PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/11727/4810
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Item Significance of liver metastasis volume in breast cancer patients treated with stereotactic body radiotherapy(2021) Oymak, Ezgi; Guler, Ozan Cem; Onal, Cem; 0000-0002-2742-9021; 34477885; AGG-9214-2022; D-5195-2014Purpose This study analyzed the impact of liver metastasis (LM) volume on treatment outcomes in breast cancer (BC) patients treated with stereotactic body radiotherapy (SBRT). Methods This single-institution retrospective analysis included 40 oligometastatic (<= 5 metastases) BC patients with 58 liver metastases treated with SBRT between April 2013 and March 2021. The prognostic factors for local control (LC), overall survival (OS), and progression-free survival (PFS) rates were assessed. Results Median follow-up time was 28.1 months. Isolated and solitary LM were seen in 26 (65%) and 24 (60%) patients, respectively. Median time to disease recurrence was 10.7 months post liver SBRT. The 2-year OS, PFS, and LC rates were 71.4%, 27.5%, and 86.8%, respectively. In univariate analysis, patients with a gross tumor volume (GTV) of <= 6 cc and a planning target volume (PTV) of <= 38 cc demonstrated a significantly better median OS than those with GTV > 6 cc and PTV > 38 cc. In multivariate analysis, the predictive factors for worse OS were GTV > 6 cc (HR = 3.07 [95% CI, 1.14-8.22; p = 0.03]) and PTV > 38 cc (HR = 5.91 [95% CI, 1.92-18.21; p = 0.002]). No significant factor for PFS was found. Only 2 patients experienced rib fracture at 4 and 6 months post treatment, and 1 patient had a grade II duodenal ulcer. Conclusion Liver SBRT is an effective and safe treatment option for oligometastatic BC patients with excellent LC, promising survival, and limited toxicity. Patients with smaller tumors displayed better OS than their counterparts, validating the effectiveness of a local treatment for this group.Item Cardiotoxicity of Trastuzumab Emtansine (T-DM1): A Single-center Experience(2021) Acibuca, Aynur; Sezer, Ahmet; Yilmaz, Mustafa; Sumbul, Ahmet Taner; Demircan, Senol; Muderrisoglu, Ibrahim Haldun; Ozyilkan, Ozgur; 0000-0002-3444-8845; 34898302; ABG-4047-2020Objective New anti-cancer drugs promise to increased survival benefits and reduce adverse events. Trastuzumab emtansine (T-DM1) is a novel anti-human epidermal growth factor receptor 2 agent that has shown minimal cardiotoxicity in clinical trials. However, data on real-life outcomes are required. Methods A retrospective review of our center's medical records was performed, including female patients aged >= 18 years with a diagnosis of metastatic breast cancer who were treated with T-DM1. Descriptive statistics were used to investigate clinical features that could increase the risk of cardiotoxicity. Cardiotoxicity was determined by comparing pre and post-T-DM1 echocardiogram results and was defined as a decrease in the left ventricular ejection fraction (LVEF) >10% to below 55%. Results Data from 41 female patients with a mean age of 52 +/- 11.5 years were evaluated. A significant LVEF decrease (from 59% to 33%) was observed in one patient during T-DM1 treatment. Further investigation showed that this decrease was due to underlying coronary artery disease, and LVEF recovered to the baseline value after coronary revascularization. Conclusion T-DM1 seems to be safe in terms of cardiotoxicity. Real-life data with a larger sample size are still needed to confirm the cardiac safety of T-DM1.Item Kinome-wide RNAi screening for mediators of ABT-199 resistance in breast cancer cells identifies Wee1 as a novel therapeutic target(2021) Aka, Yeliz; Acikbas, Ufuk; Kutuk, Ozgur; 34171479Antiapoptotic and proapoptotic BCL-2 protein family members regulate mitochondrial apoptotic pathway. Small molecule inhibitors of antiapoptotic BCL-2 proteins including BCL-2-specific inhibitor ABT-199 (Venetoclax) are in clinical development. However, the efficiency of ABT-199 as a single agent in solid tumors is limited. We performed a high-throughput RNAi kinome screen targeting 691 kinases to identify potentially targetable kinases to enhance ABT-199 response in breast cancer cells. Our studies identified Wee1 as the primary target kinase to overcome resistance to ABT-199. Depletion of Wee1 by siRNA-mediated knockdown or inhibition of Wee1 by the small molecule Wee1 inhibitor AZD1775 sensitized SKBR3, MDA-MB-468, T47D and CAMA-1 breast cancer cells to ABT-199 along with decreased MCL1. BH3-only proteins PUMA and BIM functionally contribute to