24 position in human breast cancer: , , and genes are implicated in oncogenesis, while and genes may predict a risk of metastasis.

Oncol Lett 2016 Nov 30;12(5):3845-3855. Epub 2016 Sep 30.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; Molecular Diagnostic Laboratory, Genomic Research Center, Shahid Beheshti University of Medical Sciences, Ayatollah Taleghani Educational Hospital, Tehran 1985717413, Iran.

Gene expression profiling has been suggested to predict breast cancer outcome. The prognostic value of the 8q22-24 position in breast cancer remains to be elucidated. The present study evaluated expression patterns of the genes located at this position in metastatic and non-metastatic breast cancer. A total of 85 patients with recurrent/metastatic (n=15) and non-metastatic (n=70) early-stage, estrogen receptor-positive and lymph node-negative breast tumors were included. In addition, 15 normal breast tissue samples were used as controls. Demographic and clinical features were recorded. Subsequently, mRNA copy numbers of exostosin glycosyltransferase 1 (), WNT1 inducible signaling pathway protein 1 (), ATPase family, AAA domain containing 2 (), TSP-like 5 (), metadherin () and cyclin E2 () genes were measured by reverse transcription-quantitative polymerase chain reaction assay. The expression of and exhibited a significant decline in the metastatic breast cancer group compared to the control (P=0.015 and P=0.012, respectively). The expression of , and was significantly decreased in the metastatic (P=0.002, P=0.018 and P=0.016, respectively) and non-metastatic (P=0.038, P=0.045 and P=0.000, respectively) breast cancer groups compared with the control. The expression of in the metastatic and non-metastatic breast cancer groups was significantly increased compared with the control (P=0.002 and P=0.001, respectively). expression demonstrated a correlation with patient age and tumor size, and expression was correlated with lymphovascular invasion. None of the genes investigated exhibited any correlation with stage and grade of disease. The , , and genes may be implicated in the pathogenesis of human breast cancer, while the and genes may have the potential to serve as promising indicators of the risk of metastasis. However, further studies are required to validate these results.
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http://dx.doi.org/10.3892/ol.2016.5218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104179PMC
November 2016

Breast Cancer Survival Analysis Based on Immunohistochemistry Subtypes (ER/PR/HER2): a Retrospective Cohort Study.

Arch Iran Med 2016 Oct;19(10):680-686

Department of Epidemiology, School of Public Health, hamadan University of Medical Sciences, Hamadan, Iran.

Background: We conducted this study to estimate the prevalence of biomarkers, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) among patients with breast cancer and to explore their effects on disease mortality.

Methods: We conducted this registry-based retrospective cohort study in Tehran, in 2014, using the data on 1622 patients with breast cancer, diagnosed pathologically and registered with the Comprehensive Cancer Control Center from 1998 to 2013. The outcome of interest was the survival probability of patients with breast cancer based on receptor status along with other prognostic factors such as age, histopathology, stage/grade of tumor, metastatic status, and surgical procedures using the life table, Kaplan-Meier curves, and multivariate Cox proportional hazard model. We generated different subtypes based on expression of ER, PR, and HER2, positive (+) and/or negative (-).

Results: ER+/PR+/HER2- subtype (51.5%) was the most common form of breast cancer cells. Compared to the ER+/PR+/HER- subtype, the hazard ratio (95% confidence interval) of cancer mortality was 2.14 (1.13, 4.03) for ER-/PR-/HER2- subtype, 1.92 (1.03, 3.59) for ER-/PR-/HER2+ subtype and 5.19 (1.51, 17.86) for ER-/PR+/HER2+ subtype.

Conclusion: In this study, breast cancer cases with ER-/HER2+ tumors had shorter survival than those with ER+/PR+/HER2- tumors. Triple negative tumors were the only other subtype with a statistically significant poorer prognosis. The results of this study in a middle-income country further indicate the importance of receptor status, in particular HER2 status, in the prognosis of breast cancer.
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http://dx.doi.org/0161910/AIM.003DOI Listing
October 2016

Survival Analysis of Patients with Breast Cancer using Weibull Parametric Model.

