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Jul-Sep 2019
Volume 15 | Issue 5
Page Nos. 953-1200

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REVIEW ARTICLES  

Frondoside A is a potential anticancer agent from sea cucumbers p. 953
Fatma Hussain Sajwani
DOI:10.4103/jcrt.JCRT_1427_16  PMID:31603094
Cancer is a leading cause of death worldwide. Although high cure rates are achievable with current available drugs, this is not without side effects. Hence, attention has been shifted to alternative anticancer agents coming from natural products as treatment options. Extracts from marine sea cucumbers have been investigated for such properties. Frondoside A is a natural glycoside extracted from the sea cucumber, Cucumaria frondosa, which has been used as a traditional remedy, recently, the extract was found to have potential anti-tumor properties. This narrative review aimed at critically analyzing and summarizing the literature available regarding Frondoside A anticancer properties. For that, scientific databases such as PubMed, EMBASE, and ScienceDirect were searched for the keywords; Frondoside A, cancer, metastasis, anticancer properties, and sea cucumbers. Articles in languages other than English were excluded from the study. Such review will help researchers to better tailor future experiments and will enrich the knowledge about natural compounds consumed as traditional substances.
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Epigenetic therapies in patients with solid tumors: Focus on monotherapy with deoxyribonucleic acid methyltransferase inhibitors and histone deacetylase inhibitors p. 961
Rygiel Katarzyna, Bulas Lucyna
DOI:10.4103/jcrt.JCRT_403_17  PMID:31603095
Epigenomics is the study of the gene expression changes due to epigenetic processes and not due to the deoxyribonucleic acid (DNA) base sequence alterations. The key mechanisms of epigenetic regulation include DNA methylation, histone modifications, and noncoding RNAs. Epigenetic alterations in cancer are predominantly linked with hypermethylation of promoters of the tumor suppressor genes, global DNA hypomethylation, and increased expression of histone deacetylases (HDAC). There is a growing need to investigate epigenetic patterns and to provide safe and effective, innovative therapeutic strategies for oncology patients, who did not improve on traditional anticancer regimens. The epi-drugs (e.g., DNA methyltransferase inhibitors, e.g., azacitidine and decitabine and HDAC inhibitors, e.g., vorinostat and romidepsin) have been approved for the clinical use. In this paper, we provide a brief overview of the mechanisms of action and targets for novel epi-drugs, focusing on their potential clinical applications in patients with solid tumors, resistant to standard oncology treatments.
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ORIGINAL ARTICLES Top

Bone metastases incidence and its correlation with hormonal and human epidermal growth factor receptor 2 neu receptors in breast cancer p. 971
Ananya Pareek, OP Singh, Veenita Yogi, HU Ghori, Vivek Tiwari, Pallavi Redhu
DOI:10.4103/jcrt.JCRT_235_18  PMID:31603096
Aim: In this paper, we present a prospective observational study, which determines the incidence of bone metastases and its correlation with hormonal receptors (estrogen receptor [ER]/progesterone receptor [PR]) and human epidermal growth factor receptor 2 (HER2) in breast cancer. Materials and Methods: From October of 2015 to July 2017, 262 patients were eligible for the study, of which 98 patients presented/developed bone metastases. ER/PR and HER2 receptor status were determined, and bone scintigraphy with a technetium-99 m was carried out on each patient during the study. Results: The incidence rate of bone metastases as found in this study was 25.25%, and the mean and median age at diagnosis were 47.23 and 46, respectively (age range = 28–80). Bone metastases were more prevalent in ER-positive tumors (P = 0.043), tumors with lymph node positivity (P = 0.002), and lower grade tumors (P = 0.002), whereas visceral metastases were more common with ER-tumors (P = 0.005), tumors with higher grade (P = 0.012), and tumors with lymph node positivity (P = 0.034). In this study cohort, the spine and pelvis were the most commonly involved subsites of bone metastases (P < 0.001). Conclusion: This study demonstrates that the metastatic patterns in breast cancer strongly correlate with various breast cancer subtypes, mainly designated by ER, PR, and HER2. Hormone receptor-positive tumors show a predilection for bones as the first site of relapse compared to hormone-receptor-negative tumors which have a proclivity to develop as visceral metastases.
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Infertility as a risk factor for breast cancer: Results from a hospital-based case–control study p. 976
Maryam Ghanbari Andarieh, Mouloud Agajani Delavar, Dariush Moslemi, Mahmoud Haji Ahmadi, Ebrahim Zabihi, Sedighe Esmaeilzadeh
DOI:10.4103/jcrt.JCRT_905_16  PMID:31603097
Context: Breast cancer is the most common cancer in women worldwide and its prevalence is increasing. Aims: The aim of this study was to investigate the extent to which a history of infertility can present as risk factors for breast cancer. Settings and Design: This was a hospital-based case–control study. Subjects and Methods: In this study, 1177 women with breast cancer were participated for assessing the risk for this cancer. The control was 1204 women with self-reported free-cancer history who were matched in terms of age and residence. Statistical Analysis Used: Using logistic regression, it was examined whether infertility is a risk factor of case–control status in addition to marriage age, menarche age, body mass index, number of pregnancies, family history of breast cancer, and previous oral contraceptive use. The data were considered significant at P ≤ 0.05. Results: Infertility history was reported in 12.5% (n = 147) of the cases and 5.8% (n = 70) of the controls. Infertility history was a relevant risk for case–control study in addition to other risk factors (odds ratio: 2.43; 95% confidence interval, 3.34–1.77). Conclusions: This study found that infertility may be as the main risk factor for breast cancer in Iranian women, therefore, doing breast screening in women who have one or more risk factors, must receive more emphasis.
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Assessment of human epidermal growth factor receptor 2/neu gene amplification and expression as a biomarker for radiotherapy and hormonal-treated breast cancer patients in upper Egypt p. 981
Marwa Khairy Essmat, Mostafa A Abdelwanis, Eman Zaky Mosad, Tarek K El-Maghraby, Ahmed Egiza Othman
DOI:10.4103/jcrt.JCRT_42_17  PMID:31603098
Background: Breast cancer plays major public health in Egyptian women. In upper Egypt, There is an increase in the incidence of breast cancer compared to other Egyptian areas without know the reasons. In this study, we aimed to evaluate the potential of HER-2/neu status as one of the important markers to classify the women suffering from breast cancer in upper Egypt and monitoring the responsiveness to different therapies. Settings and Design: The present study was performed on 67 female breast cancer patients in the South Egypt Cancer Institute to evaluate HER-2/neu gene amplification and expression. Patients and Methods: Tissue samples were used for immunohistological analysis of endocrine receptors, HER-2/neu, and HER-2/neu gene amplification. In addition, the blood samples were also used to determine HER-2/neu gene expression. Statistical Analysis: All statistical analyses were performed using Chi-square test. The statistical difference is considered statistically significant at P < 0.05. Results: There was a statistically significant association between HER-2/neu gene expression and the age of patients. There is decrease in the level of HER-2/neu mRNA expression in group treated with chemotherapy and group treated with chemotherapy and radiotherapy compared to each group baseline level of HER-2/neu mRNA expression before treatment. On the contrary, the group treated with chemotherapy, radiotherapy, and hormonal therapy revealed increase on the level of HER-2/neu mRNA expression when compared with their baseline for the same patients before treatment. Conclusion: We need further studies on the large group of upper Egypt breast cancer patients to confirm that the level of HER-2/neu mRNA expression can be used as a marker for classified them and their response to different treatment.