apoptosis signaling following co-targeting BCL-2 and Wee1. Suppression of Wee1 function increased mitochondrial cell death priming. Furthermore, we found that Wee1 inhibition altered MCL1 phosphorylation and protein stability, which led to HUWE1-mediated MCL1 degradation. Our findings suggest that Wee1 inhibition can overcome resistance to ABT-199 and provide a rationale for further translational investigation of BCL-2 inhibitor/Wee1 inhibitor combination in breast cancer.Item The effect of the use of the Gail model on breast cancer diagnosis in bi-rads 4A cases(2021) Karakaya, Emre; Erken, Murathan; Turnaoglu, Hale; Sirinoglu, Tugce; Akdur, Aydincan; Kavasoglu, Lara; 0000-0002-0664-5147; 0000-0002-8726-3369; 0000-0002-3592-5092; 0000-0002-3592-5092; 35677495; AAJ-8219-2021; AAA-3068-2021; ABI-7217-2020; CAA-2756-2022Objective: The BI-RADS classification system and the Gail Model are the scoring systems that contribute to the diagnosis of breast cancer. The aim of the study was to determine the contribution of Gail Model to the diagnosis of breast lesions that were radiologically categorized as BI-RADS 4A. Material and Methods: We retrospectively examined the medical records of 320 patients between January 2011 and December 2020 whose lesions had been categorized as BI-RADS 4A. Radiological parameters of breast lesions and clinical parameters according to the Gail Model were collected. The relationship between malignant BI-RADS 4A lesions and radiological and clinical parameters was evaluated. In addition, the effect of the Gail Model on diagnosis in malignant BI-RADS 4A lesions was evaluated. Results: Among radiological features, there were significant differences between lesion size, contour, microcalcification content, echogenicity, and presence of ectasia with respect to the pathological diagnosis (p< 0.05). No significant difference was found between the lesions' pathological diagnosis and the patients' Gail score (p> 0.05). An analysis of the features of the Gail model revealed that there was no significant difference between the age of menarche, age at first live birth, presence of a first-degree relative with breast cancer, and a history of breast biopsy and the pathological diagnosis (p> 0.05). Conclusion: As a conclusion Gail Model does not contribute to the diagnosis of BC, especially in patients with BI-RADS 4A lesions.Item Comparison between body composition parameters and response to neoadjuvant chemotherapy by using pre-treatment PET CT in locally advanced breast cancer(2020) Yirgin, İnci Kizildag; Has, Duygu; Arslan, Gozde; Aydin, Esra Cureoglu; Sari, Murat; Onder, Semen; Yasemin, Sanli; Cabioglu, Neslihan; Karanlik, Hasan; Tukenmez, Mustafa; Dursun, Memduh; Muslumanoglu, Mahmut; Ozmen, Vahit; 33294497Purpose: To compare the adipose and muscle tissue areas in patients who responded differently to neoadjuvant chemotherapy. Methods: One hundred and eighty six patients diagnosed with breast cancer who underwent neoadjuvant chemotherapy between January 2015- October 2019 and were operated after the treatment were retrospectively included in the study. Pathological results were divided into five groups using the Miller-Payne grading systems. Grade 1 indicating no significant reduction in malignant cells; Grade 2: a minor loss of malignant cells (<= 30 %); Grade 3: reduction in malignant cells between 30 % and 90 %; Grade 4: disappearance of malignant cells >90 %; Grade 5: no malignant cells identifiable. Pre-treatment PET CT scans were evaluated, and calculation of body composition parameters were performed on a single axial section passing through the L3 vertebrae. Spearman's correlation test was used to analyze the correlation between SAT, VAT, MT parameters and pathological responses. Results: There was no strong correlation between the 5 groups separated according to neoadjuvant chemotherapy treatment response and tissue distributions. However, that there was a very low correlation found between superficial adipose tissue and pathological response (r=, 156). Conclusion: In conclusion, our results have provided a very low correlation between SAT and more than 30 % response. More research is required to evaluate the role of the body fat and muscle parameters in response to neoadjuvant chemotherapy in larger patient populations.Item The use of 18F-FDG positron emission tomography to detect mediastinal lymph nodes in metastatic breast cancer(2020) Onal, Cem; Findikcioglu, Alper; Guler, Ozan Cem; Reyhan, Mehmet; 0000-0001-6908-3412; 0000-0002-2742-9021; 33125983; AAC-5654-2020; D-5195-2014Background: To assess the predictive value of F-18-fluorodeoxyglucose positron-emission tomography (FDG-PET/CT) in detecting mediastinal lymph node metastasis with histopathologic verification in breast cancer (BC) patients. Materials and methods: Between February 2012 and October 2019, 37 BC patients who underwent histopathological verification for FDG-PET positive mediastinal lymph nodes were retrospectively analyzed. Nine patients (24%) were screened before beginning treatment, while 27 (76%) were screened at the time of disease progression, an average of 39 months after completion of initial treatment. Results: The histopathologic diagnosis revealed lymph node metastasis from BC in 15 patients (40%) and benign disease in 22 patients (60%). The standardized uptake value (SUVmax) of mediastinal lymph nodes was significantly higher in patients with lymph node metastasis compared to those with benign histology (9.0 +/- 3.5 vs. 5.9 +/- 2.4; P = 0.007). The cut-off value of SUVmax after the ROC curve analysis for pathological lymph node metastasis was 6.4. Two of the 15 patients with mediastinal SUVmax <= 6.4 and 13 of the 22 patients with SUVmax > 6.4 had lymph node metastasis. Age and pathological findings were prognostic factors for overall survival in univariate analysis. The treatment decision was changed in 19 patients (51%) after mediastinoscopic evaluation of the entire cohort. Conclusions: This is the first study to support the need for pathologic confirmation of a positive PET/CT result following evaluation of mediastinal lymph nodes for staging BC, either at initial diagnosis or at the time of progression. Treatment decisions were consequently altered for nearly half of the patients. (C) 2020 The Author(s). Published by Elsevier Ltd.Item Associations between the expression of mucins (MUC1, MUC2, MUC5AC and MUC6) and clinicopathologic parameters of human breast carcinomas(2020) Oral, Onur; Unverdi, Hatice; Kumcu, Emrah; Turkbey, Duygu; Dogan, Serdar; Hucumenoglu, Sema; 33154304Aims: The aim of this study is to evaluate the relationships between the expression of mucins in invasive breast carcinomas and clinicopathologic parameters. Materials and Methods: We examined 150 cases of invasive breast carcinoma, using the 2012 World Health Organization (WHO) classification of the tumors of the breast. We studied the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. We also evaluated normal breast tissue and ductal carcinoma in situ (DCIS) lesions in nearby invasive tumor areas. Results: In invasive breast carcinomas, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 98.6%, 11.3%, 9.9, and 8.5% of cases, respectively. MUC2, MUC5AC, and MUC6 were overexpressed in invasive tumors and DCIS lesions were compared with normal breast tissue. The apical pattern of MUC1 was correlated with low grade and ER expression. MUC2 was correlated with mucinous carcinoma and an inverse association with invasive ductal carcinoma, not otherwise specified (NOS). MUC6 expression was associated with lymphovascular invasion. Conclusions: Most invasive breast tumors express MUC1 and the apical pattern of MUC1 is correlated with low grade and ER expression. MUC6 expression is associated with indicators of poor prognosis. Further comprehensive studies need to evaluate the role of mucins as a potential biomarker and to be used as a specific therapeutic target against breast cancer.Item Diffusion-Weighted Imaging of Breast Cancer: Correlation of the Apparent Diffusion Coefficient Value with Pathologic Prognostic Factors(2019) Tezcan, Sehnaz; Uslu, Nihal; Ozturk, Funda Ulu; Akcay, Eda Yilmaz; Tezcaner, Tugan; 31620686; ABC-5258-2020Objective: The aim was to evaluate relationship between apparent diffusion coefficient (ADC) values with pathologic prognostic factors in breast carcinoma (BC). Materials and Methods: 83 patients were enrolled in this study. Prognostic factors included age, tumor size, expression of estrogen receptor (ER) and progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), nuclear grade (NG), lymph node involvement and histologic type. The relationship between ADC and prognostic factors was determined using Independent sample t-test, ANOVA, Pearson correlation and relative operating characteristics (ROC) analysis. Results: There was no significant difference between ADC and prognostic factors, including age, tumor size, ER, HER2 and histologic type. The PR-positive tumors (p=0.03) and axillary lymph node involvement (p=0.000) showed a significant association with lower ADC values. The ADC