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Objective: The aim was to assess the prognostic variables in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients receiving lapatinib plus capecitabine., Materials and Methods: Retrospective data on HER2-positive metastatic breast cancer patients who received lapatinib and capecitabine were analyzed. Survival outcome was obtained with Cox regression analysis and the Kaplan-Meier method., Results: The study included 102 patients. Forty-four (43.1%) patients had de novo metastatic disease. The most frequent metastatic sites were, in order, bone (61.8%), brain (57.8%), liver (35.3%), and lung (34.3%). All of the patients had previously received chemotherapy based on trastuzumab. With combined lapatinib and capecitabine, complete response was observed in 7.8%, partial response in 30.4%, and stable disease in 24.5%. Progression-free survival was 8 (95% confidence interval, 5.1-10.8) months. In multivariable analysis, endocrine therapy ( p = 0.02), de novo metastatic disease ( p = 0.02), and age ( p = 0.02) were prognostic factors for progression-free survival. However, the number of chemotherapy cycles with trastuzumab, palliative radiotherapy, history of breast surgery, and the number of metastatic sites were not significant in this respect., Conclusion: These results have demonstrated the effectiveness of lapatinib plus capecitabine in metastatic HER2-positive breast cancer patients. Furthermore, unfavorable prognostic factors for progression-free survival were shown to be hormone-negative tumor, de novo metastatic disease, and young age., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by the the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (recurrent vs. de novo) and the diagnosis date of MBC (Cohort I: patient diagnosed between January 2010 and December 2014; and Cohort II: between January 2015 and December 2019). Out of 1382 patients analyzed, 52.3% patients had recurrent disease, with an increased frequency over time (47.9% in Cohort I vs. 56.1% in Cohort II, p < 0.001). In recurrent patients, 38.4% ( n = 277) relapsed within two years from initial diagnosis, among which triple-negative BC (TNBC) was the most frequent (51.7%). Median overall survival (OS) was 51.0 (48.0-55.0) months for all patients, which was similar across both cohorts. HER2+ subtype had the highest OS among subgroups (HER2+ vs. HR+ vs. TNBC; 57 vs. 52 vs. 27 months, p < 0.001), and the dnMBC group showed a better outcome than recMBC (53 vs. 47 months, p = 0.013). Despite the lack of CDK inhibitors, luminal A patients receiving endocrine therapy had a favorable outcome (70 months), constituting an appealing approach with limited resources. The only survival improvement during the timeframe was observed in HER2+ dnMBC patients (3-year OS Cohort I: 62% vs. Cohort II: 84.7%, p = 0.009). The incorporation of targeted agents within standard treatment has improved the outcome in HER2+ MBC patients over time. Nevertheless, despite advances in early diagnosis and treatment, the prognosis of patients with TNBC remains poor, highlighting the need for more effective treatment options.

Introduction: Patients with HER2-positive metastatic breast cancer are at risk for developing brain metastases. Different anti-HER2 treatments can be used in the management of the disease. In this study, we aimed to evaluate the prognosis and the factors affecting the prognosis in brain metastatic patients with HER2-positive breast cancer., Methods: Clinical and pathological features of HER2-positive metastatic breast cancer patients and magnetic resonance imaging features at the onset of brain metastasis were recorded. Survival analyses were performed using Kaplan-Meier and Cox regression methods., Results: Analyses of the study were performed by including 83 patients. The median age was 49 (25-76). All patients had HER2 receptor-positive tumors. Thirty-five (42.2%) patients had a hormone-positive disease. Thirty-two (38.6%) patients had de novo metastatic disease. Brain metastasis sites were found to be bilateral - 49.4%, right brain - 21.7%, left brain - 12%, and unknown - 16.9%, respectively. The median brain metastasis largest size was 16 mm (range 5-63). The median follow-up time from the post-metastasis period was 36 months. Median overall survival (OS) was found as 34.9 months (95% CI, 24.6-45.2). In multivariate analysis for factors affecting OS, estrogen receptor status (p = 0.025), number of chemotherapy agents used with trastuzumab (p = 0.010), number of HER2-based therapy (p = 0.010), and the largest size of brain metastasis (p = 0.012) were found to be statistically significant., Conclusions: In this study, we demonstrated the prognosis in brain metastatic patients with HER2-positive breast cancer. When the factors affecting the prognosis were evaluated, we determined that the largest size of brain metastasis, estrogen receptor positivity, and the use of TDM-1 and lapatinib plus capecitabine consecutively during the treatment process affected the prognosis of the disease., (© 2023 S. Karger AG, Basel.)