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Expression of androgen receptor in primary breast carcinoma and its relation with clinicopathologic features, estrogen, progesterone, and her-2 receptor status p. 989
Gnanapriya Vellaisamy, Rajalakshmi Tirumalae, YK Inchara
DOI:10.4103/jcrt.JCRT_572_17  PMID:31603099
Introduction: The role of estrogen/progesterone receptors (ER/PR) is well-established with respect to therapy and prognosis of breast carcinoma. However, the role of androgen receptor (AR) expression is unclear in the Indian context. The objective is to study the following: (a) Expression of AR in resection specimens of ductal carcinomas, (b) Relationship of AR with clinicopathologic features, ER, PR, and Her-2 status. Materials and Methods: This study included female patients with infiltrating ductal carcinoma with a minimum of 10 axillary lymph nodes, whose hormone receptor status data were available. Demographic and histopathologic details were retrieved. Immunohistochemistry for AR was done and considered positive if ≥10% of tumor cells showed nuclear staining and compared to various clinicopathologic features. Results: A total of 71 cases were included in the study. AR expression was noted in 52% of cases. Of the 35 ER and/or PR expressing tumors, AR was positive in 24 cases. In contrast, of the 36 ER/PR-negative tumors, AR was expressed in only 13 cases (P = 0.006). There was no significant difference in the expression of AR between Her-2 positive and negative cases. AR positivity was noted in 23% of triple-negative tumors. Age did not show an influence on AR status. Among histopathologic parameters, low-grade tumors were significantly associated with AR expression (P = 0.018) while tumor size, lymphovascular emboli, and nodal status were not. Within the follow-up period, four patients from AR-positive group developed distant metastasis. Conclusion: Indian patients with breast carcinoma have a higher AR expression in low-grade and ER/PR-positive tumors, in concordance with Western studies. A good number of triple-negative tumors also express AR, which needs further evaluation.
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Intraoperative radiotherapy with electrons as partial breast irradiation in limited stage breast cancer: Early term clinical and cosmetic outcomes p. 994
Gülhan Güler Avci, Yildiz Güney, Bülent Küçükpilakci, Tamer Çalikoğlu, Mehmet Ali Gülçelik, Cihangir Özaslan
DOI:10.4103/jcrt.JCRT_191_17  PMID:31603100
Purpose: We aimed to report the experience of intraoperative electron radiation therapy (IOERT) with Mobetron (Intraop Medical Incorporated, Santa Clara, CA, USA) as a partial breast irradiation (PBI) for patients with early-stage breast cancer and explanation of IOERT application and present early clinical and cosmetic result. Materials and Methods: Between November 2012 and February 2014, in Ankara Oncology Hospital, Radiation Oncology Clinic, was performed IOERT as a PBI with a single dose of 21 Gy for 21selected patients. Median tumor size was 1.5 cm (range, 0.6–2.8 cm). Median treatment duration was 2.04 min (range, 1.26–2.44 min). According to final pathology, two patients were found to have close margin and mastectomy was applied. Three cases (two were N1 mic and one case had perineural invasion and tumor size was >2 cm) received whole breast irradiation. Results: Median follow-up time was 3 years (range, 26–42 months). One patient died because of nonbreast cancer reason, all of the other patients (except one) alive without disease. There was no Grade 3 or 4 toxicities related to the IOERT. Good or excellent cosmesis was revealed 79% (15/19) and 95% (18/19), by physician and patient, respectively. Conclusion: IOERT, for patients with early-stage breast cancer as a part of breast-conserving treatment, offer patients better cosmetic results with less skin toxicity and increases comfort of patients by shortening duration of treatment time.
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Conformal electron beam radiotherapy using custom-made step bolus for postmastectomy chest wall irradiation: An institutional experience p. 999
Balasubramanian Ananthi, Kunjithapatham Bhuvana, Rangad Viswanathan Faith, Ganesarajah Selvaluxmy, Nagarajan Vivekanandan, Iyer Priya
DOI:10.4103/jcrt.JCRT_69_17  PMID:31603101
Background: Postmastectomy radiation (PMRT) to the chest wall using electron beam treatment with uniform bolus was practiced at our institution. The planning target volume (PTV) included the chest wall and the internal mammary nodes (IMN) along with supraclavicular nodal regions. The varying thickness of the postmastectomy chest wall and the varying position of the IMN resulted in dose inhomogeneity in the PTV. In addition, there was the risk of increased lung and cardiac doses. In this prospective study, we report the making of a custom-made bolus using dental wax called “step bolus.” Materials and Methods: From March 2010 to January 2011, 167 patients received PMRT. As conformal photon plans were not acceptable in 48 patients, they were treated with single energy electrons and custom-made bolus. Results: Addition of the step bolus improved dose distribution to the PTV reduced the mean lung dose %, the mean heart dose % and lung dose (D10, D20, D30, D50, and D70). Forty-seven patients had Grade 2, and one patient had Grade 3 skin toxicity. Acute symptomatic radiation pneumonitis was observed in one patient. At 5 years, 29 patients were alive with a median follow-up of 32 months and no local recurrences were observed. One patient died of myocardial infarction unrelated to treatment, one patient did not come for follow-up, 22 patients had systemic metastases, and 24 patients were disease free. Conclusion: A custom-made step bolus using dental wax can be used for tissue compensation in electron beam therapy with resulting good local disease control and acceptable toxicity.
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Dual partial arc volumetric-modulated arc therapy: The game changer for accelerated hypofractionated whole-breast radiotherapy with simultaneous integrated tumor cavity boost in early breast cancer - A comparative dosimetric study with single partial arc volumetric-modulated arc therapy p. 1005
Dodul Mondal, Pramod Kumar Julka, Daya Nand Sharma, Macharla Anjaneyelu Laviraj, Manisha Jana, Vineet Kumar Kamal, Suryanarayan V S Deo, Randeep Guleria, Goura K Rath
DOI:10.4103/jcrt.JCRT_922_17  PMID:31603102
Introduction: In a previous study, we demonstrated clinical and dosimetric feasibility of single partial arc volumetric modulated arc therapy (VMAT) for accelerated hypofractionated whole breast radiotherapy with simultaneous integrated boost (SIB) to lumpectomy cavity for early breast cancer. In this dosimetric study, we compared dual partial arcs versus single arc. Patients and Methods: Fifteen consecutive patients for treatment with hypofractionated accelerated radiotherapy with SIB using VMAT were planned with single partial arc in an earlier study, initial result of which is published elsewhere. The comparative dosimetric plan was created using two partial arcs. Skewness and kurtosis test, Paired Student's t-test, and Wilcoxon signed-rank test were applied for statistical analysis. P < 0.05 was considered statistically significant. Results: Most planning targets are better achieved with dual arc technique. Coverage of planning target volume (PTV) whole breast (PTVWB) and PTV lumpectomy cavity (PTVBOOST) was significantly improved with dual partial arc without significant difference in conformity index and homogeneity index. Dual arc improved dosimetric parameter significantly. Mean dose (Dmean) and maximum dose (Dmax) of whole breast PTV as well as Dmax of PTVBOOST; ipsilateral and contralateral lung Dmean, Dmax, 5 Gy volume (V5); contralateral lung Dmean, Dmax, V5; Heart V25 and V18; Dmean of 5 mm thickness skin; Dmean and Dmax of ribs; and Dmean and Dmax of contralateral breast were improved with dual arc. Conclusion: This is first of its kind study establishing the advantage of dual partial arcs in the current context. Dual partial arcs improved dosimetry over single partial arc. Significant dose reduction can be achieved for multiple crucial organs at risk.
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Two-dimensional dose reconstruction using scatter correction of portal images p. 1011
Akbar Anvari, Parham Alaei, Mohammad Mohammadi
DOI:10.4103/jcrt.JCRT_376_17  PMID:31603103
Context: Electronic portal imaging devices (EPIDs) could potentially be useful for patient setup verification and are also increasingly used for dosimetric verification. The accuracy of EPID for dose verification is dependent on the dose-response characteristics, and without a comprehensive evaluation of dose-response characteristics, EPIDs should not be used clinically. Aims: A scatter correction method is presented which is based on experimental data of a two-dimensional (2D) ion chamber array. An accurate algorithm for 2D dose reconstruction at midplane using portal images for in vivo dose verification has been developed. Subjects and Methods: The procedure of scatter correction and dose reconstruction was based on the application of several corrections for beam attenuation, and off-axis factors, measured using a 2D ion chamber array. 2D dose was reconstructed in slab phantom, OCTAVIUS 4D system, and patient, by back projection of transit dose map at EPID-sensitive layer using percentage depth dose data and inverse square. Verification of the developed algorithm was performed by comparing dose values reconstructed in OCTAVIUS 4D system and with that provided by a treatment planning system. Results: The gamma analysis for dose planes within the OCTAVIUS 4D system showed 98% ±1% passing rate, using a 3%/3 mm pass criteria. Applying the algorithm for dose reconstruction in patient pelvic plans showed gamma passing rate of 96% ±2% using the same pass criteria. Conclusions: An accurate empirical algorithm for 2D patient dose reconstruction has been developed. The algorithm was applied to phantom and patient data sets and is able to calculate dose in the midplane. Results indicate that the EPID dose reconstruction algorithm presented in this work is suitable for clinical implementation.
