Araştırma Çıktıları
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Item Impact of Oncotype DX Recurrence Score on Treatment Decisions: Results of a Prospective Multicenter Study in Turkey(CUREUS INC, 2016-01-01) Ozmen, Vahit; Atasoy, Ajlan; Gokmen, Erhan; Ozdogan, Mustafa; Guler, Nilufer; Uras, Cihan; Ok, Engin; Demircan, Orhan; Isikdogan, Abdurrahman; Saip, PinarIntroduction: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX (R) 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the impact of the Recurrence Score (R) (RS) on treatment decisions and physician perceptions in Turkey. We also studied correlations between RS and routine risk factors. Patients and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at multidisciplinary tumor conferences. The initial treatment decision was recorded before tumor blocks were sent to the central laboratory. Each case was brought back to tumor conference after receiving the RS result. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classical risk factors were evaluated using univariate and multivariate analyses. Results: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of 165 patients, 57\% had low RS, 35\% had intermediate RS, and 8\% had high RS, respectively. The overall rate of change in treatment decision was 33\%. Initially, chemotherapy followed by hormonal therapy (CT+HT) was recommended to 92 (56\%) of all patients, which decreased to 61 (37\%) patients post-RS assay (p<0.001). Multivariate analysis indicated that progesterone receptor (PR) and Ki-67 scores were significantly related to RS. Conclusion: Oncotype DX testing may provide meaningful additional information in carefully selected patients.Item The Outcome of Patients with Triple Negative Breast Cancer: The Turkish Oncology Group Experience(AVES, 2014-01-01) Eralp, Yesim; Kilic, Leyla; Alco, Gul; Basaran, Gul; Dogan, Mutlu; Dincol, Dilek; Demirci, Senem; Icli, Fikri; Onur, Handan; Saip, Pinar; Haydaroglu, AyferObjective:Triple negative breast cancer (TNBC) is generally considered as a poorer prognostic subgroup, with propensity for earlier relapse and visceral involvement. The aim of this study is to evaluate the outcome of non-metastatic TNBC patients from different centers in Turkey and identify clinical and pathologic variables that may effect survival. Materials and Methods:Between 1993-2007, from five different centers in Turkey, 316 nonmetastatic triple negative breast cancer patients were identified with follow-up of at least 12 months. The data was collected retrospectively from patient charts. The prognostic impact of several clinical variables were evaluated by the Kaplan-Meier and Cox multivariate anayses. Results:Mean age at diagnosis was 49 years (range:24-82). The majority of the patient group had invasive ductal carcinoma (n:260, 82.3\%) and stage II disease (n:164Item Turkish national consensus on breast cancer management during temporary state of emergency due to COVID-19 outbreak(TURKISH SURGICAL ASSOC, 2020-01-01) Sezer, Atakan; Cicin, Irfan; Cakmak, Guldeniz Karadeniz; Gurdal, Sibel Ozkan; Basaran, Gul; Oyan, Basak; Eralp, Yesim; Gulluoglu, Bahadir M.; Speci, Turkish Natl Breast OncologyObjective: Cancer care is excessively influenced by the COVID-19 outbreak for various reasons. One of the major concerns is the tendency for delayed surgical treatment of breast cancer patients. The outbreak has urged clinicians to find alternative treatments until surgery is deemed to be feasible and safe. Here in this paper, we report the results of a consensus procedure which aimed to provide an expert opinion-led guideline for breast cancer management during the COVID-19 outbreak in Turkey. Material and Methods: We used the Delphi method with a 9-scale Likert scale on two rounds of voting from 51 experienced surgeons and medical oncologists who had the necessary skills and experience in breast cancer management. Voting was done electronically in which a questionnaire-formatted form was used. Results: Overall, 46 statements on 28 different case scenarios were voted. In the first round, 37 statements reached a consensus as either endorsement or rejection, nine were put into voting in the second round since