Objective: Published studies on male breast cancer (MBC) and BRCA mutations are scarce and usually include, a small number of patients. The clinicopathological characteristics of BRCA mutant and wild-type MBC patients were compared in more than forty patients in this study., Materials and Methods: A retrospective review of MBC patients' clinical and histopathological data was conducted. To compare the patients' characteristics, chi-square test and Fisher's Exact test were utilized. Kaplan-Meier analysis was used to examine the survival analysis., Results: In total 43 cases were reviewed. The average duration of follow-up was 35.8 months. BRCA mutations were found in 11 (25.6%) of the patients. BRCA1 mutations were found in four patients (9.3%), BRCA2 mutations in six patients (14%), and BRCA1 and BRCA2 mutations in one patient (2.3%). The median age at diagnosis was 58 years old, and there was no statistically significant difference between groups ( p = 0.7). Tumor location ( p = 0.3), human epidermal growth factor receptor 2 overexpression ( p = 0.5), estrogen receptor status ( p = 0.05), progesterone receptor status ( p = 0.6), tumor stage ( p = 0.9), lymph node positivity ( p = 0.5), tumor histology ( p = 0.06), and recurrence status ( p = 0.6) were similar between BRCA -wild type and -mutated patients. Overall survival averaged 115.6 months (range: 76.0-155.3), with no statistically significant differences between groups ( p = 0.6)., Conclusion: This study investigated clinical and pathological characteristics and prognoses of BRCA wild and mutant-type MBC and these were similar in all groups studied., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by the the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)

Objectives: This study aims to investigate the efficacy of abbreviated breast magnetic resonance imaging (MRI) in neoadjuvant chemotherapy (NAC) response evaluation., Methods: MR images of 50 locally advanced breast cancer patients who underwent standard protocol (SP) breast MRI before and after NAC were re-evaluated retrospectively. Abbreviated protocol (AP) was obtained by extracting images from SP and then evaluating them in a separate session. Protocols were compared with the histological findings after surgery as the reference standard., Results: A statistically significant difference was found between the two protocols in response evaluation by the McNemar test (p=0.018). However, the Kappa value was 0.62 (p<0.001), which indicates substantial agreement. No statistically significant differences were found between the two protocols (AP and SP) and pathological results in the McNemar test (p=0.12, p=0.60, respectively). Kappa values were 0.48 (p<0.001) and 0.60 (p<0.001), respectively, which indicates moderate agreement for both protocols with higher values by SP evaluation. The residual maximum median diameters were smaller than the pathology, with both protocols (p<0.001)., Conclusion: Despite the statistical differences, there was a significant correlation in response evaluation between the two protocols. The pathological results were moderately correlated with both protocols, with SP slightly higher. However, the residual maximum median diameters were smaller than the pathology with both protocols. These results may limit the use of AP in evaluating the local extent of the tumor, especially in patients who will undergo breast-conserving surgery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: The optimal number of neoadjuvant chemotherapy (NACT) cycles is unclear in epithelial ovarian cancer. Our study aimed to evaluate the effect of the number of NACT cycles before interval debulking surgery on survival., Methods: Data of 221 patients with advanced-stage serous epithelial ovarian cancer (EOC) were retrospectively evaluated. The patients were divided into groups as who received 3 cycles of NACT (group A), 4-5 cycles of NACT (group B), and 6 cycles of NACT (group C)., Results: There were 67 (30%) patients in group A, 70 (32%) in group B, and 84 (38%) in group C. Median overall survival (OS) was 61 (range 43-79) months for group A, 44 (range 36-52) months for group B, and 39 (range 27-50) months for group C. In addition, median disease-free survival (DFS) was 23.1 (range 8.5-32.1) months for group A, 19.2 (range 10.1-28.4) months for group B, and 21.5 (range 16-27) months for group C. Patients receiving >3 NACT cycles had worse OS than patients who received 3 NACT cycles (for group A vs. B, p = 0.018; for group A vs. C, p = 0.049). However, in terms of DFS, patients receiving 3 NACT cycles had no statistically significant difference compared to patients who received >3 NACT cycles., Conclusions: Patients with advanced-stage serous EOC who received more than 3 cycles of NACT had poor OS. However, there was no statistical difference in terms of DFS. In addition, >3 cycles of NACT did not increase the probability of achieving complete cytoreduction at the time of surgery., (© 2021 S. Karger AG, Basel.)

Aim: Endometrial cancer is the most common cancer of the female reproductive tract in the developed countries. There are many risk factors defined for the development of endometrial cancer, including obesity. We aimed to evaluate the significance of adiposity on the survival outcomes of the patients with endometrial cancer., Methods: The patients diagnosed with endometrial cancer and underwent surgery between April 2009 and October 2017 were retrospectively reviewed. The visceral adipose tissue and subcutaneous adipose tissue volumes were measured at the level of umbilicus on single-slice magnetic resonance imaging. Visceral adiposity index was calculated. Patients were compared regarding their clinical, demographical, pathologic and survival characteristics. Patients divided into low visceral adiposity (≤0.265, group 1) and high visceral adiposity (>0.265, group 2)., Results: A total of 186 patients were included in this retrospective study. There was no significant difference in terms of the demographical, clinical and tumor characteristics of the patients, except age, menopausal status, subcutaneous adipose tissue and visceral adipose tissue. Although no significant difference in progression-free survival and disease-specific survival was noted between groups (P = 0.181), more patients in group 2 died because of endometrial cancer as statistically significant (P = 0.024). Disease-specific survival showed a significant difference between groups according to the log-rank test., Conclusion: Visceral adiposity tissue is a significant and reliable prognostic indicator for endometrial cancer prognosis. Women diagnosed with endometrial cancer should be informed about the deleterious effects of visceral adiposity on disease-specific survival., (© 2020 Japan Society of Obstetrics and Gynecology.)

