Publications by authors named "Yesim Eralp"

54 Publications

TIM3 expression on TILs is associated with poor response to neoadjuvant chemotherapy in patients with locally advanced triple-negative breast cancer.

BMC Cancer 2021 Apr 6;21(1):357. Epub 2021 Apr 6.

Department of General Surgery, Istanbul Medical Faculty, Breast Surgery Service, Istanbul University, Istanbul, Turkey.

Background: The expression of immune checkpoint receptors (ICRs) on tumor-infiltrating lymphocytes (TILs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC).

Methods: Expressions of ICRs were examined immunohistochemically in surgical specimens (n = 61) using monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, and CTLA-4. Positivity was defined as staining > 1% on TILs.

Results: The median age was 49 (24-76) years. The majority of patients were clinically T3-4 (n = 31, 50.8%) and clinically N1-3 (n = 58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas PD1, PDL-1, LAG3, and TIM-3 expressions on TILs were 62.3, 50.9, 26.2, and 68.9%. A high expression of CTLA-4 was found to be associated with a better chemotherapy response (OR = 7.94, 95% CI: 0.9-70.12, p = 0.06), whereas TIM-3 positivity was contrarily associated with a worse chemotherapy response (OR = 0.253, 95% CI: 0.066-0.974, p = 0.047) as measured by the MDACC Residual Cancer Burden Index. At a 47-month follow-up, ypN0 (DFS; HR = 0.31, 95% CI: 0.12-0.83, p = 0.02 and DSS; HR = 0.21, 95% CI: 0.07-0.62, p = 0.005) and CTLA-4 high expression on TILs (DFS; HR = 0.38, 95% CI: 0.17-0.85, p = 0.019 and DSS; HR = 0.34, 95% CI: 0.15-0.78, p = 0.01) were found to be associated with improved survival.

Conclusions: These findings demonstrate that CTLA-4, PD-1, PDL-1, and TIM-3 were highly expressed in TNBC. Based on these high expression patterns, further studies directed towards combined therapies are warranted in advanced TNBC in future.
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http://dx.doi.org/10.1186/s12885-021-08054-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025357PMC
April 2021

Turkish national consensus on breast cancer management during temporary state of emergency due to COVID-19 outbreak.

Turk J Surg 2020 Jun 6;36(2):147-163. Epub 2020 May 6.

 SENATURK Senology Academy-Turkey, Istanbul, Turkey.

Objectives: 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.
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http://dx.doi.org/10.5578/turkjsurg.4815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515641PMC
June 2020

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Lung Cancer 2020 10 27;148:48-54. Epub 2020 Jul 27.

Dokuz Eylul University Faculty of Medicine, Department of Medical Oncology, Izmir, Turkey.

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib.

Methods: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria.

Results: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ± 1.6 months and median overall survival (mOS) was 89.1 ± 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ± 2.5 months and mOS of 90.3 ± 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients.

Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ± 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ± 24 months is unprecedented for ROS1(+) NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2020.07.022DOI Listing
October 2020

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Balkan Med J 2020 02 23;37(2):104-107. Epub 2020 Jan 23.

Department of Medical Oncology, Acıbadem University, İstanbul, Turkey

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood.

Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed.

Study Design: Multicenter retrospective observational cohort study.

Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer.

Results: The median progression-free survival in our population was 7 months (25-75 percentile, 4-10), and the median overall survival was 11 months (25-75 percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%).

Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.
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http://dx.doi.org/10.4274/balkanmedj.galenos.2020.2019.11.143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094190PMC
February 2020

Clinical feasibility of NGS liquid biopsy analysis in NSCLC patients.

PLoS One 2019 20;14(12):e0226853. Epub 2019 Dec 20.

GeneKor MSA, Athens, Greece.

Background: Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of "liquid biopsy" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy.

Methods: Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms.

Results: At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients.

Conclusions: This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226853PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924668PMC
April 2020

Prognostic Significance of Adjuvant Chemotherapy Induced Amenorrhea in Luminal A and B Subtypes.

Eur J Breast Health 2018 Jul 1;14(3):173-179. Epub 2018 Jul 1.

Department of Medical Oncology, Istanbul University School of Medicine, İstanbul, Turkey.

Objective: In this retrospective study, chemotherapy induced amenorrhea in patients with early stage breast cancer and its effects on survival were investigated.

Materials And Methods: Two hundred fifty-two patients received adjuvant chemotherapy without ovarian suppression treatment (OST) from 600 premenopausal patients were included in the study. Patients were divided into two groups; with amenorrhea and without, and compared with clinicopathologic features and survival. SPSS version 17 was used.

Results: Chemotherapy-induced amenorrhea (CIA) was observed in 145 (57.5%) of 252 patients who received no OST during follow-up. The 5-year OS rate of patients with CIA was significantly higher than patients without CIA (p= 0.042, 95.9% vs. 89.7% vs. 158.88 vs. 135.33 months, respectively). In the subgroup analysis, the OS in patients with hormone receptor (+) was significantly higher than in those receptor (-) in patients with CIA (p=0.011, 97.5% vs. 90.9% vs. 162.13 vs. 126.16 months, respectively). The OS was significantly longer in the luminal A molecular subtype than in those with luminal B molecular subtype, in patients with CIA, but the difference was not significant in patients without CIA (p=0.027 vs. p=0.074, respectively).