Asian Pac J Cancer Prev 2015 ;16(18):8567-71

Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail :

Background: The Cox model is known as one of the most frequently-used methods for analyzing survival data. However, in some situations parametric methods may provide better estimates. In this study, a Weibull parametric model was employed to assess possible prognostic factors that may affect the survival of patients with breast cancer.

Materials And Methods: We studied 438 patients with breast cancer who visited and were treated at the Cancer Research Center in Shahid Beheshti University of Medical Sciences during 1992 to 2012; the patients were followed up until October 2014. Patients or family members were contacted via telephone calls to confirm whether they were still alive. Clinical, pathological, and biological variables as potential prognostic factors were entered in univariate and multivariate analyses. The log-rank test and the Weibull parametric model with a forward approach, respectively, were used for univariate and multivariate analyses. All analyses were performed using STATA version 11. A P-value lower than 0.05 was defined as significant.

Results: On univariate analysis, age at diagnosis, level of education, type of surgery, lymph node status, tumor size, stage, histologic grade, estrogen receptor, progesterone receptor, and lymphovascular invasion had a statistically significant effect on survival time. On multivariate analysis, lymph node status, stage, histologic grade, and lymphovascular invasion were statistically significant. The one-year overall survival rate was 98%.

Conclusions: Based on these data and using Weibull parametric model with a forward approach, we found out that patients with lymphovascular invasion were at 2.13 times greater risk of death due to breast cancer.
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http://dx.doi.org/10.7314/apjcp.2015.16.18.8567DOI Listing
October 2016

Application of a Non-Mixture Cure Rate Model for Analyzing Survival of Patients with Breast Cancer.

Asian Pac J Cancer Prev 2015 ;16(16):7359-63

Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail :

Background: As a result of significant progress made in treatment of many types of cancers during the last few decades, there have been an increased number of patients who do not experience mortality. We refer to these observations as cure or immune and models for survival data which include cure fraction are known as cure rate models or long-term survival models.

Materials And Methods: In this study we used the data collected from 438 female patients with breast cancer registered in the Cancer Research Center in Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients had been diagnosed from 1992 to 2012 and were followed up until October 2014. We had to exclude some because of incomplete information. Phone calls were made to confirm whether the patients were still alive or not. Deaths due to breast cancer were regarded as failure. To identify clinical, pathological, and biological characteristics of patients that might have had an effect on survival of the patients we used a non-mixture cure rate model; in addition, a Weibull distribution was proposed for the survival time. Analyses were performed using STATA version 14. The significance level was set at P ≤ 0.05.

Results: A total of 75 patients (17.1%) died due to breast cancer during the study, up to the last follow-up. Numbers of metastatic lymph nodes and histologic grade were significant factors. The cure fraction was estimated to be 58%.

Conclusions: When a cure fraction is not available, the analysis will be changed to standard approaches of survival analysis; however when the data indicate that the cure fraction is available, we suggest analysis of survival data via cure models.
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http://dx.doi.org/10.7314/apjcp.2015.16.16.7359DOI Listing
September 2016

Granzyme h serum levels variations with both reproductive hormone receptors, and related hormone receptors in breast cancer patients.

Iran J Cancer Prev 2014 ;7(1):48-52

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Breast Cancer (BC) is the most common cancer in Iranian women, meanwhile the Iranian patients are relatively young. Granzyme H (GZMH) is a functional cytotoxic serine protease of NK cell granules, which expands the cell death-inducing repertoire of innate immune system. GZMH is constitutively and highly expressed in human NK cells, in order to possess chymotrypsin-like (chymase) enzymatic activity. The purpose of this study was to determine GZMH level, in BC and healthy women.

Methods: 30 breast cancer patients, and 30 control women in premenopausal status, have participated in this study. GZMH, Estrogen levels, and ER, PR have been measured in cancer and healthy women subsequently, as using ELISA, Radioimmunoassay, and Immunohistochemistry methods.

Results: Mean GZMH value was lower in BC than healthy women (p<0.0001).

Conclusion: Our study has implicated existence of suppressor or problem for producing of GZMH in patients group and levels of estrogen couldn't effect on making positive ER, PR.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142953PMC
September 2014

Dosimetric evaluation of Gafchromic EBT2 film for breast intraoperative electron radiotherapy verification.

Phys Med 2015 Feb 16;31(1):37-42. Epub 2014 Sep 16.