they did not reach the necessary decision threshold. At the end of two rounds, for 14 cases scenarios, a statement was endorsed as a recommendation for each.Thirty-two statements for the remaining 14 were rejected. Conclusion:There was a general consensus for administering neoadjuvant systemic therapy in patients with node-negative, small-size triple negative, HER2-positive and luminal A-like tumors until conditions are improved for due surgical treatment. Panelists also reached a consensus to extend the systemic treatment for patients with HER2-positive and luminal B-like tumors who had clinical complete response after neoadjuvant systemic therapy.Item Diagnostic Performance of AI for Cancers Registered in A Mammography Screening Program: A Retrospective Analysis(SAGE PUBLICATIONS INC, 2022-01-01) Kizildag Yirgin, Inci; Koyluoglu, Yilmaz Onat; Seker, Mustafa Ege; Ozkan Gurdal, Sibel; Ozaydin, Ayse Nilufer; Ozcinar, Beyza; Cabioglu, Neslihan; Ozmen, Vahit; Aribal, ErkinPurpose: To evaluate the performance of an artificial intelligence (AI) algorithm in a simulated screening setting and its effectiveness in detecting missed and interval cancers. Methods: Digital mammograms were collected from Bahcesehir Mammographic Screening Program which is the first organized, population-based, 10-year (2009-2019) screening program in Turkey. In total, 211 mammograms were extracted from the archive of the screening program in this retrospective study. One hundred ten of them were diagnosed as breast cancer (74 screen-detected, 27 interval, 9 missed), 101 of them were negative mammograms with a follow-up for at least 24 months. Cancer detection rates of radiologists in the screening program were compared with an AI system. Three different mammography assessment methods were used: (1) 2 radiologists' assessment at screening center, (2) AI assessment based on the established risk score threshold, (3) a hypothetical radiologist and AI team-up in which AI was considered to be the third reader. Results: Area under curve was 0.853 (95\% CI = 0.801-0.905) and the cut-off value for risk score was 34.5\% with a sensitivity of 72.8\% and a specificity of 88.3\% for AI cancer detection in ROC analysis. Cancer detection rates were 67.3\% for radiologists, 72.7\% for AI, and 83.6\% for radiologist and AI team-up. AI detected 72.7\% of all cancers on its own, of which 77.5\% were screen-detected, 15\% were interval cancers, and 7.5\% were missed cancers. Conclusion: AI may potentially enhance the capacity of breast cancer screening programs by increasing cancer detection rates and decreasing false-negative evaluations.Item Temporary Implant Irradiation: Survey of Turkish Society of Radiation Oncology Breast Cancer Study Group(GALENOS YAYINCILIK, 2021-01-01) Kaydihan, Nuri; Alco, Gul; Senocak, Mustafa Sukru; Bese, NuranObjective: To understand the clinical approach of radiation oncologists during the treatment of patients with breast reconstruction. Materials and Methods: A questionnaire survey was emailed to 105 active members of the Turkish Radiation Oncology Society, the Breast Cancer Study Group. The factors associated with radiation oncologists and their current practice was identified. Results: Fifty radiation oncologists (47.6\%) responded, and most of the responders (83\%) were physicians who treated >50 new breast cancer patients annually. The majority of the physicians worked in academic hospitals and had more than 15 years of work experience. The early reconstruction rate was noted to be low among patients with mastectomy (<10\% of the mastectomy patients) (p<0.05). Early implant irradiation with temporary tissue expander was noted to be a more common procedure. The majority of the respondents (68\%) preferred to irradiate an inflated implant (20\% total, 80\% partial). In addition, 22\% of the physicians declared that they routinely used bolus and that 60\% of them used it only for patients at a high risk of local recurrence factors. Conclusion: It can thus be concluded that variations exist between experienced radiation oncologists and others. Hypofractionation is not yet commonly practiced for patients with reconstruction in Turkey. A concrete consensus