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Measurement of the contralateral breast photon and neutron dose in breast cancer radiotherapy: A Monte Carlo study p. 1018
Hamed Bagheri, Bagher Farhood, Seied Rabi Mahdavi, Babak Shekarchi, Farhad Manouchehri, Malahat Esfandbod
DOI:10.4103/jcrt.JCRT_1426_16  PMID:31603104
Introduction: This study aimed to calculate the photon and neutron doses received to the contralateral breast (CB) during breast cancer radiotherapy for various field sizes in the presence of a physical wedge. Materials and Methods: Varian 2100 C/D linear accelerator was simulated using a MCNP4C Monte Carlo code. Then, a phantom of real female chest was simulated and the treatment planning was carried out on tumoral breast (left breast). Finally, the received photon and neutron doses to CB (right breast) were calculated in the presence of a physical wedge for 18 MV photon beam energy. These calculations were performed for different field sizes including 11 cm × 13 cm, 11 cm × 17 cm, and 11 cm × 21 cm. Results: The findings showed that the received doses (both of the photon and neutron) to CB in the presence of a physical wedge for 11 cm × 13 cm, 11 cm × 17 cm, and 11 cm × 21 cm field sizes were 9.87%, 12.91%, and 27.37% of the prescribed dose, respectively. In addition, the results showed that the received photon and neutron doses to CB increased with increment in the field size. Conclusion: From the results of this study, it is concluded that the received photon and neutron doses to CB in the presence of a physical wedge is relatively more, and therefore, they should be reduced to as low as possible. Therefore, using a dynamic wedge instead of a physical wedge or field-in-field technique is suggested.
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Impact of focality on prognostication of early and operable breast carcinomas of no special type p. 1024
Preithy Uthamalingam, Bharath Rangarajan, Preethi Sekar, Sangita Mehta
DOI:10.4103/jcrt.JCRT_804_17  PMID:31603105
Background and Objectives: Multifocal/multicentric (MF/MC) breast carcinomas are not uncommon and its prognostic significance debated. We attempted to analyze the association of focality and prognostic factors in operated pT1 and pT2 breast carcinomas of no special type (NST). Materials and Methods: Retrospectively identified pathologically proven 124 unifocal (UF) and 49 MF/MC pT1 and pT2 breast carcinomas of NST over the past three years were compared in terms of clinical and pathological factors. Results: The patients with MF/MC NST tumors were more likely to undergo radical surgery (P = 0.028). The tumors showed higher incidence of lymphovascular invasion (P = 0.024), perineural invasion (P = 0.046), ductal carcinoma in situ component (P < 0.001), higher number of positive axillary lymph nodes (P < 0.001), and higher anatomical staging (P = 0.048) when compared to the UF counterparts. Morphological intertumoral heterogeneity was noted in MF/MC tumors in 16 of 49 cases (32.65%). Conclusion: Most published studies on MF breast cancers have included all histological types and varying definitions. We included only pathologically defined stages and a single histological type to ensure “purity” of the groups. Higher anatomic staging and morphological interlesional heterogeneity suggest that early MF/MC tumors represent multiple primaries with a different biology. Careful consideration of features of each focus needs to be considered when deciding appropriate adjuvant therapy and for accurately prognosticating these patients. Immunohistochemical and morphological (grade) heterogeneity between the different foci may pose problems with “prognostic stage grouping” these tumors according to the American Joint Committee on Cancer staging system (8th edition).
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Does addition of postmastectomy radiotherapy improve outcome of patients with pT1-2, N0 triple negative breast cancer as compared to breast conservation therapy? p. 1031
Rajeev Kavalakara Raghavan, Shabna Ibrahim, KM Jagathnath Krishna, Beela Sarah Mathew
DOI:10.4103/jcrt.JCRT_974_17  PMID:31603106
Background: Triple-negative breast cancers (TNBCs) form a heterogeneous group of cancers typically exhibiting an aggressive behavior resulting in increased risk of locoregional relapse (LRR) and distant metastases. The effect of radiotherapy on LRR risk and overall survival (OS) in women treated with mastectomy alone for early-stage TNBC remains unclear. Aim: The aim of this study is to compare the locoregional recurrence rate, disease-free survival (DFS), and OS following breast conservation therapy (BCT) or modified radical mastectomy (MRM) alone in women with stage I and IIA TNBC and to assess the impact of tumor and treatment-related factors. Materials and Methods: Patients with early-stage (pT1-2, N0) TNBC-treated between January 1, 2010, and December 31, 2011, were identified from the hospital-based registry records. The mean age was 48 years. Forty-nine patients underwent BCT, and 121 underwent MRM. The majority of the patients in both groups had T2 and grade 3 disease. None of the patients had margin positive status after surgery. Five patients had lymphovascular invasion (LVI). Results: At a median follow-up of 50 months (range: 4–83 months), there was no locoregional recurrence (LRR) in either arm. Eight patients relapsed, six developed distant metastases, and one patient each had a new primary in the contralateral breast and ovary. Two patients died of disseminated cancer, one each in the BCT and MRM groups. The five-year DFS was 95.8% and 91.1% for the BCT group and MRM group, respectively, (P = 0.83). The corresponding 5-year OS was 98% and 97.5% (P = 0.527). There was no statistically significant difference in outcome based on age, grade, LVI, or margin status between both groups. Conclusion: This retrospective analysis identified no statistically significant difference in outcome regarding LRR, DFS, or OS in patients treated without adjuvant radiation for women with pT1-T2N0 TNBC who underwent MRM in comparison to BCT.
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A comparative study for surface dose evaluation in conventional treatment of carcinoma breast patients irradiated with Co-60 and 6 MV radiation beam p. 1035
Ranjit Singh, Arun Singh Oinam, Gaurav Trivedi, Harpreet Singh Kainth, Jangvir Singh Shahi, Baljinder Singh, Rakesh Kapoor
DOI:10.4103/jcrt.JCRT_789_17  PMID:31603107
Aim: In the present study, surface doses within the target area and contralateral breast (CLB) received during conventional treatment of carcinoma breast are evaluate and compared for treatment on two different beam energies, i.e., Co-60 γ-ray and 6 MV X-ray beams with thermoluminescent dosimeter, LiF:Mg, Ti (TLD-100). Materials and Methods: The study includes a group of 23 patients comprising 11 patients treated with Co-60 γ-ray beam and 12 patients by 6 MV X-ray beam. Results and Discussion: The treatment using Co-60 γ-ray and 6 MV X-ray beams contributes an average percentage dose of 8.15% ± 0.56% and 4.73% ± 0.94%, respectively, to CLB in mastectomy patients. The contribution of tangential fields (mastectomy) to the CLB doses ranges between 12.71 and 16.40 cGy (5.45%–7.03%) for treatment with Co-60 γ-ray beam and 6.33–10.95 cGy (1.86–4.69%) for treatment with 6 MV X-ray beam. The supraclavicular field (SCF) contributes 1.45%–1.93% and 1.02%–1.43% for treatment with Co-60 γ-ray and 6 MV X-ray beams, respectively. The average surface dose (normalized with breast dose) 89.1% ± 8.5% for Co-60 beam in the SCF region differs significantly from the 60.2% ± 13.0% value for 6 MV X-ray beam. Conclusion: The CLB doses for mastectomy patients are higher for Co-60 beam as compared to 6 MV X-ray beam, and better dose homogeneity is achieved within the irradiated breast from 6 MV X-ray beam. The CLB doses are slightly higher for patients treated with breast conservative radiotherapy or lumpectomy. The average surface dose to SCF decreases by ~30% of treated breast dose for treatment with 6 MV X-ray beam.