Aim: This study investigates the prophylactic effect of henna on the occurrence of hand-foot syndrome (HFS) in patients receiving capecitabine for breast and colorectal cancer., Method: This experimental study was carried out between May 2014 and May 2015. In this self-control experimental study, 52 patients with breast and colorectal cancer were included on the first day of capecitabine treatment and had a minimum follow-up of 3 cycles. One hand/foot of each patient constituted the study hand/foot, whereas the others constituted the control. Henna was administered to the study hand/foot on the first day of treatment and application renewed weekly. Development of grade 1-3 toxicity was set as the termination criterion for study., Results: Painful skin changes such as rawness, intumescence and bulla formation, blocking the daily activities or self-care were observed in 26.9% of the patients in the 3rd or 4th cycles of treatment. Development time and severity of skin changes over time did not differ significantly between the study and the control hand/foot., Conclusion: Further studies with a larger sample size are needed to conclude on the prophylactic effect of henna in the management of the HFS., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (Copyright © 2020 Florence Nightingale Journal of Nursing.)

Background and Aim: Our retrospective, single-center study aimed at evaluating the efficacy and safety of eribulin in heavily pretreated metastatic breast cancer (MBC) in routine clinical practice., Subjects and Methods: Twenty-eight patients treated with eribulin for MBC between May 2014 and November 2017 were included in our study. Clinical and biological assessment of toxicity was controlled at each visit. Tumor response was evaluated every three cycles of treatment., Results: Median age at eribulin treatment was 52.5-year. Tumors were hormone receptor positive (71.4%), HER2-positive (10.7%), and triple negative (TN) (25%). Most of the patients (92.8%) presented with visceral metastases, mainly in the lymph nodes (57.1%) and liver (53.6%). Median previous metastatic chemotherapy line was 4 [1-7]. Median number of metastatic sites were 3 (1-4). Median number of eribulin cycles was 4. At the end of follow-up period, 36% of the patients were still alive. Eighteen patients died due to disease progression. The objective response rate was 21.5% with a 42.9% clinical benefit rate. Median progression-free survival and overall survival (OS) were 4 (95% CI: 2.7-5.2) and 14 (95% CI: 11.8-16.1) months, respectively. Treatment was well tolerated. None of the patients discontinued eribulin treatment due to toxicity. The most commonly reported toxicities were asthenia (71.4%), peripheral neuropathy (67.9%), and neutropenia (46.4%)., Conclusion: Eribulin is an effective new treatment option in heavily pretreated MBC, with a manageable toxicity profile. Our results confirm that treatment with eribulin is feasible and safe in real-world patients., Competing Interests: None

Background: Novel biomarkers are needed to predict the effectiveness of the treatment of presurgical neoadjuvant chemotherapy (NAC) in breast cancer (BC)., Objective: This is an exploratory study to assess the impact of 3 cancer-related long non-coding RNAs (lncRNAs) (H19, MALAT1 and GA5) in blood plasma of patients with BC in predicting the response to NAC., Methods: The plasma levels of RNAs were relatively measured by quantitative PCR at baseline, and at the end of the fourth cycle of NAC in patients with locally advanced BC., Results: Only H19 was associated with patients' characteristics, and with the response to NAC. Higher plasma expression of H19 was associated with younger age at diagnosis, triple negative tumors, and Ki-67 index. Patients with a pathological complete response (20%) had lower pre-therapeutic levels of H19 compared with the non-complete responders (relative levels 0.1 vs 0.2, respectively, P: 0.04). In addition, the patients with higher degree of downstaging of initial tumors had lower baseline levels of H19 among non-complete responders., Conclusion: Our study reveals that H19, but not MALAT1 and GAS5, may be a useful marker of response to NAC in BC.

Objective: Breast cancer is a heterogenous disease, and genetic profiling helps to individualize adjuvant treatment. The Oncotype DX is a validated test to predict benefit of adjuvant systemic treatment. The aims of this study are to determine the costs of chemotherapy in government hospitals in Turkey and evaluate the cost-effectiveness of the Oncotype DX from the national insurance perspective., Materials and Methods: A Markov model was developed to make long term projections of distant recurrence, survival, quality adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative or up to 3 node-positive early stage breast cancer. Turkish decision impact study patient data were captured for model reference. In that study, ten academic centers across Turkey participated in a prospective trial. Of 165 patients with pT1-3, pN0-N1mic, ER-positive, and HER-2 negative tumors, 57% had low recurrence score (RS), 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in chemotherapy treatment decisions following Oncotype DX was 33%., Results: The cost of adjuvant chemotherapy in public hospitals was estimated at $3.649, and Oncotype Dx test was $5.141. Based on the cost-effectiveness analysis, Oncotype DX testing was estimated to improve life expectancy (+0.86 years) and quality-adjusted life expectancy (+0.68 QALYs) versus standard care. The incremental cost-effectiveness ratio (ICERs) of Oncotype DX was estimated to be $7207.9 per QALY gained and $5720.6 per LY gained versus current clinical practice., Conclusion: As Oncotype DX was found both cost-effective and life-saving from a national perspective, the test should be introduced to standard care in patients with ER+, HER-2 negative early-stage breast cancer in Turkey., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare.