can be helpful to create a homogeneity in treatment decisions and practical applications.Item Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients(ISTANBUL UNIV, FAC PHARMACY, 2019-01-01) Yuksel, Merve Kurtan; Ozturk, Dilek; Oztas, Ezgi; Ozhan, Gul; Turker, Aylin Altanlar; Korkmaz, Taner; Okyar, Alper; Kara, Zeliha PalaCapecitabine is an oral prodrug and converted to 5-fluorouracil using three-step enzymatic pathways which include carboxylesterase (CES). Interindividual differences in the activities of drug-metabolizing enzymes may affect efficacy and toxicity. The aim of this study is to evaluate the association of Single nucleotide polymorphisms (SNP) in CES1 with the pharmacokinetic and adverse effects of capecitabine. Plasma samples were obtained from 7 breast and colorectal cancer patients who were treated with capecitabine-based chemotherapy (1000-1250 mg/m(2)) at 0.5, 1, 2, 3 and 4 hours following drug administration on their first day of the first cycle. The plasma concentrations of the capecitabine were determined by using a high-pressure liquid chromatography-UV detector. SNP (rs8192950) was genotyped using the reverse transcription-polymerase chain reaction. Patients were found to have heterozygote (57\%), wild (29\%), and mutant (14\%) distributions of genotypes (p=0.909). The mean plasma area under the curve (AUC(0-4h)) was 4.60 +/- 2.25 mu g.h/mL, and maximum plasma concentration (C-max) was 3.19 +/- 2.5 mu g/mL. There were no statistically significant differences between genotypes and AUC values (p=0.2236) and the most frequently observed side effects were diarrhea (p=0.1028), asthenia (p=0.6456), anemia (p=0.6456), emesis (p=0.3499). This is the first study evaluating an association of genetic variation in CES1 (rs8192950) with pharmacokinetic and adverse effects of capecitabine. Therefore, additional study in larger groups of patients is required to support our study.Item SAFE: A Novel Microwave Imaging System Design for Breast Cancer Screening and Early Detection-Clinical Evaluation(MDPI, 2021-01-01) Janjic, Aleksandar; Cayoren, Mehmet; Akduman, Ibrahim; Yilmaz, Tuba; Onemli, Emre; Bugdayci, Onur; Aribal, Mustafa ErkinSAFE (Scan and Find Early) is a novel microwave imaging device intended for breast cancer screening and early detection. SAFE is based on the use of harmless electromagnetic waves and can provide relevant initial diagnostic information without resorting to X-rays. Because of SAFE's harmless effect on organic tissue, imaging can be performed repeatedly. In addition, the scanning process itself is not painful since breast compression is not required. Because of the absence of physical compression, SAFE can also detect tumors that are close to the thoracic wall. A total number of 115 patients underwent the SAFE scanning procedure, and the resultant images were compared with available magnetic resonance (MR), ultrasound, and mammography images in order to determine the correct detection rate. A sensitivity of 63\% was achieved. Breast size influenced overall sensitivity, as sensitivity was lower in smaller breasts (51\%) compared to larger ones (74\%). Even though this is only a preliminary study, the results show promising concordance with clinical reports, thus encouraging further SAFE clinical studies.Item CYP19A1 Genetic Polymorphisms rs4646 and Osteoporosis in Patients Treated with Aromatase Inhibitor-Based Adjuvant Therapy(AVES, 2016-01-01) Mazzuca, Federica; Botticelli, Andrea; Mazzotti, Eva; La Torre, Marco; Borro, Marina; Marchetti, Luca; Maddalena, Chiara; Gentile, Giovanna; Simmaco, Maurizio; Marchetti, PaoloObjective: Third-generation aromatase inhibitors (AI) are potent suppressors of aromatase activity. The aim of this study was to measure the incidence of adverse effects in breast cancer patients treated with AI-based adjuvant therapy and the relationship with the CYP19A1 genotypes. Materials and Methods: Forty-five postmenopausal breast cancer patients (46-85 yrs) in AI adjuvant treatment were genotyped for the rs4646 polymorphisms of CYP19A1 gene and three variations were identified. Toxicities were registered at each follow-up medical examination, and classified in accord with the Common