Conclusion: As a conclusion; survival advantage of the chemotherapy induced amenorrhea more pronounced with hormone receptor positivity, lymph node involvement, and advanced disease over patients who do not develop amenorrhea. This advantage of amenorrhea development further prolongs survival compared with luminal B in the luminal A molecular subtype.
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http://dx.doi.org/10.5152/ejbh.2018.3808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092153PMC
July 2018

Impact of Personality Traits, Anxiety, Depression and Hopelessness Levels on Quality of Life in the Patients with Breast Cancer.

Eur J Breast Health 2018 Apr 1;14(2):105-111. Epub 2018 Apr 1.

Department of General Surgery, İstanbul University School of Medicine, İstanbul, Turkey.

Objective: The aim of this study was to investigate the impacts of personality traits, anxiety, depression and hopelessness levels on quality of life in the patients with breast cancer.

Materials And Methods: The study was performed on 90 patients diagnosed with breast cancer and 90 healthy women. Sociodemographic and Clinical Data Collection Form designed by us, Beck Hopelessness Scale (BHS), Beck Anxiety Scale (BAS), Beck Depression Scale (BDS), Eysenck Personality Inventory (EPI) and Quality of Life Scale-Short Form (SF-36) were administered to patients and to control group.

Results: The patients with breast cancer were found to indicate higher levels of anxiety and depression, lower levels of quality of life, and higher scores of personality inventory subscales as compared to the healthy control group. In the patient group, it was identified that the quality of life subscale scores were found to be negatively correlated with anxiety, depression, hopelessness and neurotic personality scores; there was a positive correlation between neurotic personality scores and depression, anxiety and hopelessness scores.

Conclusions: It can be concluded that the breast cancer patients with extraversion personality traits have lower levels of anxiety and depression, keeping their quality of life better, whereas the patients with higher neuroticism scores may have more impaired quality of life. Therefore, the psychiatric evaluation of the breast cancer patients during and after the treatment cannot be ruled out.
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http://dx.doi.org/10.5152/ejbh.2018.3724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939973PMC
April 2018

Possible role of stress, coping strategies, and life style in the development of breast cancer.

Int J Psychiatry Med 2018 05 2;53(3):207-220. Epub 2018 Jan 2.

11 Department of General Surgery, Faculty of Medicine, 37516 Istanbul University , Istanbul, Turkey.

Objective The aim of the present study was to investigate the possibility of the effect of life long stressful events, along with coping method used, perception of social support, and life style on the development of breast cancer. Methods In this hospital-based case control study, the study group comprised 250 women with breast cancer who were followed by Florence Nightingale Breast Study Group. Control group included 250 women, who had similar sociodemographic characteristics to the study group. Data were collected with semi-structured interview form, Healthy Life Style Behavior Scale, Coping Strategy Indicator, and Stress Evaluation Form developed by us. Results In multivariate analysis, family history of cancer (OR: 1.55, 95% CI: 2.29-1.05), inadequate social support (OR: 1.83, 95% CI: 1.23-2.73), and loss of father during childhood (OR: 2.68, 95% CI: 5.52-1.30) and serious stressor within the last five years (OR: 4.72, 95% CI: 7.03-3.18) were found to be risk factors increasing the risk of breast cancer. When family history of cancer was excluded from the model, the presence of psychiatric disorder history (OR: 1.95, 95% CI: 3.26-1.17) and major life events (OR: 2.24, 95% CI: 4.07-1.24) were added to the model as risk factors. Conclusion The present study indicates that especially the stressful events experienced within the last five years plays an undeniable role in the risk of breast cancer. Social support may be as important in the period before the diagnosis as in the period after diagnosis.
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http://dx.doi.org/10.1177/0091217417749789DOI Listing
May 2018

Roles of Biopsychosocial Factors in the Development of Breast Cancer.

Eur J Breast Health 2017 Oct 1;13(4):206-212. Epub 2017 Oct 1.

Department of General Surgery, İstanbul Faculty of Medicine, İstanbul University, İstanbul, Turkey.

Objective: The aim of this study was to determine the roles of biopsychosocial risk factors in the development of breast cancer.

Materials And Methods: This hospital-based case-control study included 491 women with breast cancer (study group) and 512 women who did not have cancer or other serious diseases (control group). Biological, psychological, and social risk factors were compared between the two groups. Data were collected using the semi-structured interview, the Stress Assessment Form, and the Coping Strategy Indicator to assess these factors.

Results: When the significantly different biopsychosocial variables between the study and the control groups were evaluated together, independent breast cancer risk factors were found as follows: a stressor experienced in the last 5 years, age 40 years and older, inadequate social support perception, use of avoidance coping strategy, being a housewife, having a family history of cancer, and having a body mass index ≥25.

Conclusion: This study showed a relationship between breast cancer risk and manageable variables (obesity, stressor and coping strategy, social support, and employment status), age and family history of cancer, which are biopsychosocial factors. Biopsychosocial aspects are becoming a greater part of many different healthcare systems.
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http://dx.doi.org/10.5152/ejbh.2017.3519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648278PMC
October 2017

Preoperative Lymphedema-Related Risk Factors in Early-Stage Breast Cancer.

Lymphat Res Biol 2018 02 27;16(1):28-35. Epub 2017 Mar 27.

9 Department of Breast Surgery, Istanbul University Istanbul Medical Faculty , Istanbul, Turkey .

Background: Prolongation of survival in patients with breast cancer due to early diagnosis and modern methods of treatment has turned the attention on lymphedema, which is the most important morbidity secondary to the treatment of the disease. Determination of lymphedema and related risk factors in patients before a surgical intervention may provide protection for patients and early treatment. The aim of this study was to determine the presence of lymphedema before surgery by bioimpedance analysis in patients with breast cancer and to establish risk factors associated with lymphedema.

