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 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 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 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.