Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item The Effect of Preoperative 18f Fdg-Pet on Staging and Treatment Protocols in Breast Cancer Patients(2021)AIM: We aimed to evaluate the effect of PET taken before surgery on the treatment protocol in patients diagnosed with BC and whether PET resulted in changes in the disease stage. MATERIAL AND METHODS: BC patients in our hospital who underwent surgery between 2016-2020 were retrospectively analyzed. The effect of preoperative PET on the treatment protocol was evaluated in all. Patients were divided into subgroups depending on whether they underwent direct surgery without CTX or were operated on after CTX initiation. In addition, in the group that did not receive CTX, axillary findings of PET were compared with postoperative histopathological results, and axillary PPV, NPV, sensitivity and specificity of PET were determined. In this subgroup, the preoperative PET stage was compared with the postoperative histopathological stage, and any changes in the disease stage were compared. RESULTS: In our study, PET affected the treatment protocol of 19 patients (20%). PET resulted in staging differences in 57.6% overall, increased staging in four patients (8.8%) who did not receive early-stage CT, and lower staging in 22 (48.8%) patients in the group. In early-stage BC of PET, the PPV for axilla was 81.2%, the NPV was 65.5%, sensitivity was 56.5%, and specificity was 86.3%. DISCUSSION: Although PET has many limitations, the determination of the size of the primary tumor and the multiple foci at different locations according to PET findings helped us to easily determine the treatment protocol for patients planned for BCS. CONCLUSION: The preoperative routine use of PET, which can provide more information about metastasis and stage than other methods in patients undergoing BC surgery, may improve the management of treatment in these patients.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 A Functional HOTAIR Rs12826786 C > T Polymorphism Is Associated with Breast Cancer Susceptibility and Poor Clinicopathological Characteristics in A Turkish Population: A Hospital-Based Case-Control Study(2016) Bayram, Suleyman; Sumbul, Ahmet Taner; https://orcid.org/0000-0002-5573-906X; 26577852; D-4793-2014Hox transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is pervasively overexpressed and correlated with tumor invasion, progression, metastasis, and poor prognosis in various human cancers including breast cancer (BC) that plays a role as an oncogenic molecule. A common functional single-nucleotide polymorphism (SNP) (rs12826786 C > T) at the HOTAIR promoter has been reported to influence HOTAIR expression and gastric adenocarcinoma susceptibility, but relation of HOTAIR rs12826786 C > T polymorphism with BC susceptibility and clinicopathological characteristics has yet to be reported. To explore the association of the HOTAIR rs12826786 C > T polymorphism with the risk of BC in a Turkish population, a hospital-based case-control study was carried out consisting of 123 BC patients and 122 age-matched healthy controls. HOTAIR rs12826786 C > T polymorphism was determined by real-time polymerase chain reaction (PCR) using TaqMan assay. We found that women carrying TT genotype of HOTAIR rs12826786 C > T polymorphism had an increased risk of developing BC in both codominant (odds ratio (OR) = 2.24, 95 % confidence interval (CI) 1.05-4.81, P = 0.02) and recessive (OR = 2.49, 95 % CI 1.25-4.97, P = 0.008) inheritance models. Moreover, TT genotype of HOTAIR rs12826786 C > T polymorphism was significantly related with multiple clinicopathological characteristics concerned with worse BC progression such as advanced TNM stage (III and IV), larger tumor size (T3 and T4), and distant metastasis (M1), as well as poor histological grade (III) (P < 0.05). Because of our results put forward for the first time that TT genotype of HOTAIR rs12826786 C > T polymorphism might play crucial roles in genetic susceptibility and poor prognosis for BC in Turkish population, further independent studies are needed to confirm our results in a larger series, as well as in patients of distinct populations.Item Distinct Apoptotic Blocks Mediate Resistance to Panher Inhibitors in HER2+Breast Cancer Cells(2018) Karakas, Bahriye; Ozmay, Yeliz; Basaga, Huveyda; Gul, Ozgur; Kutuk, Ozgur; https://orcid.org/0000-0001-9854-7220; 29733883; AAH-1671-2019Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells. Cells were also cross-resistant to dacomitinib. BH3 profiles of HER2 + breast cancer cells efficiently predicted antiapoptotic protein dependence and development of resistance to panHER inhibitors. Reactivation of ERK1/2 was primarily responsible for acquired resistance in SKBR3 and ZR-75-30 cells. Adding specific ERK1/2 inhibitor SCH772984 to neratinib or dacomitinib led to increased apoptotic response in neratinib-resistant SKBR3 and ZR75-30 cells, but we did not detect a similar response in neratinib-resistant BT474 cells. Accordingly, suppression of BCL-2/BCL-XL by ABT-737 was required in addition to ERK1/2 inhibition for neratinib- or dacomitinib-induced apoptosis in neratinib-resistant BT474 cells. Our results showed that different mitochondrial apoptotic blocks mediated acquired panHER inhibitor resistance in HER2 + breast cancer cell lines as well as highlighted the potential of BH3 profiling assay in prediction of panHER inhibitor resistance in breast cancer cells.Item Stromal Podoplanin Expression And Its Clinicopathological Role in Breast Carcinoma(2018) 30173230Introduction: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression. One of the differently expressed molecules recently found is podoplanin. Podoplanin, utilised as a lymphatic endothelial marker, is found to be expressed in CAFs. The aim of this study is to evaluate the relationship between the stromal expression of podoplanin in invasive breast carcinoma and clinicopathological parameters. Materials & Methods: Podoplanin expression was evaluated immunohistochemically in 153 breast cancers. Tumours with >= 10% distinct cytoplasmic podoplanin staining in CAFs were considered as positive. Results: In 65.3% of analysed tumours, podoplanin expression was found positive in CAFs. According to our results, podoplanin positive CAFs correlated significantly with tumour size (p=0.012), tumour grade (p=0.032) and cerbB2 score (p=0.032). Discussion: Our results suggest that podoplanin expression by CAFs could predict poor patient outcome in breast carcinoma.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.
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