Patients And Methods: A total of 277 patients who were diagnosed as having breast cancer, were planned to undergo a surgical intervention, and had no clinical lymphedema were included in the study. The presence of lymphedema was evaluated with clinical examination, measurement of arm circumference, and bioimpedance analysis.

Results: Lymphedema was found in 59 (21.3%) patients with no detected differences in arm circumferences. A significant relationship was found between the presence of lymphedema and body mass index (BMI), number of positive lymph nodes, and capsule invasion of the tumor (p = 0.001, p = 0.003, p = 0.002, respectively). Multiple regression analysis revealed that BMI and the number of positive lymph nodes were independent variables (p = 0.024, p = 0.002). ROC curve analysis resulted in an increased risk of preoperative lymphedema when the number of positive lymph nodes was ≥8. Correlation analysis revealed a positive correlation between the number of positive lymph nodes and L-dex score (p = 0.001, r = 0.219).

Conclusion: Preoperative bioimpedance analysis demonstrated that ∼1/5 of the patients had subclinical lymphedema. Preoperative subclinical lymphedema is associated with obesity and the number of positive lymph nodes, and thus, treatment of the axilla in patients who are preoperatively detected to have subclinical lymphedema should be revised.
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http://dx.doi.org/10.1089/lrb.2016.0045DOI Listing
February 2018

Receptor discordance rate and its effects on survival in primary and recurrent breast cancer patients.

J BUON 2016 Nov-Dec;21(6):1425-1432

Gaziosmanpasa Taksim Training & Research Hospital, Dept of General Surgery, Istanbul, Turkey.

Purpose: The receptor status of breast cancer plays a critical role in clinical practice. During the metastatic process, a change in the biological characteristics of the tumor can be seen. This study aimed to investigate the hormone receptor and HER2 status changes between primary and recurrent breast cancers and their effect on survival.

Methods: Eighty-six breast cancer patients with biopsy- proven local recurrences or distant metastases during the follow-up period were included in the study. Patients with metastatic disease at the time of first diagnosis or with history of previous neoadjuvant chemotherapy were excluded.

Results: Forty-three of the 86 patients (50%) had changes in at least one of the estrogen receptor (ER), progesterone receptor (PR), or HER2. ER, PR and HER2 discordance rates were 12.7, 38.3, and 15.1%, respectively, and PR discordance was significantly higher (p=0.000). Among all molecular subtypes, the triple negative breast cancer (TNBC) subtype showed the least change. When the effect of chemotherapy on receptor change was analyzed, PR discordance was significantly higher in the group who received chemotherapy (p=0.029). Analysis of the hormonotherapy effects on receptor discordance revealed results similar to those of chemotherapy. Only the PR discordance was significantly greater in the group that received hormonotherapy (p=0.000). None of the three receptor discordances or loss of any receptor were related to survival. Primary tumor TNBC subtype and disease-free-interval (DFI) shorter than 5 years were found as independent prognostic factors that negatively affected overall survival (OS).

Conclusion: This study showed that during recurrent disease there was 50% discordance in the expression of ER, PR, and HER2. The receptor showing the greatest discordance and influence from the systemic treatment was PR. A significant relationship between receptor discordance and survival could not be demonstrated in our study.
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June 2017

The Role of Genomic Profiling in Advanced Breast Cancer: The Two Faces of Janus.

Authors:
Yesim Eralp

Transl Oncogenomics 2016 14;8(Suppl 1):1-7. Epub 2016 Aug 14.

Professor of Medical Oncology, Istanbul University Institute of Oncology, Topkapi, Fatih, Istanbul, Turkey.

Recent advances in genomic technology have led to considerable improvement in our understanding of the molecular basis that underpins breast cancer biology. Through the use of comprehensive whole genome genomic profiling by next-generation sequencing, an unprecedented bulk of data on driver mutations, key genomic rearrangements, and mechanisms on tumor evolution has been generated. These developments have marked the beginning of a new era in oncology called "personalized or precision medicine." Elucidation of biologic mechanisms that underpin carcinogenetic potential and metastatic behavior has led to an inevitable explosion in the development of effective targeted agents, many of which have gained approval over the past decade. Despite energetic efforts and the enormous support gained within the oncology community, there are many obstacles in the clinical implementation of precision medicine. Other than the well-known biologic markers, such as ER and Her-2/neu, no proven predictive marker exists to determine the responsiveness to a certain biologic agent. One of the major issues in this regard is teasing driver mutations among the background noise within the bulk of coexisting passenger mutations. Improving bioinformatics tools through electronic models, enhanced by improved insight into pathway dependency may be the step forward to overcome this problem. Next, is the puzzle on spatial and temporal tumoral heterogeneity, which remains to be solved by ultra-deep sequencing and optimizing liquid biopsy techniques. Finally, there are multiple logistical and financial issues that have to be meticulously tackled in order to optimize the use of "precision medicine" in the real-life setting.
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http://dx.doi.org/10.4137/TOG.S39410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986714PMC
August 2016

Concomitant etoposide and cisplatin provided improved survival compared with docetaxel and cisplatin in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy.