Objective: It is known that optimal or complete cytoreduction is the most important factor in patients with advanced ovarian cancer. The aim of this study was to examine the results of patients who did not undergo optimal cytoreduction and to examine subgroup analysis based on neoadjuvant chemotherapy (NAC)., Material and Methods: Patients with advanced ovarian cancer and suboptimal surgery were retrospectively reviewed., Results: A total of 99 patients with a median age of 59.0 years (range, 22-87 years) were studied. The median follow-up time was 39±32.7 months, 81 patients (81.8%) died and 18 patients (18.2%) were alive. The five-year survival rate was 27.6%. Of the patients, 37 (37.4%) were underwent surgery after NAC, 62 (62.3%) were primary. More patients with NAC died within 3 years compared with those without NAC (83.9% vs 56.0%) (p=0.015). Patients with NAC had less tumor spread (presence of visible tumor in the upper abdomen during surgery) (29.7% vs 72.6%; p<0.001) and had less overall survival times when compared with patients who underwent primary surgery [median 22.3±1.2; 95% CI: (19.9-24.7) vs (37.5±11.2); 95% CI: (15.4-59.5) months; log rank test p=0.055]. The relationship between overall survival and factors such as age, NAC, presence of metastasis in the upper abdomen, and tumor histology (serous vs. non-serous) were analyzed using univariate cox regression analysis. Of these factors, only NAC was close to significant, but it did not reach significance (p=0.055)., Conclusion: NAC reduces tumor burden before surgery in advanced ovarian cancer. The prognosis of patients who are not eligible for optimal surgery despite NAC is worse than in patients who do not receive NAC.

Aim: The aim of this study was to determine the clinicopathological characteristics, treatment details and outcome of patients with brain metastasis from epithelial ovarian carcinoma (EOC)., Methods: This study included 21 patients diagnosed with brain metastasis from EOC between 1999 and 2009., Results: Median age was 61 years (range 38-77). The median time elapsed from EOC diagnosis to brain metastasis detection was 32 months. Single brain metastases were found in 10 (48%) cases, and there was extra-cranial disease in 11 (52%) cases. During the mean 86 months of follow-up, 18 of the patients (86%) died of the disease and 3 (14%) were alive with disease. The median survival time after the initial diagnosis of brain metastasis was 9 months. The median overall survival (OS) from initial diagnosis of EOC was 50 months. In univariate analysis, prolonged time from initial diagnosis to central nervous system metastasis (more than 32 months) (p = 0.001), treatment with radiotherapy (p < 0.001), optimal cytoreductive operation (p = 0.02) were all positively correlated with OS., Conclusion: The prognosis of patients with brain metastasis from EOC is still poor. The significant predictors of survival in our series were whole brain radiotherapy, prolonged elapsed time from initial diagnosis to brain metastasis and optimal cytoreductive surgery., (© 2019 S. Karger AG, Basel.)

Immune checkpoint inhibitors have taken an important place in the field of oncologic immunotherapy, especially for patients in whom conventional treatment regimens have failed. Nivolumab prevents programmed cell death 1 (PD-1) and programmed cell death ligand-1 (PD-L1) binding, resulting in blockage of the inhibitory signal and thus facilitating an immunologic antitumor response. Nivolumab has been shown to be effective in thoracic malignancies, including non-small cell lung cancer (NSCLC). Here is a case of 52-year male patient with metastatic lung adenocarcinoma progressing after 4 cycles of chemotherapy. We started nivolumab q2 weeks therapy. Firstly, his dyspnea relieved, carcinoembryonic antigen (CEA) and C-reactive protein (CRP) levels regressed, and then their levels remained constant at a stable level. Radiologically stable response was seen. Progression was seen after about one and half year. Patient died in a short time after progression. In conclusion, this observation provides a strong indication of the potential value of immune checkpoint inhibitors for the management of metastatic lung cancers.

BACKGROUND We compared pathological prognostic stage (PPS) with anatomic stage (AS) groups according to the updated version of breast cancer staging of the American Joint Committee on Cancer (AJCC) 8th Edition. MATERIAL AND METHODS We evaluated 353 breast cancer patients initially treated with surgery. AS and PPS were performed by evaluating the pathological data of the patients according to the AJCC 8th Edition breast cancer updated version. Stages and survival rates between the 2 staging systems were evaluated and compared. Disease-free survival (DFS) and disease-specific survival (DSS) were calculated according to both staging systems using Kaplan-Meier test. After the PPS change was made in each AS group, 10-year DFS and 10-year DSS of the changed groups were compared using the chi-square test. RESULTS The median follow-up was 114 months and the median age was 48 years. In 192 (54.4%) patients the stage change. The most significant change was 1-level downstaging in 70 (22.4%) patients, and 2-levels downstaging in 78 (22.1%) patients. Five-year DFS, 10-year DFS, 5-year DSS rate, and 10-year DSS were 86.3%, 80.3%, 93.8%, and 84.1%, respectively. The PPS system was found to provide better prognostic information when the patients with AS IIB and IIIA groups were compared according to the PPS. CONCLUSIONS According to the updated version of the AJCC 8th Edition, half of our patients had stage change when they were evaluated according to AS and PPS system. PPS gives better information about prognosis than does AS.

