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Item Treatment Outcomes of Breast Cancer Liver Metastasis Treated with Stereotactic Body Radiotherapy(2018) Onal, Cem; Guler, Ozan Cem; Yildirim, Berna Akkus; https://orcid.org/0000-0002-2742-9021; https://orcid.org/0000-0001-6908-3412; https://orcid.org/0000-0001-6661-4185; 30296648; HOC-5611-2023; AAC-5654-2020; V-5717-2017Background: To assess the outcomes of breast cancer liver metastasis (BCLM) treated with stereotactic body radiotherapy (SBRT) and systemic treatment. Materials and methods: Patients with oligometastasis at the time of liver metastasis (LM) or who became oligometastatic (<= 5 metastases) after systemic treatment were assessed. Twenty-nine liver metastatic lesions were treated with a total of 54 Gy delivered in 3 fractions. The local control (LC), overall survival (OS), and progression-free survival (PFS) rates were calculated using Kaplan-Meier analyses. Results: A total of 22 patients with 29 liver metastatic lesions treated with liver SBRT between April 2013 and September 2017 were retrospectively analyzed. After a median follow-up time of 16.0 months (range 4.4-59.4 months), 18 patients (82%) had disease recurrence, median of 7.4 months (range 1.0-27.9 months) after completion of liver SBRT. The 1- and 2-year OS rates were 85% and 57%, and the 1- and 2-year PFS rates were 38% and 8%, respectively. The 1- and 2-year LC rates were 100% and 88%, respectively. No significant prognostic factors, including disease extension, size of metastasis, number of liver metastasis and timing of liver metastasis, hormonal status affecting OS, PFS and LC were found. No patients experienced Grade 4 or 5 toxicity; furthermore, only one patient experienced rib fracture 6 months after completion of treatment, and one patient had a duodenal ulcer. Conclusion: This study is the first to evaluate the feasibility of SBRT to BCLM patients. Liver SBRT is a conservative approach with excellent LC and limited toxicities. (C) 2018 Elsevier Ltd. All rights reserved.Item Association of Tumor Strain Ratio with Prognostic Factors in Invasive Breast Cancer(2022) Karan, Belgin; Purbager, Aysin; https://orcid.org/0000-0002-7034-7806We evaluate the correlations between tumor strain ratio value and prognostic factors for breast cancers. Fifty-seven women with invasive breast cancer underwent ultrasound elastography prior to surgery. Elastography strain ratio (SR), defined as the fat-to-lesion ratio, was recorded for each lesion using the software in the ultrasound equipment. We evaluated the associations between tumor SR and pathological prognostic factors such as tumor subtype, tumor size, axillary lymph node metastasis, histological grade, vascular invasion, and hormonal receptor status. We found a significant correlation between tumor SR and progesterone receptor (PR) status (p = 0.02). Tumors with axillary lymph node metastasis had a higher SR value than those without lymph node metastasis; however, this difference was not significant. Strain elastography revealed that grade 3 tumors had softer tissues than grade 1 and 2 tumors, although this was not statistically significant. The tumor SR value was not significantly correlated with tumor subtypes, tumor size, vascular invasion, and estrogen receptor or cell surface human epidermal growth factor 2 status (p > 0.05). The present study demonstrated no significant correlation between SR values and prognostic factors, except for PR status. However, tumors with LN metastasis tended to exhibit greater stiffness, and higher grade tumors exhibited lower stiffness owing to necrosis. Further studies with large study population on tumor-associated stiffness are required.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 The Comparison of Helical-IMRT, Direct-IMRT and 3D Radiotherapy Modalities in Breast Radiotherapy Planning(2020) Erdis, Eda; Yucel, Birsen; Ozyurek, Betul; Bozca, RecepOBJECTIVE This study aims to compare dosimetric 3D-CRT, Tomo-helical mu and Direct IMRT methods in intact breast irradiation. METHODS Radiotherapy was planned with three different techniques simulated images of 30 breast cancer patients with negative lymph nodes who underwent breast-conserving surgery. RESULTS The maximum and minimum doses, homogeneity and conformity index and cold-zone volumes were found to be different in all three techniques (p<0.001). The PTV boost maximum doses and homogeneity index were found to be different (p<0.001). The maximum non-PTV dose (110% volume) and the hot zone volumes grasped by these doses, the V5 volume of the body and V5 volumes, outer of PTV were found to be statistically significant for all three techniques (p<0.001). A statistically significant difference was found between the three techniques concerning the ipsilateral lung V5 and V20 volumes, the contralateral lung V5 and V10 volumes and the counter breast maximum and mean doses (p<0.001). The mean and V10 volume of the heart was statistically significant (p<0.001), while the left breast irradiation and mean values were not statistically significant between the three techniques (p=0.529). However, there was a statistically significant difference in the V10 volume of the left breast irradiation between the three techniques (p=0.033). CONCLUSION According to 3D-CRT, it is possible to achieve better dose distribution and dose homogeneity with Tomo-helical and direct IMRT. Low dose volumes arc high with tomo-helical IMRT. Torno-helical IMRT planning provides better ipsilateral lung and heart doses but causes an increase in heart dose/contralatcral breast and for right breast irradiation causes an increase in heart doseItem 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 The Role of Selvester Score on 12-Lead ECG in Determination of Left Ventricular Systolic Dysfunction Among Patients Receiving Trastuzumab Therapy(2019) Ciftci, Orcun; Yilmaz, Kerem Can; Karacaglar, Emir; Akgun, Arzu Neslihan; Yilmaz, Mustafa; Oguz, Arzu; Muderrisoglu, Ibrahim Haldun; 0000-0001-8926-9142; 0000-0001-6512-6534; W-5233-2018; W-8004-2019; ABI-6723-2020Objective: Breast cancer is the most common cancer in women. Trastuzumab is an effective breast cancer agent. The most significant side effect of trastuzumab is left ventricular systolic dysfunction. Selvester score calculated from 12-lead electrocardiography (ECG) has a proven accuracy in predicting left ventricular infarct area and scar volume. We aimed to determine its role in detection of left ventricular systolic dysfunction among trastuzumab-treated breast cancer patients. Methods: A total of 60 trastuzumab-treated patients were retrospectively included. The patients were grouped into two groups with trastuzumab-induced left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) <55%) (Group 1) and without (Group 2). The left ventricular systolic dysfunction group was divided into two subgroups: LVEF <50% and (Group 1a) and LVEF 50-54% (Group 1b). The Selvester score was compared between Group 1 and Group 2, and between Group 1a, Group 1b, and Group 2. The predictive role of Selvester score in trastuzumab-induced left ventricular systolic dysfunction was determined with univariate and multivariate analysis. Results: The mean age of the patients was 56.7 +/- 13.7 years. Twenty (21.1%) patients had trastuzumab-induced left ventricular systolic dysfunction. The Selvester score was similar between Group 1 and Group 2. Group 1a had a significantly greater Selvester score compared to Group 1b and Group 2 (p<0.05); however, Group 1b and Group 2 had similar Selvester scores (p>0.05). The Selvester score was significantly correlated with left ventricular systolic dysfunction in univariate analysis (r=0.189, p<0.05) but not in multivariate analysis. Conclusion: Selvester score may be useful especially for detecting severe trastuzumab-induced left ventricular systolic dysfunction.
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