Medicine (Baltimore) 2016 Jul;95(30):e4280

Department of Medical Oncology, Institute of Oncology Department of Radiation Oncology Department of Thoracic Surgery Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Presently, there is no consensus regarding which chemotherapy regimen is best to administer with radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Herein, our aim was to compare the outcome of patients treated with either etoposide-cisplatin (EP) or docetaxel-cisplatin (DP) in this curative setting.Patients treated with either EP or DP and concurrent radiotherapy from 2004 to2012 were identified and their detailed medical records and follow-up information were obtained for analysis in this retrospective study. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding parameters provided by propensity score methods.A total of 105 patients were treated with concurrent chemoradiotherapy for LA-NSCLC (stage IIB-IIIA-IIIB). The median ages were 54 years (range, 32-70 years) and 55 years (range, 37-73 years) in the EP (n = 50) and DP (n = 55) groups, respectively. The median follow-up time was 27 months (range, 1-132 months) in the EP group and 19 months (range, 1-96 months) in DP group. There was no significant difference in baseline clinicopathologic features including age, sex, performance status, histologic subtype, and clinical TNM stages between groups. In the univariate analysis, the median overall survival of patients treated with EP was higher than that of patients treated with DP (41 vs. 20 months, P = 0.003). Multivariate analysis further revealed a survival advantage with EP compared with DP (hazard ratio [HR], 0.46; 95% confidence interval: 0.25-0.83; P = 0.009). The toxicity profile of the 2treatment groups was similar except that pulmonary toxicity was higher in the DP group (grade 3-4: 0% vs. 6%, P = 0.024).Concurrent chemoradiotherapy with EP may provide more favorable outcomes than DP and with an acceptable safety profile.
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http://dx.doi.org/10.1097/MD.0000000000004280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5265838PMC
July 2016

The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer.

Cureus 2016 Jun 7;8(6):e633. Epub 2016 Jun 7.

Department of Surgery, Istanbul University.

Background: Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women.

Methods: Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS).

Results: Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24-252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35-40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015).

Conclusion: Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35-40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival.
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http://dx.doi.org/10.7759/cureus.633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938212PMC
June 2016

True Local Recurrences after Breast Conserving Surgery have Poor Prognosis in Patients with Early Breast Cancer.

Cureus 2016 Mar 24;8(3):e541. Epub 2016 Mar 24.

Department of Surgery, Istanbul University.

Background: This study was aimed at investigating clinical and histopathologic features of ipsilateral breast tumor recurrences (IBTR) and their effects on survival after breast conservation therapy.

Methods: 1,400 patients who were treated between 1998 and 2007 and had breast-conserving surgery (BCS) for early breast cancer (cT1-2/N0-1/M0) were evaluated. Demographic and pathologic parameters, radiologic data, treatment, and follow-up related features of the patients were recorded.

Results: 53 patients (3.8%) had IBTR after BCS within a median follow-up of 70 months. The mean age was 45.7 years (range, 27-87 years), and 22 patients (41.5%) were younger than 40 years. 33 patients (62.3%) had true recurrence (TR) and 20 were classified as new primary (NP). The median time to recurrence was shorter in TR group than in NP group (37.0 (6-216) and 47.5 (11-192) months respectively; p = 0.338). Progesterone receptor positivity was significantly higher in the NP group (p = 0.005). The overall 5-year survival rate in the NP group (95.0%) was significantly higher than that of the TR group (74.7%, p < 0.033). Multivariate analysis showed that younger age (<40 years), large tumor size (>20 mm), high grade tumor and triple-negative molecular phenotype along with developing TR negatively affected overall survival (hazard ratios were 4.2 (CI 0.98-22.76), 4.6 (CI 1.07-13.03), 4.0 (CI 0.68-46.10), 6.5 (CI 0.03-0.68), and 6.5 (CI 0.02- 0.80) respectively, p < 0.05).

Conclusions: Most of the local recurrences after BCS in our study were true recurrences, which resulted in a poorer outcome as compared to new primary tumors. Moreover, younger age (<40), large tumor size (>2 cm), high grade, triple negative phenotype, and having true recurrence were identified as independent prognostic factors with a negative impact on overall survival in this dataset of patients with recurrent breast cancer. In conjunction with a more intensive follow-up program, the role of adjuvant therapy strategies should be explored further in young patients with large and high-risk tumors to reduce the risk of TR.
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http://dx.doi.org/10.7759/cureus.541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846390PMC
March 2016

The Relationship between Bone Mineral Density and Estrogen Receptor Positivity in Patients with Breast Cancer.

J Breast Health 2016 Jul 1;12(3):119-122. Epub 2016 Jul 1.

Florence Nightingale Breast Study Group, İstanbul, Turkey.

Objective: The effect of estrogen on bone mineral density (BMD) and breast cancer has been known for a long time. The aim of this study was to compare of the BMD of patients with breast cancer and healthy individuals, and to investigate the degree of correlation of estrogen receptor (ER) with BMD.

Materials And Methods: Seventy-one patients with postmenopausal breast cancer and 79 healthy dividuals were included in the study. The patient demographics (age, menopause age, body mass index, number of children, BMD, Z scores, and estrogen status for breast cancer patients) were taken from hospital records.

Results: No significant difference was detected between the case and control groups in lumbar region Z scores (p=0.074). At the femur neck, the control group Z scores was higher than patient group (p=0.002). BMI was higher in the patients with breast cancer (p=0.001). There was no statistically significant correlation between ER positivity, BMD, and BMI in ER-positive patients (p=0.495, p=0.8, p=0.846, respectively). There was no difference between the Z scores when the patients were divided into two groups as ER positive and negative (p=0.156, p=0.335, respectively).

Conclusion: This study revealed that there is no difference in lumbar region Z scores between patients with breast cancer and heathy controls; however, the Z scores were higher in the femur neck in the control group, and the BMI was lower in the patient group. Tumor ER positivity does not positively affect BMD.
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http://dx.doi.org/10.5152/tjbh.2016.2961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351481PMC
July 2016

Metaplastic Breast Carcinoma Versus Triple-Negative Breast Cancer: Survival and Response to Treatment.