Cancer Research Center, Shahid Beheshti University of Medical Science, Shahrdari St 1985717443, Tehran, Iran.

Purpose: Quality assurance (QA) is one of the most important issues that should be addressed for intraoperative electron radiotherapy (IOERT), which is not benefiting from image-based treatment planning system. The aim of this study is to evaluate the dosimetric characteristics of Gafchromic EBT2 film for breast IOERT QA procedure.

Methods: Due to the fact that some dedicated accelerators are being used for IOERT, dependence of the film response to energy, field size, dose rate and incidence angle of electron beam from the LIAC IOERT accelerator was studied. Then, film response curve to breast IOERT doses was obtained and its accuracy was evaluated and justified through comparison to the results of ionometric dosimetry.

Results: The results of this study indicated that there are no significant differences between the film responses at different energies of 6, 8, 10 and 12 MeV (P-value = 0.99). Similarly, no field size dependency was found when evaluating the response of the film to different field sizes ranging from 4 to 10 cm (P-value = 0.94). Film response was found to be independent of the dose rate of intraoperative electron beam (P-value = 0.12). Film response variations with changing the beam incidence angle were not significant (P-value > 0.8). Calibration curve at the dose range of 8-24 Gy had an acceptable accuracy. The difference between the results of film dosimetry and ionometric dosimetry was around 5% which was in agreement with the results of dose uncertainty estimation.

Conclusion: The EBT2 film was found to be a potentially appropriate tool for breast IOERT verification.
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http://dx.doi.org/10.1016/j.ejmp.2014.08.005DOI Listing
February 2015

A survey of breast cancer knowledge and attitude in Iranian women.

J Cancer Res Ther 2012 Jan-Mar;8(1):46-9

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Breast cancer (BC) is the most common cancer among Iranian women. It is recommended that women be under national screening for early detection of cases to improve survival and decrease mortality. Because of shortage of facilities, breast self-examination (BSE) instead of clinical-based examination (CBE) and mammography is advocated as the first step of screening in developing countries including Iran. It is quite clear that the related knowledge, attitude, and practice (KAP) of the community is necessary to have a successful screening program particularly for BSE.

Materials And Methods: A community-based descriptive study on 650 females aged more than 18 years was carried out with a well-structured and valid questionnaire to demonstrate the knowledge and practice of women for BSE, CBE and mammography.

Results: The mean age of participants was 40.72 years with standard deviation (SD) of 9.58. Eighty-two point six percent (82.6%) were married and 48.4% were post graduates. A painless mass (60.8%) and bloody discharge (44.9%) were reported as the two important symptoms for BC. In this assay, 80.3% of participants knew females are at risk of BC and 70.6% of them perceived that early detection and operation in early stages are effective issues. Thirty point eight percent (30.8%) of respondents knew the BSE and this knowledge had significant association with their educational status. Fifty-nine point nine percent (59.9%) of participants were able to do BSE but only 12.9% of respondents practiced BSE regularly.

Conclusion: Community awareness and education level are important elements in BSE as a substitute for traditional screening in BC for early detection.
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http://dx.doi.org/10.4103/0973-1482.95173DOI Listing
August 2012

Effect of the rural rescue system on reducing the mortality rate of landmine victims: a prospective study in Ilam Province, Iran.

Prehosp Disaster Med 2009 Mar-Apr;24(2):126-9

Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Background: In several Iranian provinces, there are large numbers of landmines that threaten the lives of many civilians. Ilam is one of the most polluted areas with 1,086 injuries from landmines between 1989 to 1999, with an overall mortality rate of 36.4%. A remarkable number of deaths occurred before the injured were conveyed to the hospital. In this survey, the effects of on trauma outcome of the use of prehospital trauma life support provided by trained paramedics and rural health workers as first responders were examined.

Methods: In an interventional, prospective study, 4,834 persons (general physicians, nurses, rural health workers, and emergency technicians, high- and low-educated people, layperson villagers, and nomads) were trained in one level of advanced (for general physicians and nurses) and four levels of basic life support courses during two years (2000-2001). Following the training, the data from 288 landmine victims who were referred to the main hospital in Ilam (trauma center) were registered prospectively (2001-2005). The effects of prehospital trauma life support training were assessed by using the Injury Severity Scale (ISS) score and prehospital physiologic severity (PSS) score.