Terminology Criteria for Adverse Events. Results: Twenty-four (53.3\%) patients presented the GG genotypeItem A Cell Culture Chip with Transparent, Micropillar-Decorated Bottom for Live Cell Imaging and Screening of Breast Cancer Cells(MDPI, 2022-01-01) Ermis, Menekse; Antmen, Ezgi; Kuren, Ozgur; Demirci, Utkan; Hasirci, VasifIn the recent years, microfabrication technologies have been widely used in cell biology, tissue engineering, and regenerative medicine studies. Today, the implementation of microfabricated devices in cancer research is frequent and advantageous because it enables the study of cancer cells in controlled microenvironments provided by the microchips. Breast cancer is one of the most common cancers in women, and the way breast cancer cells interact with their physical microenvironment is still under investigation. In this study, we developed a transparent cell culture chip (Ch-Pattern) with a micropillar-decorated bottom that makes live imaging and monitoring of the metabolic, proliferative, apoptotic, and morphological behavior of breast cancer cells possible. The reason for the use of micropatterned surfaces is because cancer cells deform and lose their shape and acto-myosin integrity on micropatterned substrates, and this allows the quantification of the changes in morphology and through that identification of the cancerous cells. In the last decade, cancer cells were studied on micropatterned substrates of varying sizes and with a variety of biomaterials. These studies were conducted using conventional cell culture plates carrying patterned films. In the present study, cell culture protocols were conducted in the clear-bottom micropatterned chip. This approach adds significantly to the current knowledge and applications by enabling low-volume and high-throughput processing of the cell behavior, especially the cell-micropattern interactions. In this study, two different breast cancer cell lines, MDA-MB-231 and MCF-7, were used. MDA-MB-231 cells are invasive and metastatic, while MCF-7 cells are not metastatic. The nuclei of these two cell types deformed to distinctly different levels on the micropatterns, had different metabolic and proliferation rates, and their cell cycles were affected. The Ch-Pattern chips developed in this study proved to have significant advantages when used in the biological analysis of live cells and highly beneficial in the study of screening breast cancer cell-substrate interactions in vitro.Item Micropatterned Surfaces Expose the Coupling between Actin Cytoskeleton-Lamin/Nesprin and Nuclear Deformability of Breast Cancer Cells with Different Malignancies(WILEY-V C H VERLAG GMBH, 2021-01-01) Antmen, Ezgi; Demirci, Utkan; Hasirci, VasifMechanotransduction proteins transfer mechanical stimuli through nucleo-cytoskeletal coupling and affect the nuclear morphology of cancer cells. However, the contribution of actin filament integrity has never been studied directly. It is hypothesized that differences in nuclear deformability of cancer cells are influenced by the integrity of actin filaments. In this study, transparent micropatterned surfaces as simple tools to screen cytoskeletal and nuclear distortions are presented. Surfaces decorated with micropillars are used to culture and image breast cancer cells and quantify their deformation using shape descriptors (circularity, area, perimeter). Using two drugs (cytochalasin D and jasplakinolide), actin filaments are disrupted. Deformation of cells on micropillars is decreased upon drug treatment as shown by increased circularity. However, the effect is much smaller on benign MCF10A than on malignant MCF7 and MDAMB231 cells. On micropatterned surfaces, molecular analysis shows that Lamin A/C and Nesprin-2 expressions decreased but, after drug treatment, increased in malignant cells but not in benign cells. These findings suggest that Lamin A/C, Nesprin-2 and actin filaments are critical in mechanotransduction of cancer cells. Consequently, transparent micropatterned surfaces can be used as image analysis platforms to provide robust, high throughput measurements of nuclear deformability of cancer cells, including the effect of cytoskeletal elements.