Medicine (Baltimore) 2015 Dec;94(52):e2341

From the Department of Medical Oncology (AA, FS, RC, YE, PS); Department of Radiation Oncology (MT, MF, SK); Surgical Oncology Unit, Institute of Oncology (HK); Department of Pathology (SO, EY); and Surgical Oncology Unit, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey (MM, AI).

Metaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ± 9% vs. 82 ± 6%, P = 0.013) and overall survival (OS) (68 ± 8% vs. 94 ± 4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required.
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http://dx.doi.org/10.1097/MD.0000000000002341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291613PMC
December 2015

Is administration of trastuzumab an independent risk factor for developing osteonecrosis of the jaw among metastatic breast cancer patients under zoledronic acid treatment?

Medicine (Baltimore) 2015 May;94(18):e671

From the Department of Oncology (KNP, CO, CT), Bilim University, Avrupa Florence Nightingale Hospital, Sishane, Istanbul; Department of Radiation Oncology (GA), Gayrettepe Florence Nightingale Hospital, Besiktas; Department of Surgery (DS, SI, VO), Istanbul Florence Nightingale Hospital, Sisli, Istanbul; Department of Radiology (FC), Gayrettepe Florence Nightingale Hospital, Besiktas; Department of Physical Therapy and Rehabilitation (ZE), Bilim University, Florence Nightingale Hospital; Department of Radiology (FA), Istanbul Florence Nightingale Hospital, Sisli; Department of Oncology (GD), Acıbadem Hospital, Maslak Sarıyer; and Department of Oncology (YE), Istanbul Medical Faculty, Capa, Fatih, Istanbul, Turkey.

One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect.Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients' ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13-82) and the mean number of ZA infusions was 38 (range: 15-56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab.
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http://dx.doi.org/10.1097/MD.0000000000000671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602532PMC
May 2015

Abundant circulating microRNAs in breast cancer patients fluctuate considerably during neoadjuvant chemotherapy.

Oncol Lett 2014 Aug 28;8(2):845-848. Epub 2014 May 28.

Department of Clinical Oncology, Oncology Institute, Istanbul University, Istanbul 34093, Turkey.

Previous studies have revealed the aberrant expression of a number of microRNAs (miRNA/miRs) in the blood circulation of patients with breast cancer (BC). The aim of the present study was to assess the effect of neoadjuvant chemotherapy on the levels of a panel of BC-associated miRNAs, which are at relatively low (let-7, miR-10b, miR-34, miR-155, miR-200c and miR-205) or abundant (miR-21, miR-195 and miR-221) levels in the circulation. Patients with primary operable or locally advanced BC were enrolled in the study. The plasma levels of the miRNAs at baseline and at the fourth cycle of treatment were compared. Patients with stage II disease exhibited higher basal miRNAs levels than those with higher stages. The difference was most evident for miR-155 and miR-21 (P=0.05). From the initial to the fourth cycle of chemotherapy, the miRNA levels changed substantially. In samples in which the miRNA levels generally declined, a marked decrease (≤15,500-fold) was evident for the abundant miRNAs. Notably, the occurrence of a decrease in miRNA levels was more frequent in patients with smaller tumor sizes (P<0.05 for miR-21 and miR-195). This proof-of-concept study provides evidence that highly expressed miRNAs are affected most frequently by chemotherapy, particularly in patients with early stage tumors. This information may be valuable in assessing the response of the patients to therapy.
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http://dx.doi.org/10.3892/ol.2014.2188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081437PMC
August 2014

The Outcome of Patients with Triple Negative Breast Cancer: The Turkish Oncology Group Experience.

J Breast Health 2014 Oct 1;10(4):209-215. Epub 2014 Oct 1.

Department of Radiation Oncology, Ege University Faculty of Medicine, İzmir, Turkey.

Objective: 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: 164; 51.9%). Majority of the patients (87.7%) received adjuvant chemotherapy. 5 year overall survival (OS) and disease-free survival (DFS) rates were 84.6% and 71.6%, respectively. Univariate analysis revealed locally advanced disease (p: 0.001), advanced pathological stage (p: 0.021), larger tumor size (T1&T2 vs T3&T4) (p<0.001), nodal positivity (p: 0.006), and extensive nodal involvement (p<0.001) as significant factors for DFS; whereas, advanced pathological stage (p: 0.017), extensive nodal involvement (p<0.001) and larger tumor size (p: 0,001) and presence of breast cancer-affected member in the family (p=0.05) were identified as prognostic factors with an impact on OS. Multivariate analysis revealed larger tumor size (T3&T4 vs T1&T2) and presence of lymph node metastases (node-positive vs node-negative) as significant independent prognostic factors for DFS (Hazard ratio (HR): 3.03, 95% CI: 1.71-5.35, p<0.001 and HR: 1.77, 95% CI: 1.05-3.0, p=0.03, respectively). Higher tumor stage was the only independent factor affecting overall survival (HR: 2.81; 95% CI, 1.27-6.22, p=0.01).

Conclusion: The outcome of patients with TNBC in this cohort is comparable to other studies including TNBC patients. Tumor size and presence of lymph node metastasis are the major independent factors that have effect on DFS, however higher tumor stage was the only negative prognostic factor for OS.
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http://dx.doi.org/10.5152/tjbh.2014.1904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351517PMC
October 2014

Nine weeks versus 1 year adjuvant trastuzumab in patients with early breast cancer: an observational study by the Turkish Oncology Group (TOG).