Results: There were 288 injuries from landmines in the Mehran region between 2002 and 2005. The mean ISS score was 20.3 with a median of 13. Forty percent were severely injured with an ISS score >15. Of the injured who received prehospital care at the Mehran Emergency Center, the mean value of the PSS scores was 6.40, which improved to 7.43 in the hospital (p = 0.01; 95% CI for difference -0.72 to -0.45), in comparison with 5.97 in the injured who were conveyed to Ilam Hospital directly (mean of ISS was approximately equal in both groups). The total mortality rate was 27% between 2001 and 2005.

Conclusions: Prehospital educations and training help improve PSS scores and reduce the death toll of landmine accidents in the remote areas.
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http://dx.doi.org/10.1017/s1049023x00006671DOI Listing
August 2009

Treatment management in disaster: a review of the Bam earthquake experience.

Prehosp Disaster Med 2007 Nov-Dec;22(6):517-21

Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

In the early morning of 26 December 2003, Bam, an old city in southeastern Iran, was devastated by an earthquake measuring 6.6 on the Richter scale. Managing such situations always brings about many problems. In the case of the Bam Earthquake, two of the most serious problems were rescue operations and provision of appropriate treatment within a short period of time. By conducting an opinion survey, this study aims to assess different aspects of treatment management, including personnel, the transfer of the injured, equipment, facilities, and treatment planning. Questionnaires containing open questions regarding the management of treatment at five levels were prepared. Those engaged in treatment at different levels, including physicians, treatment workers, military personnel, and executives, were questioned. Several problems were revealed concerning the composition of the treatment forces dispatched, into the region, distribution of the tasks among treatment workers, and the transferring of equipment, and facilities. The most significant problem was a lack of coordination among the organizations responsible for the management of the disaster. A comprehensive disaster plan is required if prompt handling of mass-casualty incidents and coordinating the management of such large-scale disasters are to be ensured.
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http://dx.doi.org/10.1017/s1049023x00005355DOI Listing
September 2008

Survey of Bam earthquake survivors' opinions on medical and health systems services.

Prehosp Disaster Med 2008 May-Jun;23(3):263-8; discussion 269

Trauma Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran.

Introduction: On 26 December 2003, a catastrophic earthquake measuring 6.6 on the Richter scale devastated large areas of the city of Bam in southeastern Iran. More than 40,000 people died, tens of thousands were injured, and almost 20,000 homes were destroyed. Many national and international search-and-rescue teams were dispatched to the area to provide medical and health services and assist in the evacuation of survivors to undamaged areas.

Problem: The purpose of the study was to evaluate the opinions of survivors about medical responses provided, and the process of reconstruction of health infrastructures.

Methods: This was a descriptive study performed two years after the earthquake. Stratified, two-stage area sampling was used to enroll 211 survivors into the survey. A designed questionnaire was applied to evaluate the respondents' opinions about medical and health responses. The respondents were asked to score their satisfaction on a variety of services on a five-point scale, with 1 being "very poor" and 5 being "very good".

Results: Family members and relatives comprised the majority of first responders for those injured or trapped (127, 60.2%). Field hospitals deployed by the Red Crescent, international relief teams, and military forces were the first medical facilities for 98 (46.4%) of the casualties. As denoted by the mean values for the satisfaction scores, transportation by aircraft to the backup hospitals received the highest score (4.2), followed by international assistance (4.1), first medical care (3.5), search and rescue (3.3), primary transportation (3.1), and reconstruction and the quality of access to the infrastructures of the city (2.6). Two years after the earthquake, 151 (71.5%) respondents still were living in connexes (temporary accommodations or shelters for victims to live in; resemble a small hotel), only 33 (15.6%) had access to safe drinking water, and 44 (20.9%) did not have sufficient supplies of sanitary food.

Conclusions: In addition to reinforcing the medical and health infrastructures of a society in accordance with geographical and architectural characteristics, effective air evacuation and relief missions carried out by experienced international relief teams can play an important role in the appropriate management of approximately 30,000 casualties after a catastrophic event, such as experience with the Bam Earthquake.
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October 2008