Objective: The current rearrangement ratio of BRCA1 and BRCA2 genes is not known in the Turkish population. Rearrangements are not routinely investigated in many Turkish laboratories. This creates problems and contradictions between clinics. Therefore, the aim of this study was to evaluate the distribution and frequency of rearrangements in BRCA1 and BRCA2 genes in high-risk families and to clarify the limits of BRCA1 and BRCA2 testing in Turkey., Materials and Methods: The study included 1809 patients at high risk of breast cancer or ovarian cancer. All patients were investigated for both small indels and rearrangements of BRCA genes using DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis., Results: The overall frequency of rearrangements was 2% (25/1262). The frequency of rearrangements was 1.7% (18/1086) and 4% (9/206) in patients with breast cancer and ovarian cancer, respectively. The frequency of rearrangements was 3.7% (8/215) in patients with triple-negative breast cancer. The rearrangement rate was 7.7% (2/26) in patients with both breast and ovarian cancer., Conclusions: Rearrangements were found with high rates and were strongly associated with bilateral and triple-negative status of patients with breast cancer, which are signs of high risk for breast and ovarian cancer. Analysis of rearrangements should definitely be included in routine clinical practice in Turkey for high-risk families and also for improved cancer risk prediction for families., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Objective: We used the results from the first three screening rounds of Bahcesehir Mammography Screening Project (BMSP), a 10-year (2009-2019) and the first organized population-based screening program implemented in a county of Istanbul, Turkey, to assess the potential cost-effectiveness of a population-based mammography screening program in Turkey., Materials and Methods: Two screening strategies were compared: BMSP (includes three biennial screens for women between 40-69) and Turkish National Breast Cancer Registry Program (TNBCRP) which includes no organized population-based screening. Costs were estimated using direct data from the BMSP project and the reimbursement rates of Turkish Social Security Administration. The life-years saved by BMSP were estimated using the stage distribution observed with BMSP and TNBCRP., Results: A total of 67 women (out of 7234 screened women) were diagnosed with breast cancer in BMSP. The stage distribution for AJCC stages O, I, II, III, IV was 19.4%, 50.8%, 20.9%, 7.5%, 1.5% and 4.9%, 26.6%, 44.9%, 20.8%, 2.8% with BMSP and TNBCRP, respectively. The BMSP program is expected to save 279.46 life years over TNBCRP with an additional cost of $677.171, which implies an incremental cost-effectiveness ratio (ICER) of $2.423 per saved life year. Since the ICER is smaller than the Gross Demostic Product (GDP) per capita in Turkey ($10.515 in 2014), BMSP program is highly cost-effective and remains cost-effective in the sensitivity analysis., Conclusion: Mammography screening may change the stage distribution of breast cancer in Turkey. Furthermore, an organized population-based screening program may be cost-effective in Turkey and in other developing countries. More research is needed to better estimate life-years saved with screening and further validate the findings of our study., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Purpose: Each year, 12.7 million people learn that they have cancer and 8.2 million people die of cancer worldwide. Cancer is a major public health issue which causes fundamental changes in the lives of patients and their families. The purpose of this study was to evaluate the lives of patients after diagnosis and determine the changes in their lifestyles., Methods: Between September 2013 to December 2013, a questionnaire consisting of 22 questions was administered during a face to face interview to patients at 13 different Oncology Units in Turkey. Each patient was queried during the administration of his/her chemotherapy. Eight of the questions featured independent choices, and 14 had dependent (multiple) choices., Results: A total of 1300 patients were included in the study. Of patients 9.5% were 71 years of age and older which was the oldest age group. The mean patient age was 54.6±13.8 years. Of the whole group of patients 58.5% were female and 41.5% male. After diagnosis, 64% of the patients reported that they were complying with guidelines for a healthy lifestyle and 80% said that they were eating healthier food. At the time they filled in the questionnaire, more than half of the patients (57.3%) felt optimistic about their disease., Conclusions: Diagnosis of cancer may change the patients' dietary and reading habits, social relationships, activities and more importantly, their point of life view.

Background and Objectives: It is not clear whether sentinel lymph node biopsy (SLNB) can be applied to patients with a second breast cancer or recurrence occurring at previously treated breast. The purpose of this study was to assess the feasibility of SLNB procedure in patients with recurrent breast cancer., Methods: Patients with non-metastatic recurrent N0 breast cancer at ipsilateral breast were included. Patients were grouped according to their initial breast, axilla, and overall surgery. Presence of drainage and its pattern as well as SLNB success rate and overall axillary involvement rates were assessed. Findings were compared., Results: Out of 75 patients, mean age was 52.5 years and disease-free interval was 82 (9-312) months. Lymphatic drainage was successful in 42 (56%) patients. Drainage positivity was more frequent in patients who were previously treated with SLNB (82.6%) than in patients who underwent axillary lymph node dissection (ALND) (44.2%; P = 0,002). Aberrant lymphatic drainage was detected in 64.3% of drainage positive patients. Success rate of reoperative SLNB was 92.9%. Adjuvant treatment plan was altered in 12 (16%) patients. In 15 patients, negative SLNB prevented axillary dissection., Conclusions: Reoperative SLNB seems to be technically feasible in N0 recurrent breast cancer patients. It may further avoid unnecessary ALND and lead changes in adjuvant treatment plans. J. Surg. Oncol. 2016;114:796-802. © 2016 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the correlations between Recurrence Score (RS) and routine risk factors., Materials and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive patients with breast cancer who had pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at tumor conferences. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classic risk factors were evaluated using univariate and multivariate analyses., Results: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of the 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. Multivariate analysis indicated that progesterone receptor (PR) and Ki67 scores were significantly related to RS., Conclusion: Oncotype DX Recurrence Score does not seem to have a significant correlation with the majority of classic risk factors, but it may have a correlation with PR score and Ki67 score., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Introduction: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX(®) 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the impact of the Recurrence Score(®) (RS) on treatment decisions and physician perceptions in Turkey. We also studied correlations between RS and routine risk factors., Patients and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at multidisciplinary tumor conferences. The initial treatment decision was recorded before tumor blocks were sent to the central laboratory. Each case was brought back to tumor conference after receiving the RS result. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classical risk factors were evaluated using univariate and multivariate analyses., Results: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in treatment decision was 33%. Initially, chemotherapy followed by hormonal therapy (CT+HT) was recommended to 92 (56%) of all patients, which decreased to 61 (37%) patients post-RS assay (p<0.001). Multivariate analysis indicated that progesterone receptor (PR) and Ki-67 scores were significantly related to RS., Conclusion: Oncotype DX testing may provide meaningful additional information in carefully selected patients.