Breast Cancer 2015 Sep 12;22(5):480-5. Epub 2013 Dec 12.

Ankara Üniversitesi Tıp Fakültesi; Tıbbi Onkoloji BD, Dikimevi, Ankara, 06590, Turkey,

Background: Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey.

Methods: Records of 680 patients with HER2-positive early breast cancer who received adjuvant trastuzumab plus chemotherapy were obtained and patients were followed up to compare the disease-free survival (DFS) outcome of 9 weeks versus 1 year trastuzumab.

Results: Nine weeks and 1 year trastuzumab was given to 202 (29.7 %) and 478 (70.3 %) patients, respectively. There was a significantly lower rate of patients with negative lymph nodes in the 9-week trastuzumab group. At median 3 years of follow-up from the date of starting trastuzumab, the DFS rates were 88.6 and 85.6 %, respectively (p = 0.670). When adjusted for all the prognostic factors that were significant on univariate analysis, again there was no significant difference in DFS between the groups (HR 0.675; 95 % CI 0.370-1.231; p = 0.200). Cardiac toxicity defined as a ≥15 % decrease in LVEF was significantly higher in the 1-year trastuzumab group (1.88 % versus none for 1-year and 9-week trastuzumab groups, respectively; p = 0.050).

Conclusion: The results of this observational study suggest that DFS outcome of 9 weeks of adjuvant trastuzumab may be comparable to 1 year adjuvant trastuzumab: this needs confirmation by randomized trials.
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http://dx.doi.org/10.1007/s12282-013-0506-yDOI Listing
September 2015

A high serum level of M65 is associated with tumour aggressiveness and an unfavourable prognosis for epithelial ovarian cancer.

Cancer Chemother Pharmacol 2013 Aug 26;72(2):437-44. Epub 2013 Jun 26.

Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Purpose: This study was conducted to determine the clinical significance of serum M30 and M65 in epithelial ovarian cancer (EOC).

Methods: A total of 56 patients with EOC and 56 healthy women were included in the study. All of the patients received platinum-based chemotherapy. Pretreatment levels of M30 and M65 were measured using the quantitative ELISA method.

Results: The median M30 and M65 serum levels were significantly elevated in the EOC patients compared with the healthy controls (96.7 vs. 69.5, p = 0.028 and 436.4 versus 166.3, p < 0.001, respectively). The cut-off value of 423.4 U/L for M65 determined with ROC analysis, predicted progression with 75.1 % sensitivity and 65.6 % specificity (AUC = 0.708, p = 0.008). Patients with higher M65 levels had shorter progression-free survival (PFS) (p = 0.021). Both M30 and M65 serum levels were significantly higher for serous-type histology (p = 0.001 and p < 0.001, respectively). Increased M65 serum levels were associated with advanced disease (p = 0.005) and higher grade (p = 0.005). Moreover, M65 levels were higher for chemotherapy-resistant patients (p = 0.04). Multivariate analysis revealed that an elevated serum M65 level was the only significant independent prognostic factor (p = 0.039, HR 3.792).

Conclusions: These results indicated that serum M30 and M65 levels were significantly elevated in patients with EOC compared with healthy women. Particularly, high serum M65 levels were associated with poor prognosis and resistance to platinum-based chemotherapy.
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http://dx.doi.org/10.1007/s00280-013-2212-zDOI Listing
August 2013

Phase II study of loading-dose ibandronate treatment in patients with breast cancer and bone metastases suffering from moderate to severe pain.

Onkologie 2012 24;35(5):254-8. Epub 2012 Apr 24.

Medical Oncology Department, Hacettepe University School of Medicine, Sıhhiye, Ankara, Turkey.

Background: The aim of this study was to determine the efficacy and safety of loading-dose intravenous (i.v.) ibandronate in women with breast cancer and bone metastases.

Patients And Methods: In this prospective, phase II, open-label study, 13 women with breast cancer, bone metastases, and moderate/severe bone pain received ibandronate 6 mg/day (i.v. loading-dose 15 min infusion over 3 consecutive days) with follow-up until day 14. Endpoints included pain response (primary), duration until pain response, analgesic use, Karnofsky index, safety (including hematologic, biochemical, and urine examinations), and adverse events.

Results: Pain intensity decreased on days 7 and 14 versus day 1 (mean visual analogue scale score: 3.2 ± 2.2 and 3.0 ± 2.1 versus 6.1 ± 0.9, respectively; p < 0.01 for both). Mean time to pain response was 8.2 ± 3.3 days. Mean rate of analgesic use decreased (69.2%, 16.7% and 15.4% on days 1, 7 and 14, respectively). Mean Karnofsky index score increased (80.8 ± 13.1 and 80.8 ± 13.2, on days 7 and 14 versus 77.7 ± 11.7 on day 1; p < 0.05 on both days).

Conclusion: Bone pain and analgesic use decreased in women with breast cancer and bone metastases following loading dose i.v. ibandronate which was well-tolerated with no renal safety concerns.
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http://dx.doi.org/10.1159/000338369DOI Listing
January 2013

Predictive role of midtreatment changes in survivin, GSTP1, and topoisomerase 2α expressions for pathologic complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Am J Clin Oncol 2013 Jun;36(3):215-23

Department of Medical Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey.

Introduction: The primary aim of this study is to investigate the effect of change in the expression levels of survivin, glutathione-S-transferase P1 (GSTP1), and topoisomerase 2α (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy.