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Clinical implementation of brass mesh bolus for chest wall postmastectomy radiotherapy and film dosimetry for surface dose estimates p. 1042
Dilson Lobo, Sourjya Banerjee, PU Saxena, Ramamoorthy Ravichandran, Challapalli Srinivas, Suman Kumar Putha, Dinesh Pai Kasturi
DOI:10.4103/jcrt.JCRT_1034_17  PMID:31603108
Objective: This study presents the dosimetric data taken with radiochromic EBT3 film with brass mesh bolus using solid water and semi-breast phantoms, and its clinical implementation to analyze the surface dose estimates to the chest wall in postmastectomy radiotherapy (PMRT) patients. Materials and Methods: Water-equivalent thickness of brass bolus was estimated with solid water phantom under 6 megavoltage photon beam. Following measurements with film were taken with no bolus, 1, 2, and 3 layers of brass bolus: (a) surface doses on solid water phantom with normal incidence and on curved surface of a locally fabricated cylindrical semi-breast phantom for tangential field irradiation, (b) depth doses (in solid phantom), and (c) surface dose measurements around the scar area in six patients undergoing PMRT with prescribed dose of 50 Gy in 25 fractions. Results: Water-equivalent thickness (per layer) of brass bolus 2.09 ± 0.13 mm was calculated. Surface dose measured by film under the bolus with solid water phantom increased from 25.2% ±0.9% without bolus to 62.5% ± 3.1%, 80.1% ± 1.5%, and 104.4% ± 1.7% with 1, 2, and 3 layers of bolus, respectively. Corresponding observations with semi-breast phantom were 32.6% ± 5.3% without bolus to 96.7% ± 9.1%, 107.3% ± 9.0%, and 110.2% ± 8.7%, respectively. A film measurement shows that the dose at depths of 3, 5, and 10 cm is nearly same with or without brass bolus and the percentage difference is <1.5% at these depths. Mean surface doses from 6 patients treated with brass bolus ranged from 79.5% to 84.9%. The bolus application was discontinued between 18th and 23rd fractions on the development of Grade 2 skin toxicity for different patients. The total skin dose to chest wall for a patient was 3699 cGy from overall treatment with and without bolus. Conclusions: Brass mesh bolus does not significantly change dose at depths, and the surface dose is increased. This may be used as a substitute for tissue-equivalent bolus to improve surface conformity in PMRT.
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Favorable results of patients with pT1a, b, c, lymph node-negative early breast cancer in the long interval p. 1051
Nilufer Bulut, Arife Ulas, Kadri Altundag
DOI:10.4103/jcrt.JCRT_1275_16  PMID:31603109
Background: The clinical characteristics of patients who had lymph node-negative early breast cancer were assessed. Patients and Methods: We assessed a total of 576 patients in the study, including 74 patients (12.8%) with T1a, 119 patients (20.7%) T1b, and 367 patients (63.7%) with T1c. Patients with T1 tumors were further classified into three groups according to hormone receptor (HR) and human epidermal growth factor-receptor 2 (HER2) status. Results: In patients with T1a, the disease-free survival (DFS) rate was 98.4% at 2 years (P = 0.001). In subgroup analysis of early breast cancers, 10-year-DFS rates of the patients in HR+/HER2–, HR–/HER2+, and HR–/HER2– subgroups were not significantly different (P = 0.917). Conclusion: The T1a group had a worse prognosis than T1b and T1c groups in second years (P = 0.001); however, there was not statistically important difference between HR+, HER2+ and triple negative subgroups (P = 0.917). Although there are differences in patients and tumor features, the prognosis of patients with T1a, b, c N0M0 breast cancer is excellent.
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Squamous cell carcinoma of the breast: A retrospective study p. 1057
Maher Soliman
DOI:10.4103/jcrt.JCRT_303_17  PMID:31603110
Background: Squamous cell carcinoma (SCC) of the breast is an extremely rare tumor with vague natural behavior and treatment. The purpose of this study was to identify the clinicopathological features and treatment results of this rare type of breast cancer. Materials and Methods: The medical files of patients with SCC of the breast presented to Alexandria Main University Hospital during the period from January 1990 to January 2010 were retrospectively reviewed, regarding clinicopathological characteristics and treatment outcome and analyzed. Results: A total of 17 patients were included in this analysis. The median age was 50 years. All patients presented with breast mass. The majority of tumors (88.2%) was negative for hormone receptors. Two-thirds of patients had early T-stage. All patients underwent surgery in our center. Adjuvant tamoxifen was given for two patients. Twelve patients (70.6%) received different adjuvant chemotherapy protocols, and eight patients received radiotherapy. The median disease-free survival was 24 months, and the median overall survival was 40 months. Patients received adjuvant chemotherapy had a statistically significant better disease-free survival (P = 0.014) and overall survival (P = 0.019) compared to patients treated without chemotherapy. Radiotherapy had no significant impact on either disease-free survival or overall survival. Conclusions: SCC of the breast is a very aggressive tumor, and adjuvant chemotherapy should be strongly considered.
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Thiol-disulfide homeostasis in breast cancer patients p. 1062
Mehmet Ali Eryilmaz, Betül Kozanhan, Ibrahim Solak, Çigdem Damla Çetinkaya, Salim Neselioglu, Özcan Erel
DOI:10.4103/jcrt.JCRT_553_17  PMID:31603111
Objective: The aim of our study is to assess thiol-disulfide homeostasis (TDH), which is a biomarker of systemic oxidative stress, in breast cancer patients. Materials and Methods: Thirty-seven breast cancer patients and 31 age-matched healthy volunteers were enrolled in this study. Serum native thiol, disulfide, and total thiol levels and disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were analyzed using a novel colorimetric method. Results: Serum native thiol level was statistically significantly lower in breast cancer patients (350.39 ± 7.15) than in healthy controls (380.60 ± 7.35) (P = 0.008). Serum disulfide level was statistically significantly higher in breast cancer patients (24.96 ± 0.85) than in healthy controls (19.25 ± 1.34) (P = 0.002). Conclusion: To our knowledge, this study is the first study in the literature that investigated TDH in breast cancer patients. We have concluded that an alteration in TDH due to oxidative stress is likely to have a role in the pathogenesis of breast cancer.
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Expression of major histocompatibility complex class I polypeptide-related sequence B in adipose-derived stem cells from breast cancer patients and normal individuals p. 1067
Zahra Mansourabadi, Mahboobeh Razmkhah, Maryam Sadat Mohtasebi, Abdol-Rasoul Talei, Abbas Ghaderi
DOI:10.4103/jcrt.JCRT_866_16  PMID:31603112
Context: Through the expression of different immunomodulatory molecules, mesenchymal stem cells (MSCs) play a significant role in the regulation of immune responses against tumor cells. Herein, the expression of major histocompatibility complex class I polypeptide-related sequence B (MIC B) as an immunomodulatory molecule was investigated on adipose-derived stem cells (ASCs) isolated from breast cancer patients (Stage II and III) and healthy individuals. Materials and Methods: ASCs were isolated enzymatically, and the expression of MIC B was measured using quantitative real-time polymerase chain reaction method before and after treatment with interferon γ (IFN-γ). The concentration of MIC B in the supernatant of ASCs and also sera of breast cancer and normal individuals were determined using ELISA method. Results: The expression of MIC B in normal ASCs and Stage II ASCs was higher than Stage III ASCs. However, after treatment with IFN-γ expression of MIC B in ASCs was conversely changed as cancer ASCs showed approximately 3.5 fold higher expression of MIC B compared to normal ASCs. The mRNA expression of MIC B in Stage III, Stage II, and normal ASCs showed 61 (P = 0.02), 13 (P = 0.01) and 3 (P > 0.05) fold higher expression after stimulation with IFN-γ compared to cells with no stimulation. Conclusion: Expression of MIC B and upregulation of this molecule in response to IFN-γ in cancer ASCs draw attention to the effective role of MSCs in the tumor microenvironment. However, more studies will be needed to further elucidate Natural-killer Group 2, member D (NKG2D) ligands-dependent immunomodulatory roles of ASCs in the tumor progression.