Background: Non-HIV related Kaposi sarcoma (NHKS) is a rare indolent neoplasm which is more common around Mediterranean origin. Data concerning factors that influence progression-free survival (PFS) for NHKS are insufficient. The purpose of present retrospective analysis was to distinguish the factors affecting PFS in patients with NHKS., Methods: A hundred and twenty-eight consecutive patients with NHKS who were treated or observed between 1997 and 2014 at Istanbul University Institute of Oncology were included into the study. Treatment response and progression definitions were determined according to different treatment modalities administered at first line., Results: Majority of patients were male (n = 97, 75.8%). Median age of the whole group was 66 years (28-85). Of the patients, 15 patients were immunosuppressant, whereas 113 patients had no disease that caused immunosuppression. Patients were treated with local excision (n = 57, 44.5%), chemotherapy (n = 32, 25.0%) and/or radiotherapy (n = 13, 10.2%) or observed without treatment (n = 26, 20.3%). At a median follow-up of 28 months, 71 (55.5%) patients had progression, while 3 patients (2.3%) died of NHKS. On univariate analysis, patients who had hypertension (HT) had poorer PFS compared with others (19 ± 12 versus 41 ± 22 months; p = 0.03), whereas plaque formation was associated with better outcome (25 ± 9 versus 54 ± 12 months; p = 0.03). In addition, heavy smoking (≥40 pack-years) had a borderline significance regarding better PFS time (23 ± 24 versus 45 ± 38 months, p = 0.06). On multivariate analysis, none of factors evaluated had any impact on PFS., Conclusions: HT was correlated with poorer outcome among NHKS patients. Patients with plaque formation and ≥40 pack-years of smoking had better PFS than others.

Breast cancer is a complex disease displaying different profiles involving genetic as well as epigenetic factors. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression. Recent studies demonstrated that miRNAs may display great potential for the development of novel biomarkers and therapeutic targets. In the present study, the levels of miR-21 and miR-145 were analyzed in the peripheral blood of 52 patients with luminal A breast cancer. miRNA expression was determined in serum samples from matched pre- and post-treatment patients with breast cancer by quantitative polymerase chain reaction. There were no statistically significant differences in miR-145 and miR-21 levels between pre- and post-treatment samples. In addition, the miRNA levels were not found to be associated with the clinical parameters.

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., Competing Interests: Conflict of Interest: The authors declare no conflict of interest.

Aims: Glutathione S-transferase P1 (GSTP1) plays an important role in cellular protection against oxidative stress and toxic chemicals. Polymorphisms within GSTP1 are associated with alterations in enzyme activity, which may lead to development of lung disease and cancer. In this study, we aimed to investigate the GSTP1 Ile105Val and Ala114Val polymorphisms in patients with small cell lung cancer (SCLC)., Patients/methods: GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala114Val polymorphism in exon 6 were determined by using polymerase chain reaction-restriction fragment length polymorphism techniques in 89 patients with SCLC and 108 control patients with chronic obstructive pulmonary disease (COPD). Genotype frequencies and cigarette smoking intensities were compared among SCLC and COPD patients., Results: There were significantly less SCLC patients with variant exon 6 genotypes than COPD patients (7.9% vs. 20.4%, p=0.007), while the number of patients with variant exon 5 genotypes were comparable among groups. SCLC and COPD patients with variant exon 6 genotype showed trends toward exhibiting reduced cigarette consumption., Conclusions: The variant GSTP1 exon 6 genotype might be conferring protection against SCLC development. Whether this effect is associated with exposure to cigarette smoking needs to be clarified.

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., (Copyright © 2012 S. Karger AG, Basel.)

Purpose: To determine the time elapsed between the first notification of the disease and the access to the diagnosis and treatment modalities and the associated factors in female patients with breast cancer in Turkey., Methods: Data was acquired from a questionnaire involving 535 patients who applied to 14 various oncology clinics in Turkey between 1st and 28th of February 2010. Analyses were performed by the participating clinics and were divided into 3 groups: centers located in metropolitan areas formed group 1 (n=161), those located in Marmara and central Anatolia region formed group 2 (n=189), and centers located in Karadeniz and East-Southeast Anatolia region formed group 3 (n=185). The groups of these centers were formed according to the socioeconomic development of the provinces., Results: The median patient age was 48 years, 56.1% of patients were less than 50 years of age. Eighty-five percent of the patients detected a mass in their breast by self examination and 27% of the patients older than 50 years never had breast imaging until the definite diagnosis was established. The median time elapsed between disease noticed by the patient and application to a health care center was 10 days, between application and biopsy 19 days, between biopsy and surgery 10 days, and between surgery and systemic therapy 31 days. The median time elapsed between patients applying for surgery in groups 1 and 2 centers was 11 and 21 days, respectively (p=0.01). The median time elapsed between biopsy and surgery in groups 1,2 and 3 centers was 14,1.5, and 12 days, respectively (p<0.05)., Conclusion: A high level of awareness regarding breast cancer in our country is related with the time that is defined as 10 days between disease recognition and medical application. The time elapsed between the application and biopsy, surgery and systemic therapy was longer compared with the corresponding figures in developed countries.