Methods: This study included 32 locally advanced breast cancer patients. Tumoral expressions of survivin, TOP2A, and GSTP1 in serial biopsy specimens obtained before treatment, after sequential 4 cycles of doxorubicin+cyclophosphomide, and 4 cycles of docetaxel were analyzed by real-time polymerase chain reaction. Survivin expressions were additionally analyzed in serial blood samples.

Results: The pathologic complete response (pCR) rate and the overall response rate (clinical complete and partial) were 28% (n=9) and 91% (n=29), respectively. There were no statistically significant correlations between serial TOP2A expression levels and response. There was a nonsignificant trend toward an improved response rate with decreased survivin expression. A significant decrease in the GSTP1 expression level throughout treatment (P=0.014), which was also shown to be significantly correlated with a pCR (P=0.0001), was seen. Downregulation of GSTP1 after 4 cycles of anthracycline-based combination was independently associated with improved progression-free survival (P=0.01).

Conclusions: Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.
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http://dx.doi.org/10.1097/COC.0b013e318243913fDOI Listing
June 2013

Association of clinical and pathological variables with survival in thymoma.

Med Oncol 2012 Sep 6;29(3):2221-8. Epub 2011 Nov 6.

Department of Medical Oncology, Institute of Oncology, Istanbul University, Capa, Istanbul 34093, Turkey.

Our aim was to evaluate clinical and pathological features in prognosis of thymoma patients with particular emphasis on patients with myasthenia gravis (MG). From 1995 to 2010, 140 thymoma patients (women/men: 63/77) with a median age of 46 years (11-80 years) were admitted to our institution. According to World Health Organization (WHO), there were 23 (17%) type A, 12 (9%) type AB, 24 (17%) type B1, 42 (31%) type B2 and 36 (26%) type B3. The distribution of Masaoka stages I, II, III and IV was 24 (17%), 71 (51%), 18 (13%) and 27 (19%), respectively. MG coexisted in 61% of patients. After a mean follow-up of 34 months (1-158 months), 102 (73%) patients are alive and well while 14 (10%) are alive with disease. Twenty-three patients (16%) have died, only 9 died of thymoma. In univariate analyses, completeness of resection (P < .001), WHO histology (P = .008), Masaoka stage (P < .001) and MG (P = .002) were significant prognostic factors for progression-free survival (PFS). Young age (P = .008); Masaoka stages 1 and 2 (P = .039); WHO types A, AB and B1 (P = .031); complete resection (P = .024) and presence of MG (P = .05) significantly correlated with overall survival (OS). In multivariate analysis, Masaoka stages 1 and 2 (P = .038) and presence of MG (P = .01) were significantly correlated with a longer PFS; MG (P = .021) and WHO subtype (P = .022) were found to be significant prognostic factors for OS. Adjuvant radiotherapy improved neither OS nor PFS in completely resected stage 2 thymoma. Masaoka staging, WHO and MG are major determinants of prognosis in Turkish thymoma patients. Additionally, radiotherapy did not provide survival advantage to stage 2 patients with complete resection.
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http://dx.doi.org/10.1007/s12032-011-0101-zDOI Listing
September 2012

Clinical and pathological features of breast cancer associated with the pathological complete response to anthracycline-based neoadjuvant chemotherapy.

Oncology 2011 9;81(1):30-8. Epub 2011 Sep 9.

Department of Medical Oncology, University of Istanbul, Istanbul, Turkey.

Objective: Patients with breast cancer with a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a better prognosis than patients with residual disease. The aim of the current study was to identify predictors of pCR.

Methods: This retrospective study included 388 patients treated with anthracycline-based NAC. Clinicopathological parameters were compared between the patients with and without pCR in breast and axilla.

Results: Treatment consisted of FAC/FEC in 230 patients (59%), TAC in 39 (10%) patients and AC followed by docetaxel in 119 (31%). In all, 36 (9.3%) patients had pCR. In univariate analysis, age, tumor size, lymph node involvement, tumor grade (p = 0.077, n = 265), ER and HER-2 status (n = 213), lymphovascular invasion (LVI), type of chemotherapy and taxane-containing chemotherapy were associated with pCR. In multivariate analysis, ER negativity (p = 0.003), the absence of LVI (p = 0.009) and taxane-containing NAC (p = 0.026) were found to be significant indicators of pCR. Median follow-up time was 69 months. Progression-free survival was significantly improved in patients achieving pCR (p = 0.001).

Conclusions: pCR is associated with a better outcome regardless of clinical and pathological parameters in breast cancer patients who receive NAC. The probability of pCR was higher in ER-negative, LVI-negative tumors and in patients treated with sequential taxane-containing chemotherapy.
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http://dx.doi.org/10.1159/000330766DOI Listing
December 2011

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study.

Clin Lung Cancer 2011 Sep 8;12(5):286-92. Epub 2011 May 8.

Institute of Oncology, Istanbul University, Turkey.

Background: The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non-small-cell lung cancer (NSCLC) patients.

Materials And Methods: Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m(2)) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m(2)) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated.

Results: Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months.

Conclusion: Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.
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http://dx.doi.org/10.1016/j.cllc.2011.03.030DOI Listing
September 2011

Factors related to recurrence after pathological complete response to postoperative chemotherapy in patients with epithelial ovarian cancer.

Tumori 2009 Mar-Apr;95(2):207-11

Department of Medical Oncology, Faculty of Medicine, Trakya University, Edirne, Turkey.

Aims And Background: It has been appreciated for some time that the lack of detection of ovarian cancer at clinical and pathological (second-look laparotomy) evaluation is not synonymous with cure. The goal of this study was to define clinical risk factors for recurrence after complete pathological response to postoperative chemotherapy in patients with epithelial ovarian cancer.