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The synergistic cytotoxic effects of doxorubicin and Viola odorata extract on human breast cancer cell line T47-D p. 1073
Shirin Zeinoddini, Mohammad Nabiuni, Hanieh Jalali
DOI:10.4103/jcrt.JCRT_990_17  PMID:31603113
Background: Breast cancer accounts for one-third of cancer cases in women. Doxorubicin (Dox) is one of the chemotherapeutical compounds widely used to treat breast cancer. Chemical drugs have several side effects and their continuous administration leads to drug resistance in patients. To decrease such side effects in cancer treatment, combination therapy as well as application of natural and herbal compounds has been taken into consideration. The aim of this study was to investigate the cytotoxic effect of Viola odorata (Vo) extract on T47-D human breast cancer cells, alone and in combination with Dox. Materials and Methods: The cytotoxic effects of V. odorata and Dox were studied by morphological examination and 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flowcytometric analysis was performed to determine the type of cell death. Moreover, scratch healing assay was conducted to investigate antimigration effect of V. odorata. Results: The results of MTT assay showed that V. odorata and Dox-induced cell death in T47-D cells in a dose- and time-dependent manner. Morphological analysis revealed that V. odorata and Dox-induced features of apoptotic cell death in T47-D cells. These results were confirmed by flow cytometry analysis. Scratch healing assay revealed that migration rate was reduced in the V. odorata- treated cells. Conclusions: Our findings suggest that components of V. odorata exert antitumor effects on human breast cancer and could be administered with lower doses of antitumor agent Dox, in combination therapy, to decrease its side effects.
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Cytotoxic and genotoxic effects of an endemic plant of Turkey Salvia kronenburgii on breast cancer cell lines p. 1080
Aysegul Çebi, Egemen Akgün, Serap Çelikler, Mehmet Firat, Mustafa Zafer Özel, Engin Ulukaya, Ferda Ari
DOI:10.4103/jcrt.JCRT_1322_16  PMID:31603114
Context: The natural products derived from plants are the important sources that can be used for breast cancer treatment. Salvia species and their derived products were recommended as potential antitumor substances. Aim: The potential cytotoxic and genotoxic effects of Salvia kronenburgii have been investigated on breast cancer cell lines, MCF-7 and MDA-MB-231. Materials and Methods: Determination of chemical compounds of S. kronenburgii was done using a gas chromatography coupled to time-of-flight mass spectrometry system and a dual-stage commercial thermal desorption injector. Growth inhibition of the S. kronenburgii was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and ATP viability assays. The cell death mode was detected by fluorescent dyes. Genotoxic effect of S. kronenburgii was measured by comet assay. Results: S. kronenburgii showed antiproliferative effect in a dose-dependent manner on MCF-7 and MDA-MB-231 cell lines by inducing apoptosis-like cell death. The pyknotic cell nuclei were observed at the cell lines in response to S. kronenburgii. Furthermore, significant increase was shown in genetic damage index and frequencies in the damaged cells. Conclusion: S. kronenburgii might be a promising natural source for cancer therapy. Further experiments need to be done in vivo to understand of the anticancer effects of this plant.
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Epidemiological characteristics of breast cancer patients attending a tertiary health-care institute in the National Capital Territory of India p. 1087
Nighat Yaseen Sofi, Monika Jain, Umesh Kapil, Chander Prakash Yadav
DOI:10.4103/jcrt.JCRT_868_16  PMID:31603115
Background: Limited data are available on the epidemiology of breast cancer (BC) in India. Objective: To study the epidemiological characteristics of BC patients attending a tertiary care hospital in National Capital Territory of India. Materials and Methods: A cross-sectional study was conducted and information from 320 women with confirmed BC was collected on a questionnaire for demographic profile, socioeconomic status (SES), reproductive risk factors, and family history of BC. Information on clinical presentation and staging of BC was recorded. Anthropometric assessment for body mass index (BMI) was done. Data were analyzed and presented as mean ± standard deviation and frequency tables. Results: The mean age at diagnosis of BC was 47 ± 10 years. Fifty-three percent of patients were illiterate or only primary school education. About 74% of patients were from urban areas. Only 11% of patients were from upper SES and 26% from lower SES. Forty-seven percent of patients had stage II followed by 36% with stage III BC. About 15% patients had experienced early menarche (<13 years of age) and 15% of women had attained late menopause (>51 years of age). About 42% of patients had <3 children and 15% patients had a family history of BC. About 38% patients were overweight and 21% were obese. Conclusion: Other than the established risk factors, other factors such as lack of education, SES, and higher BMI were present in our study. A higher percentage of women were diagnosed with BC at later stages. There is a need for educating women about BC, self-examination of breast, and screening programs for early detection of BC.
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Circulating miR-21 and miR-155 as potential noninvasive biomarkers in Iranian Azeri patients with breast carcinoma p. 1092
Elaheh Soleimanpour, Esmaeil Babaei, Mohammad-Ali Hosseinpour-Feizi, Vahid Montazeri
DOI:10.4103/jcrt.JCRT_1227_16  PMID:31603116
Background: Breast cancer (BC) is the most common cause of cancer-related mortality among women. Despite recent advances in diagnosis and prognosis of breast carcinomas, noninvasive biomarkers have been poorly identified. We evaluated the biomarker potential of miR-21 and miR-155 in tissue and plasma specimens of Iranian Azeri patients. Materials and Methods: Tumor specimens, paired nontumoral adjacent tissues, and matched plasma samples were collected from a number of thirty Iranian Azeri women with breast carcinoma. Plasma of healthy women was used as the control. The relative expression of miR-21 and miR-155 was measured by real-time polymerase chain reaction. Results: Our data revealed that the expression levels of miR-21 and miR-155 in tumor tissues are significantly higher than paired nontumoral adjacent specimens (P < 0.05). Furthermore, receiver operating characteristic (ROC) curve analysis of samples showed the area under the ROC curve of 0.81 for miR-21 and area of 0.83 for miR-155. In addition, statistical analysis showed that miR-21 and miR-155 RNAs are significantly detected in the plasma of BC patients compared to healthy specimens (P < 0.05). Circulating miRNAs yielded area under the ROC curve of 0.99 for miR-21 and 0.92 for miR-155. Conclusion: Our data showed that miR-21 and miR-155 oncomiRs can be considered as noninvasive biomarkers for monitoring breast carcinomas. However, further investigations are needed to confirm the use of these noncoding RNAs in pathology.
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Antiproliferative and apoptotic effects of the natural alkaline water (Zamzam) in breast cancer cell line MCF-7 Highly accessed article p. 1098
Shiekhah M Al Zahrani, Ulfat M Omar, Sawsan A Rahimulddin, Ayat B Al-Ghafari, Alia M Aldahlawi, Huda A Al Doghaither
DOI:10.4103/jcrt.JCRT_381_17  PMID:31603117
Background: Zamzam water (ZW) is a natural alkaline water that contains several minerals that may represent a powerful tool for cancer therapy. Objectives: In this research, in vitro antiproliferative and apoptotic effects of ZW were investigated in the human breast cancer cell line MCF-7. Materials and Methods: This study was conducted between January 2015 and February 2016. The effects of ZW on the morphology and the cell viability of human breast cancer cell line MCF-7 were determined. The cell death type and cell cycle changes were investigated using flow cytometry. Finally, reactive oxygen species (ROS) were also measured by fluorometric technique. Results: MCF-7 cells treated with either ZW with adjusted pH at 7.2 or unadjusted pH at 8 showed reduced cell viability of cancerous cells. The cell death occurred through the apoptosis pathway under both treatment conditions. The treated MCF-7 cells were arrested in the G2/M phase and decreased in the G1 phase. Only the unadjusted pH ZW sample demonstrated an increase in the production of both cytoplasmic and mitochondrial ROS in MCF-7 cells. Conclusion: All the results in the present study indicated, for the first time, that ZW might have anticancer and apoptotic effects on breast cancer cell line.