Background: This study evaluated whether prophylactic treatment with a cefazolin could prevent infections in patients who had a surgically inserted totally implantable venous access device (TIVAD)., Methods: We conducted a prospective, randomized, double-blind, placebo-controlled trial comparing wound infection rates in 404 patients (203 received prophylactic cefazolin, 201 received a placebo) undergoing TIVAD insertion. Infections were evaluated 3, 7, 14, and 30 days after discharge and outcomes were compared and analyzed., Results: Groups were well matched for all preoperative variables studied, including comorbid conditions. Superficial surgical site infection developed in 5 patients (2.5%) from the antibiotic group and 6 (3%) from the placebo group (P = .75). One from each group developed deep surgical site infection. Both patients were readmitted and underwent repeated debridement, which eventually resulted in port loss in 1 patient., Conclusions: We do not recommend the use of prophylactic antibiotics in TIVAD insertion because they will not decrease the already low rate of postoperative infectious complications. Registration number NCT00867295 (http://www.clinicaltrials.gov)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 S. Karger AG, Basel.)

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.

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.

It is not known how chemotherapy-induced cell death influences the size distribution of circulating free DNA (cf-DNA) in serum or plasma of cancer patients. In the present study, we investigated the integrity of cf-DNA during adjuvant systemic therapy in patients (n= 41) with invasive breast cancer. Sera taken at the beginning and the end of the adjuvant chemotherapy were comparatively analyzed for the integrity of cf-DNA. The assay was based on quantification of shorter and longer fragments representing apoptotic or non-apoptotic DNA from abundant genomic ALU repeats by quantitative real-time PCR. The ratio of longer to shorter fragments showed the integrity of free serum DNA. During chemotherapy, in half of the patients (51.2%), total DNA levels increased, but decreased in the other half. The distribution of the DNA integrity in the whole patient group after the systemic therapy (median 0.31) did not significantly differ from that at the beginning (median 0.29, P= 0.39). However, in the subgroups, the variation of the DNA integrity was related to the course of the total DNA level. In the subgroup with an increasing DNA level, the median DNA integrity was elevated from 0.27 to 0.39 (P= 0.005), whereas in the group with a decrease it declined from 0.34 to 0.28 (P= 0.044). Our results show that longer fragments released from non-apoptotic cells are the main contributors to increasing DNA levels during adjuvant systemic therapy. This information might be helpful in evaluating the response of patients to adjuvant systemic therapy.

Introduction: Hormone receptor negative breast cancer is encountered in about 30% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular markers in patients with receptor negative breast cancer., Methods: Tumor specimens from 140 patients with receptor negative (ER, PR) breast cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables were determined with respect to disease-free and overall survival., Results: Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and 47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK, respectively. Twenty-three patients with positive MAPK (16.4%) had a high level of expression (score 4-7) and 24 (17.1%) had a low score (1-3). A lower percentage of MAPK expression was significantly associated with a poorer OS (p = 0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for MAPK. Anthracycline resistance remained the only independent significant variable for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with recurrent disease, median survival after initial relapse was 16.8 months. MAPK was determined as the only prognostic factor for this endpoint. Patients with higher level of MAPK staining showed significantly shorter survival following initial recurrence (p = 0.04)., Conclusion: MAPK expression is a significant prognostic factor for non-metastatic patients with hormone receptor breast cancer. A lower level of staining is shown to be associated with with antracycline resistance and oveall survival, whereas a higher expression level is correlated with shorter survival following initial relapse, suggesting possible role of different molecular mechanisms pertaining to tumor progression once recurrence occurs. Further translational research is required to elucidate molecular mechanisms of the cross-talk between intracellular signaling and molecular pathways leading to drug resistance in patients with receptor negative breast cancer.