Methods: Fifty-seven patients who met the inclusion criteria of our study were evaluated. The characteristics (age, menopausal status, histological subtype, tumor grade, presence of ascites at diagnosis, type of omentectomy, FIGO stage, and residual tumor volume after primary surgery) of patients with and those without tumor recurrence were compared.

Results: The median follow-up was 52 months (range, 15-142 months). The overall survival rates of the patients were 100%, 96%, and 87% at 1, 3 and 5 years, respectively. At the time of the study analysis, 21 of 57 (37%) patients had recurrent disease. The median time to recurrence was 16 months. Recurrences were most frequent in the pelvis and abdominal cavity (38%). Age, menopausal status, stage at diagnosis, and residual tumor volume after initial surgery were significantly related to the risk of recurrence in univariate analysis (P = 0.039, 0.038, 0.004, and 0.000, respectively). Residual tumor volume after initial surgery was found to be the only significant independent prognostic factor (P = 0.049, HR: 0.16, 95% CI: 0.02-0.99).

Conclusion: We believe it is necessary to conduct randomized studies on this issue because insight into predictors of recurrence after pathological complete response to postoperative chemotherapy could be used to select patients for trials of consolidation therapy.
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July 2009

Yolk sac tumours of the ovary: evaluation of clinicopathological features and prognostic factors.

Eur J Obstet Gynecol Reprod Biol 2009 Oct 5;146(2):210-4. Epub 2009 May 5.

Department of Medical Oncology, Faculty of Medicine, Trakya University, Turkey.

Objective: To evaluate the clinicopathological prognostic features, factors and outcomes of chemotherapy in ovarian yolk sac tumours (YST).

Study Design: We reviewed the medical records of 32 women with ovarian YST treated from 1990 to 2006 at two centres.

Results: The median follow-up was 36 months. The median age was 22 (range, 9-68). Two patients were postmenopausal. The most common symptoms at diagnosis included abdominal swelling or mass (72%) and abdominopelvic pain (62%). The location of the tumour was bilateral in 2 cases. Eight patients were in stage I, 4 patients in stage II, 17 patients in stage III, and 3 patients in stage IV. Eighteen patients underwent unilateral salpingo-oophorectomy, two bilateral salpingo-oophorectomy and two cystectomy, while 10 patients had total abdominal hysterectomy and two bilateral salpingo-oophorectomy. Of 32 patients who received postoperative chemotherapy, 27 were treated with a bleomycin/etoposide/cisplatin (BEP) regimen. Seventy-two percent of patients were alive at the last follow-up visit. Ten (31%) patients suffered from a recurrence of the disease with a median time to recurrence of 8 months (range, 6-28 months). The most common site of recurrence was the intra-abdominal space, with 8 patients. Only one patient who had recurrence could be salvaged. Fertility-sparing surgery was found at least as effective as radical surgery. While age, histology (mixed vs. pure), stage, tumour size, ascites, and marker levels were not found as prognostic factors, the presence of residual tumour (P=0.014) and BEP chemotherapy (P=0.016) were significant prognostic factors in univariate analysis.

Conclusions: In patients with ovarian YST, fertility-sparing surgery is as effective as radical surgery. Optimal cytoreductive surgery and standard BEP regimen are the most decisive prognostic factors. In these tumours, adjunctive therapeutic modalities to eradicate intra-abdominal disease and effective salvage therapy strategies are needed.
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http://dx.doi.org/10.1016/j.ejogrb.2009.02.052DOI Listing
October 2009

Malignant ovarian germ cell tumors: a single-institution experience.

Am J Clin Oncol 2009 Apr;32(2):191-6

Department of Medical Oncology, Faculty of Medicine, Trakya University, Edirne; Turkey.

Objective: To evaluate the clinicopathologic prognostic factors in malignant ovarian germ cell tumors.

Methods: We reviewed the medical records of 70 patients treated from 1990 to 2006 at our center. Clinical data including demographics, stage, surgery, chemotherapy, survival, menses status, and fertility were collected from patients' charts.

Results: Median age was 22 years (range, 9-68). The histologic subtypes included 36 dysgerminomas, 11 yolk sac tumors, 3 immature teratomas, 1 embryonal carcinomas, and 19 mixed types. The most striking clinicopathologic finding was a history of concomitant immunosuppressant therapy, which was observed in 2 patients. Two patients had contralateral sex-cord tumors at presentation and follow-up. During a median follow-up period of 4.6 years, 11 patients had recurrence. The median time to recurrence was 8 months (6-28 months). Recurrences appeared in the abdominopelvic cavity in 9 out of 11 patients. Only one could be salvaged with second-line chemotherapy. Cumulative survival rate was 97% and 60% in patients with dysgerminoma and nondysgerminoma, respectively. Nondysgerminoma histology and residual tumor after surgery were unfavorable prognostic factors (P < 0.001 and P = 0.015). Fertility-sparing surgery was as effective as radical surgery among all eligible patients. Of patients with known menstrual status, 96% had regular menses. Of the 8 patients who opted for conception among these patients, 7 delivered healthy infants.

Conclusions: Nondysgerminomas have an aggressive clinical course. New treatment strategies are needed for eradication of abdominopelvic disease at initial diagnosis and recurrent setting. Occurrence of malignant ovarian germ cell tumors may be associated with immunosuppression in some patients. Sex-cord stromal tumors may present with bilateral involvement. It is possible to maintain fertility after fertility-sparing surgery followed by chemotherapy.
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http://dx.doi.org/10.1097/COC.0b013e3181841f2eDOI Listing
April 2009
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