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Anticancer activity of britannin through the downregulation of cyclin D1 and CDK4 in human breast cancer cells p. 1105
Maryam Hamzeloo-Moghadam, Mahmoud Aghaei, Mohammad Hossein Abdolmoham Madi, Faranak Fallahian
DOI:10.4103/jcrt.JCRT_517_17  PMID:31603118
Aim of the Study: Both apoptotic induction and cell cycle blockade in cancer cells are effective strategies to eliminate cancer cells. Many conventional cancer drugs that induce apoptosis and inhibit cell cycle progression have been reported as potential therapeutics for various types of cancer. Britannin is a natural sesquiterpene lactone that its profound anticancer properties were revealed in our previous study. In this study, we evaluated the effects of britannin on the cell cycle distribution and also cell cycle-related proteins. Materials and Methods: Analysis of cell cycle distribution was carried out using flow cytometer. The effects of britannin on cyclin D1 and CDK4 expression were evaluated using the Western blot. Results: The obtained results show that britannin at the low concentrations induces cell growth inhibition mainly through G1-phase arrest while it seems that apoptosis contributes to cell growth inhibitory effect of high doses of britannin. Reduction of cyclin D1 and CDK4 protein levels were also observed after treating cancer cells with britannin. Conclusion: The obtained results reveal that britannin can inhibit MCF-7 and MDA-MB-468 breast cancer cells proliferation through arresting cell cycle progression through cyclin D1/CDK4-mediated pathway.
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Factors that affect the presence of the entire liver incidentally detected by the simulation computed tomography and the detection of inferior border through anthropometric measurement in breast cancer patients p. 1109
Kamuran Ibis
DOI:10.4103/jcrt.JCRT_293_18  PMID:31603119
Objective: The aim was to evaluate the parameters that influence the incidental presence of whole liver detected by simulation computed tomography (simCT) while irradiation in breast cancer patients and to evaluate the factors predicting the presence of the liver in simCT scanning and defining the inferior border in simCT. Subjects and Methods: We analyzed simCT radiotherapy (RT) planning images of 327 patients with breast cancer. During the evaluation, whether the entire liver was included in the simCT scanning and the level of the vertebra where the inferior border of the simCT scan passed were investigated. Left (L) and right (R) lung, L and R breast, and heart volume were recorded so that they would reflect the internal volume of the thorax. From the simCT images, anteroposterior (A-P) distance at the jugular notch level, A-P and R-L lateral distances at manubriosternal joint alignment, A-P and R-L lateral distances at xiphisternal joint alignment were measured. The predictive value of these measurements and volumes on whether the liver was present in simCT were determined by receiver operating characteristic (ROC) curve analysis. Results: The liver was included in 72 (22%) out of 327 simCT scans. ROC analysis was applied to the whole group; bilateral lung volume (P < 0.001), bilateral lung + heart volume (P < 0.001), xiphisternal angle R-L lateral distance (P = 0.009), manubriosternal angle A-P distance (P = 0.49), R breast volume (P = 0.007), and L breast volume (P < 0.001) were associated with the visualization of liver. A total of 37 of 72 patients, whose inferior level of the simCT sections passed below L1, had entire liver visualization. The cutoff value of xiphisternal joint R-L lateral distance was found as 31.55 cm, and its sensitivity and specificity were calculated as 81%, and 60%, respectively. Conclusion: Through R-L lateral measurement taken from the midaxillary line at the level of the xiphisternal joint, we showed that liver would be present in simCT with a sensitivity of 81% at L1 level in those 31.55 cm and above.
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Antitumoral potential of microvesicles extracted from human adipose-derived mesenchymal stem cells on human breast cancer cells p. 1114
Zahra Rezaie, Abdolreza Ardeshirylajimi, Mahmood Dehghani Ashkezari, Seyed Morteza Seifati
DOI:10.4103/jcrt.JCRT_147_18  PMID:31603120
Aim of Study: One of the new methods that have promising results is the use of cell-derived microvesicles (MVs) to kill tumor cells. Given that MVs contain apoptotic materials, genes, and proteins, they can interfere with the fate of adjacent cells. Materials and Methods: In the present study, after adipose tissue-derived mesenchymal stem cells (AT-MSCs) isolation and characterization, MVs were derived from AT-MSCs and then characterized morphologically by standard error of the mean and size determination by DLS, and after that, the influence of MVs on human breast cancer cells (MCF-7) was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay and apoptosis-related gene expression. The raw data were analyzed in SPSS.17 software. Results: The results indicated that MVs have a size range of 500–1500 nm, and the viability of MCF-7 was significantly decreased when treated by different concentrations of MVs and it was confirmed when apoptosis-related genes' expression level was measured by real-time reverse transcription polymerase chain reaction whereas demonstrated that apoptosis genes including Bax, P53, P21, and EP300 (2− ΔΔ CT) and ΔCT values were expressed significantly in MCF-7 treated by MVs higher than those nontreated, and decrease of Bcl-2 expression level in MVs-treated MCF-7 was also significant as an antiapoptosis-related gene. Conclusions: Taking together, AT-MSC-derived MVs demonstrated anticancer or antitumoral properties on MCF-7 cells, and it could also be effective for other types of cancer cells.
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Prospective randomized trial of standard antiemetic therapy with yoga versus standard antiemetic therapy alone for highly emetogenic chemotherapy-induced nausea and vomiting in South Asian population p. 1120
Trupti O Kothari, SL Jakhar, Dhirendra Bothra, Neeti Sharma, HS Kumar, MR Baradia
DOI:10.4103/jcrt.JCRT_860_16  PMID:31603121
Aim/Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing side effects of highly emetogenic chemotherapy regimens. There have been continuous efforts in the direction to control CINV by many investigators. Materials and Methods: Randomly selected patients were those receiving highly emetogenic chemotherapy regimen grouped into yoga and standard antiemetic therapy (n = 50) just before receiving chemotherapy and continued for the following days and other group (n = 50) received only the standard antiemetic agent. Both the groups were assessed, followed for acute and delayed onset of chemotherapy-induced and anticipatory nausea and vomiting using radiation therapy oncology group grading for the same. We also assessed the quality of life of the patient using the Functional Assessment of Cancer Therapy-General questionnaire. Results: The median age group of the patients was 51 years with male:female ratio 2:1, The Eastern Cooperative Oncology Group (ECOG) performance status was 0/1 in 38% of the selected population, while ECOG 2 in 62% of the patients. In yoga arm, insignificant reduction in chemotherapy-induced nausea (90% vs. 78%, P = 0.35) and but significant reduction in vomiting (42% vs. 22%, P =0.01) was observed as compared to the standard antiemetics only arm. There was a significant reduction in Grade 2 and 3 nausea (84% vs. 38% P < 0.01) and vomiting (14% vs. 0% P < 0.01). Quality of life is also significantly improved in the yoga arm, especially in the ECOG 2 performance status. Conclusions: This study concludes that yoga along with standard antiemetic medication should be a part of the management plan for the cancer patients receiving highly emetogenic chemotherapy.
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Association between spiritual intelligence and stress, anxiety, and depression coping styles in patients with cancer receiving chemotherapy in university hospitals of Tehran University of medical science p. 1124
Mahboobeh Safavi, Seyyed Taha Yahyavi, Hamideh Fatehi Narab, Seyyed Hossein Yahyavi
DOI:10.4103/jcrt.JCRT_382_17  PMID:31603122
Background: Holistic care addresses the physical, psychological, social, and spiritual dimensions of the patient in which spiritual dimension plays a pivotal role in patient care. Objective: The objective of this study is to investigate the association between spiritual intelligence with stress, anxiety, and depression coping styles in patients with cancer. Methods: This analytic descriptive study was carried out on 276 patients with cancer receiving chemotherapy in university hospitals of Tehran University of Medical Sciences during 2013–2014. The participants were selected using cluster sampling. Data collection tools included patients' medical history, demographic questionnaire developed by researcher, spiritual intelligence self-report inventory questionnaire, ways of coping questionnaire, and depression, anxiety, and stress scales-42. Pearson correlation and multiple regression analyses were conducted to analyze the data using SPSS 20. Differences were considered significant at the P < 0.05 level. Results: There was inverse significant relationship between spiritual intelligence and stress (r = −0.268 and P < 0.001) and between spiritual intelligence and anxiety (r = −0.200 and P = 0.001) and between spiritual intelligence and depression (r = −0.317 and P = 0.000). There was a significant relationship between spiritual intelligence and coping styles (P < 0.01). The highest association was observed between spiritual intelligence and problem-focused strategy or positive reevaluation strategy (P = 0.000 and r = 0.668 and P = 0.000 and r = 0.667, respectively). Conclusions: Spirituality and religion are an important source of strength for adjusting of patients to cancer and help patients to achieve the sense of meaning and purpose in the course of disease. Implications for Practice: Establishment of settings in hospitals focusing on using spiritual intelligence to improve treatment outcomes in patients with cancer.