values were significantly lower in high-grade tumors than low-grade tumors (p=0.000). ROC analysis showed an optimal ADC threshold of 0.66 (x10-3 mm(2)/s) for differentiating low-grade tumors from high-grade tumors (sensitivity, 85.5%; specificity, 81%; area under curve, 0.90). Conclusion: The lower ADC values of BC were significantly associated with positive expression of PR, LN positivity and high-grade tumor. Especially, ADC values were valuable in predicting NG subgroups.Item Radiotherapy After Skin-Sparing Mastectomy and Implant-Based Breast Reconstruction(2019) Sari, Sezin Yuce; Guler, Ozan Cem; Gultekin, Melis; Yildirim, Berna Akkus; Onal, Cem; Ozyigit, Gokhan; Yildiz, Ferah; 0000-0001-6908-3412; 31255547; AAC-5654-2020We aimed to evaluate the cosmetic results of radiotherapy in 170 breast cancer patients after implant-based reconstruction. Cosmetic results were excellent or fair in most patients after radiotherapy. However, bolus use, lymphatic irradiation, and the volume receiving at least 110% of the prescribed dose being >1% significantly deteriorated the outcomes. Introduction: We evaluated the cosmetic results of radiotherapy (RT) after implant-based reconstruction (IBR). Patients and Methods: We retrospectively evaluated 170 patients with 171 breast cancers treated between December 2004 and January 2016 in 2 university hospitals. RT fields were reconstructed breast (RB) only in 24 (14%), and RB and regional lymphatics in 147 (86%) breasts, respectively. All but 1 patient received a total 50 Gy with conventional fractionation. All patients received systemic chemotherapy. One hundred thirty-eight (81%) patients received hormonal therapy; 118 tamoxifen and 20 aromatase inhibitor. Results: Median follow-up time was 46.8 months (range, 1-163 months). The 5-year disease-free and overall survival rate was 83% and 93%, respectively. Cosmetic results were considered excellent in 111 (65%), fair in 46 (27%), and bad in 14 (8%) RB by patients. Thirty-four (20%) RB had restorative surgery; because of surgeons' preference because of implant natural life time span in 5, and contracture, fibrosis, deformation, or dislocation of the implant, or cellulitis in the remaining. Statistically significant adverse factors in univariate analysis for impaired cosmetic outcome were bolus use on the RB, lymphatic irradiation, and volume that received at least 110% of the prescribed dose being >1%. The use of bolus material was the only prognostic factor for deterioration of the cosmetic result in multivariate analysis. Conclusion: RT after IBR yields acceptable cosmetic results. Although only 111 (65%) of RBs were considered to have excellent cosmetic results, only a small percentage of patients needed reoperation because of bad cosmetic outcome. (C) 2019 Elsevier Inc. All rights reserved.Item Determining Breast Cancer Treatment Costs Using the Top Down Cost Approach(2019) Tekin, Rukiye Numanoglu; Saygili, Meltem; 31620683Objective: Breast cancer is the most common type of cancer among women in Turkey, with approximately 15.000 breast cancer diagnoses each year. In this study, our goal was to determine annual direct medical costs of all breast cancer patients in Turkey with top down cost approach. Materials and Methods: Data regarding patients who have been diagnosed with breast cancer and received health services from any hospital in Turkey in 2014 were used for the purpose of the study. Data were obtained from the MEDULA System for a total of 126.664 patient. Treatment of costs of patients were calculated based on types of patient admissions (inpatient/outpatient/intensive care) and costs of drugs and medical equipment. Indirect costs and out of pocket costs were not included. Results: Total medical costs of 126,664 patients was calculated as $116.792.107,9, with an average treatment cost per patient of $922,1. Based on types of patient admission, intensive care treatment had the highest average cost with $2.916.5. In metastatic breast cancer patients, average annual treatment cost per patient is $2.326,6, which is 2.8 times higher compared to non-metastatic breast cancer patients. Conclusion: In order to ensure effective resource allocation at micro and macro level, healthcare administrators have to learn costs of diseases with high incidence such as breast cancer. Results obtained from studies on disease costs calculated using the top down cost approach provide data on actual health services use and therefore are seen as important tools for healthcare administrators in terms of effective resource allocation.