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Ligand- and structure-based pharmacophore modeling, docking study reveals 2-[[4-[6-(isopropylamino) pyrimidin-4-yl]-1H-pyrrolo[2,3-b] pyridin-6-yl] amino] ethanol as a potential anticancer agent of CDK9/cyclin T1 kinase p. 1131
Afzal Hussain, Chandan Kumar Verma
DOI:10.4103/jcrt.JCRT_47_18  PMID:31603123
Objective: CDK9/Cyclin T1 kinase is a protein kinase, indirectly involved in the cell cycle progression in the form of transcription elongation, CDK9 specific inhibitors may be a potential alternative treatment not only for cancer but also other life-threatening diseases. Materials and Methods: Ligand-based and structure-based pharmacophore model was developed for discovering of the new anticancer agents. These models used as three-dimensional query for virtual screening against the chemical structure databases such as Maybridge HitFinder, MDPI, and ZINC. Subsequently, the potential hit compound was filtered by the ADMET and docking score. Results: After applying all filtration, 11 hits were found as potential hits based on good docking scores as well as good ADMET properties. Compound 2-[4-[6-(isopropylamino) pyrimidin-4-yl]-1H-pyrrolo[2,3-b] pyridin-6-yl] amino] ethanol was found to be most potent among all the potential hits. These hits could be used as an anticancer agent in near future. Conclusions: So many advances in the treatment of death leading diseases have been made over the past few decades, However, looking for the development in this research ligand-based and structure-based pharmacophore modeling was done, hit1 2-[4-[6-(isopropylamino) pyrimidin-4-yl]-1H-pyrrolo[2,3 b] pyridin-6 yl] amino] ethanol was found to be more potent and selective. It is understandable that these hits could be as selective and potent anticancer agents of cyclin-dependent kinase complex.
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A new acetylacetone derivative inhibits breast cancer by apoptosis induction and angiogenesis inhibition p. 1141
Wamidh H Talib, Mousa Al-Noaimi, Elaf S Alsultan, Raja Bader, Esam Qnais
DOI:10.4103/jcrt.JCRT_948_17  PMID:31603124
Aim: Cancer is one of the main causes of death worldwide. High mortality rates were reported among breast cancer patients which makes the development of new anticancer agents targeting breast cancer a priority. The synthesis of the compounds incorporating– N=N– group is an important field of research that may lead to the discovery of new anticancer drug. Materials and Methods: In this work, we report the synthesis of a compound has O and N centers with the incorporation of the arylazo group (4-BrC6H4–N=N–) into acetylacetone to synthesize 3-(4-Bromo phenylazo)-2,4-pentanedione. Physical characteristics of the newly synthesized compound were determined by measuring electronic absorption spectra, nuclear magnetic resonances, and the infrared absorption spectrum. The inhibitory effect of the compound against breast cancer cell lines was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Its effect on angiogenesis was evaluated by measuring vascular endothelial growth factor (VEGF) levels in treated cells. The ability of the compound to induce apoptosis in cancer cells was tested by measuring caspase-3 activity, and its capacity to stimulate the immune system was evaluated by measuring the levels of interferon gamma (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 cytokines in treated lymphocytes. Results: Significant antiproliferative activity against breast cancer cell lines was observed in treated cells. Low levels of VEGF and high caspase-3 activity were observed in treated cells. Levels of IFN-γ, IL-2, and IL-4 were increased after treating lymphocytes with this compound. Conclusion: 3-(4-Bromo phenylazo)-2,4-pentanedione is a promising anticancer agent that can inhibit breast cancer cells through apoptosis induction and angiogenesis inhibition. Further testing is needed to clearly determine the molecular mechanisms of the anticancer effect of this compound.
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p16 promoter methylation, expression, and its association with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 subtype of breast carcinoma p. 1147
Aditi Goyal, Ram Krishna Sahu, Mohit Kumar, Sonal Sharma, Shariq Qayyum, Navneet Kaur, Usha Rani Singh, Ravi Mehrotra, Suresh Hedau
DOI:10.4103/jcrt.JCRT_472_18  PMID:31603125
Objectives: The purpose of the study is to investigate p16 protein expression and promoter methylation of p16 gene and their association with molecular subtypes based on parameter such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Materials and Methods: A total of 114 breast cancer tissue biopsies were collected for methylation-specific polymerase chain reaction (MSP) and immunohistochemical (IHC) analysis. Results: Seven tissue microarrays were constructed. p16 protein expression was studied in 114 cases, of which 35/114 (30.7%) cases showed strong expression and the majority of them had ER-positive tumor (57.6%), and it was statistically significant (P < 0.0074). Similarly, p16 expression was reduced in the majority of PR-negative tumors (83.9%) and the association was statistically significant (P = 0.0026). p16 methylation was studied in 114 cases and was positive in 71.0% cases. Conclusion: High p16 protein expression was associated with ER-positive, PR-negative, and HER2-negative tumors which is associated with poor prognosis. p16 protein expression may be used as a prognostic indicator to predict treatment response to hormonal therapy.
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The relationship between hopelessness level and complementary and alternative medicine use in patients with breast cancer p. 1155
Mahide Demireloz Akyuz, Nazan Tuna Oran, Ummahan Yucel, Aysun Eksioglu, Yeliz Cakır Kocak
DOI:10.4103/jcrt.JCRT_815_17  PMID:31603126
Introduction: Following the diagnosis and treatment of breast cancer, women may experience some emotions such as anxiety, uncertainty, andhopelessness, and these experiences may vary from person to person. Many patients, along with conventional treatments, can resort to traditional methods to support the treatment, prevent recurrence of cancer, cope with the side effects of the treatment, and strengthen physically and mentally. Aims: The study was aimed at determining the relationship between hopelessness level and use of complementary and alternative medicine (CAM) methods in women with breast cancer. Materials and Methods: In this descriptive and cross-sectional study, 336 women with breast cancer who presented to the mammography unit were contacted. Among the CAM methods used, herbal treatment methods rank first. Of the reasons, women prefer these methods; “CAM provides psychological comfort” takes the first place. Results: The mean scores obtained from the Beck Hopelessness Scale by the women who used and who did not use CAM were 5.45 ± 5.18 and 4.44 ± 4.10, respectively. The difference between the two groups was statistically significant (P < 0.05). Conclusion: In conclusion, women with breast cancer may attempt to use CAM due to hopelessness. Therefore, in the course of medical treatment of patients, CAM practices should be questioned, they should be provided counseling and if necessary, referred for psychological support.
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Aberrant signal transduction in Indian triple-negative breast cancer patients p. 1162
Vasantha Kumar Bhaskara, Chaitra Jayaram, M Priyanga, N H Thilak Nayaka, A Shivakumara, Nagarathna Amaresh, Vijaya V Mysorekar
DOI:10.4103/jcrt.JCRT_803_16  PMID:31603127
Aim of Study: The aim of this study is to correlate the prominin-1 or CD133 association with functional pathway markers of cancer stemness in Indian triple-negative breast cancer (TNBC) patient samples. Materials and Methods: TNBC samples were confirmed for the absence of hormone receptors (estrogen receptor–ER/progesterone receptor) and human epidermal growth factor receptor-2 or proto-oncogene neu or erbB2 or CD340 by immunohistochemical analysis. Formalin-fixed paraffin-embedded samples of patients were used to collect the total RNA. Then, one-step reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the cancer stemness-related transcript levels in the different samples. The RT-PCR products were analyzed semi-quantitatively on agarose gels. The band intensities of respective samples for different transcripts were analyzed by densitometry. Results: TNBC-confirmed samples had shown increased levels of CD133 transcript than control tissues. Further, elevated CD133 transcripts are correlated with higher transcript levels of NOTCH1/FZD7/transforming growth factor-beta receptor Type III R/patched-1 pathway mediators. Conclusions: This work has clearly indicated that there is a correlation between CD133 and functional pathways that control cancer stem cells in TNBC. These observations may indicate the possible association between cancer stemness and TNBC malignancy.
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CORRESPONDENCES Top

Clear cell carcinoma of breast lipid-rich variant p. 1167
Hema Kini, Sriram Bhat, Pooja K Suresh, Minu Thomas
DOI:10.4103/jcrt.JCRT_870_17  PMID:31603128
Clear cell breast carcinomas are one of the rare types of invasive carcinoma of the breast. Among them, lipid-rich variant is still rare comprising <1%. The tumor derives its name from the intracytoplasmic neutral lipid that gives the cytoplasm a vacuolated and foamy appearance. These tumors are usually hormone receptors negative and Her-2 Neu positive. Here, we report a case of lipid-rich breast carcinoma which showed hormone receptor positivity and Her-2 Neu negative.
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Occult breast cancer in a female with benign lesions p. 1170
Francesca Di Chio, Giuseppe Santangelo, Francesco Fiorentino, Anna Simeone, Giuseppe Guglielmi
DOI:10.4103/jcrt.JCRT_329_17  PMID:31603129
Occult breast cancer is a carcinoma discovered by the presence of axillary lymph node metastases without the detection of the primary breast tumor. The incidence of this very rare pathology is 0.3%–1.0%. The limited number of these cases does not allow for the precise management of this rare pathology and often, the breast cancer manifestation can take many years to become obvious. We report the case of a 35-year-old woman who presented to our department for annual breast screening examination, without any symptoms. At the time of visit, there were two right and one left tumefactions; unfixed and palpable. Ultrasonography examination confirmed the lesions to be benign. One year later, a palpable hypoechoic axillary left lesion appeared: a lymph node with doubtful morphology. On cytological examination, a biopsy was performed for the axillary left mass which showed irregular masses of large malignant cells with pleomorphism and mitotic figures that suggested a carcinoma. The management of this case is suggestive for cancer of unknown primary syndrome.
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Adding bit of esthetics with science modification of batwing mastopexy for breast conservation in a young patient with giant fibroadenoma breast p. 1173
H Harish Kumar, N K Faslu Rahman, Rakesh S Ramesh, GC Raghunandan
DOI:10.4103/jcrt.JCRT_818_17  PMID:31603130
A 19-year-old girl presented with a lump in her right breast and with a history of surgery for the similar complaint 3 years back. Ultrasound was suggestive of benign solitary lesion of size 16 cm × 10 cm. Core biopsy was suggestive of phyllodes tumor, and the histopathology report of previous surgery was also suggestive of phyllodes tumor. Wide excision of the tumor and reconstruction was done with batwing mastopexy and with a slight modification of the described technique so that to avoid contralateral reduction mammoplasty in a young unmarried girl. Postoperative histopathology was suggestive of fibroadenoma measuring 15 cm × 8 cm with all margins free of tumor, and it is probably one of the biggest fibroadenomas reported so far. On follow-up, no significant disparity noted between the appearances of both breasts.
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Metastatic breast cancer to bilateral mandibular ramus regions p. 1177
Guldane Magat, Sevgi Ozcan Sener, Hayriye Cetmili
DOI:10.4103/jcrt.JCRT_447_17  PMID:31603131
Metastatic carcinomas to the jaw bones are uncommon and comprise to about 1% of all malignant oral neoplasms. The purpose of this report is to present a rare case of metastatic breast carcinoma to bilateral mandibular ramus regions. The present case report is about a 40-year-old female patient with the complaints of a paresthesia in the right mandibular area of the last month duration. She was referred to our department by her oncologist with the differential diagnosis of osteonecrosis or metastasis. She had undergone modified radical mastectomy for invasive lobular carcinoma of the left breast. Oral cavity examination did not reveal the existence of any ulcer or fistula. Panoramic, cone-beam computed tomography (CBCT), and positron-emission tomography (PET) were used for diagnosing the lesions. In panoramic radiography and CBCT images, there were lytic lesions on the both of right and left coronoid, condyle, and ramus of the mandible. PET results showed us fluoro-2-deoxy-D-glucose uptake in the mandible and vertebrae. On the basis of the patient's medical history and paresthesia of the lower lip and chin, the metastatic disease was highly suspected. The patient was referred to her oncologist for further treatment since it was not amenable to the surgical management. The general dentist or dental specialist should maintain a high level of suspicion while evaluating patients with a history of cancer. Paresthesias of the lower lip and the chin should be considered ominous signs of metastatic disease.
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Rehabilitation of unilateral mastectomy using a hollow breast prosthesis: A clinical case report p. 1181
Vidya K Shenoy, Blessy Susan Bangera, Veena Maria Pinto, Mithun K Upadhya, Kamalaksha K Shenoy, Eugene Rent
DOI:10.4103/jcrt.JCRT_91_17  PMID:31603132
The incidence of breast carcinoma is reportedly the second highest among all carcinomas in Indian women. Depending on the extent of resection, age, general health, and economic condition of the patient, various methods of breast reconstruction using surgery have been reported with success and a superior cosmesis. When the patient is unwilling to opt for surgical reconstruction due to various constraints, an alternative technique must be employed. In such cases, nonsurgical prosthetic reconstruction using maxillofacial silicones is considered the only viable option. This prevents the need for a second surgery and rehabilitates the patient during the decision-making phase for considering a delayed reconstructive surgery. The prosthesis mimics the natural texture, feel, weight, and appearance as its natural counterpart enabling the patient to go about her routine social activities. This case report illustrates an indigenous method of rehabilitation of a unilateral mastectomy case using hollow breast form/prosthesis.
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Synchronous occurrence of lobular breast carcinoma and granulosa cell tumor of ovary mimicking metastatic lobular breast carcinoma p. 1186
Sumaira Qayoom, Malti Kumari, Sameer Gupta, Madhumati Goel
DOI:10.4103/jcrt.JCRT_2_18  PMID:31603133
Breast cancer is one of the main sources of ovarian metastasis. Diffuse sheet of lobular carcinoma cells can strongly mimic granulosa cell tumor (GCT) which itself is a rare ovarian neoplasm constituting <5% of all the ovarian neoplasms. A 55-year-old female presented with a painful lump in the right breast associated with nipple discharge for 4 months, which on radiological and cytological findings was suspicious of an epithelial malignancy. During routine work-up, a solid-cystic lesion in the left ovarian adnexa was identified. The patient underwent right modified radical mastectomy along with left salpingo-oophorectomy. Histopathological and immunohistochemical features confirmed the diagnosis of a synchronous lobular carcinoma breast with GCT ovary. Simultaneous occurrence of Lobular carcinoma breast (LCB) and GCT ovary is extremely rare. Morphologically, these can look similar, raising a suspicion of LCB metastasis to ovary. This is important to differentiate the two for a proper patient management and prognosis.
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LETTERS TO THE EDITOR Top

Neopterin and mini-mental state examination scores in delirium: New insights? p. 1189
Angelique Egberts, Francesco U S. Mattace-Raso
DOI:10.4103/jcrt.JCRT_383_17  PMID:31603134
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Research is pivotal to fight cancer in developing countries p. 1191
Manigreeva Krishnatreya
DOI:10.4103/jcrt.JCRT_402_17  PMID:31603135
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Balance training as a promising intervention for reducing the risk of fall in elderly patients with chemotherapy-induced peripheral neuropathy p. 1192
Hamed Mortazavi
DOI:10.4103/jcrt.JCRT_83_18  PMID:31603136
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Effect of postoperative time for adjuvant radiotherapy in malignant phyllodes tumor: An institutional experience p. 1194
Veenita Yogi, OP Singh
DOI:10.4103/jcrt.JCRT_658_17  PMID:31603137
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ERRATUM Top

Erratum: Abstracts p. 1196

DOI:10.4103/0973-1482.188641  PMID:31603138
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CORRECTED AND REPUBLISHED Top

Corrected and Republished: Abstracts p. 1197

DOI:10.4103/0973-1482.268448  PMID:31603139
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