Objective: To evaluate the clinicopathological prognostic factors and outcome of chemotherapy in ovarian carcinosarcomas., Methods: We reviewed the records of 26 patients treated from 1990 to 2006 at the Oncology Institute of Istanbul University. Clinical data including demographics, stage, surgery, chemotherapy, and survival were collected from patients' charts., Results: All patients underwent initial debulking surgery. Optimal debulking was achieved in 21 (81%) patients. The most striking clinicopathological finding was the high incidence of hemorrhagic ascites (n: 6) which was observed in 60% of the patients with ascites (n: 10). The overall median survival of the patients was 26 months. Residual disease was associated with a decreased overall survival, P=0.04. Median survival (50 months vs 9.7 months, P=0.042) of the patients with early stage disease were longer than the patients with advanced stage. Twenty-two patients received platinum-based combination chemotherapy. There was a trend for increased median survival in the patients who were treated with carboplatin/paclitaxel combination (P=0.066). Although the numbers were insufficient for statistical evaluation, the patients treated with ifosfamide combinations had improved survival (36 months vs 26 months). However, when the patients treated with ifosfamide and carboplatin/paclitaxel combinations were combined, survival was statistically improved compared to the other regimens (36 months vs 9.7 months, P=0.04). Chemotherapy regimens containing doxorubicin or cyclophosphamide were not encouraging. Stage (P=0.02) and adjuvant platinum-based chemotherapy containing either paclitaxel or ifosfamide (P=0.024) remained predictive of outcome in the multivariate analysis., Conclusions: Hemorrhagic ascites can be used in the initial differential diagnosis of ovarian carcinosarcomas. Stage, optimal debulking and type of adjuvant therapy were statistically significant prognostic predictors of ovarian carcinosarcomas. We advise that patients with ovarian carcinosarcomas should be treated by optimal cytoreduction followed by adjuvant platinum/taxan or platinum/ifosfamide combinations.

Background: The integrity of circulating cell-free DNA (cf-DNA) in serum or plasma appears to be of diagnostic and prognostic value in cancer. Here, we investigated the dynamics of serum DNA levels and the size distribution of cf-DNA during adjuvant chemotherapy of patients with breast cancer (n=73)., Methods: By evaluating sera taken at the beginning and the end of the adjuvant chemotherapy, variations of serum DNA levels and the size distribution were analyzed, based on quantification of shorter apoptotic and longer non-apoptotic fragments from abundant genomic ALU fragments amplified by quantitative real-time PCR., Results: The mean DNA level did not change significantly during chemotherapy. However, individual cases revealed considerable variation in the amount of serum DNA. It increased in 43.8% of the patients, whereas it decreased in the remaining majority (56.2%). By calculating a "coefficient of variation" (both decrease and increase) in the level of total DNA and non-apoptotic DNA fragments, we compared the values at the beginning and the end of the therapy. For total DNA, the range was between 1.02- and 26-fold (mean 3.76-fold), whereas for non-apoptotic fragments it ranged from 1.01- to 73-fold (mean 6.9-fold) (p=0.033). In accordance with these findings, the integrity of serum DNA was higher in patients with increasing DNA levels and vice versa., Conclusions: Our findings suggest that non-apoptotic fragments contribute to a higher degree to the change of the DNA level during adjuvant chemotherapy.

Background: Dissemination of ovarian cancer occurs mainly within the peritoneal cavity and central nervous system involvement (CNS) is encountered rarely. This report describes an unusual case with iatrogenic leptomeningeal metastasis from ovarian carcinoma., Case: 36 year-old lady diagnosed with ovarian carcinoma develops neurologic symptoms 10 months following primary treatment. Medical history reveals a venticuloperitoneal shunt placement 16 years ago for non-communicating hydrocephalus. She undergoes surgery for obstruction of the VP catheter and pathologic evaluation reveals metastatic carcinoma consistent with the primary diagnosis. With subsequent systemic chemotherapy, the patient remains alive for 2 years., Conclusion: This report describes a unique patient with ovarian cancer, who developed iatrogenic leptomeningeal involvement of the lateral ventricule through an indwelling ventriculoperitoneal shunt.

Purpose: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy., Patients and Methods: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm)., Results: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities., Conclusion: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.

BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases. However, the vast majority of ovarian and breast cancer cases do not display the hereditary form of the disease. Estrogen-metabolizing genes may also contribute to the predisposition of breast or ovarian cancer. Polymorphic variants of the estrogen-metabolizing gene, CYP17, have been associated with the risk of hormone-related cancers. In this study we investigated the CYP17 polymorphisms in ovarian cancer patients harboring mutations in the BRCA1 and BRCA2 genes, patients displaying familial characteristics but not carrying mutations and patients with sporadic ovarian cancer. Association between the allele frequencies, the CYP17 genotype and tumor characteristics or clinical parameters was evaluated. Our data suggest evidence for an association between ovarian cancer risk and the CYP17 genotype in the subgroup of patients with familial disease in whom no mutations in the BRCA genes are found. Although there were no statistically significant differences in the genotype distribution between the control group and the subgroup of patients with BRCA mutations, the frequency of the CYP17 A2 allele was significantly higher in the subgroup of patients without BRCA mutations. We found a four- to eightfold higher risk in ovarian cancer patients with family history but without BRCA mutations. Our data indicate that the CYP17 A2 allele polymorphism may confer an increased risk and can provide a biomarker for ovarian cancer patients in whom no mutations in the BRCA genes are observed.

The association between glutathione S-transferase pi (GSTpi) and other clinicopathological parameters, response to chemotherapy and clinical outcome were investigated in chemotherapy naive epithelial ovarian cancer patients. Paraffin-embedded material from 55 patients were used for immunohistochemical analysis. All patients had received six cycles of cisplatinum-based chemotherapy and 41 of them were revalued by laparotomy. Pre- and post-chemotherapy GSTpi staining were detected in the cancer tissues of 18/55 (32.7%) and 5/14 (35.7%) patients, respectively. GSTpi expression was not associated with other clinicopathologic parameters. Of 17 patients with postoperative measurable residual disease clinical response was observed in 4/7 of GSTpi positive and in 9/10 GSTpi negative patients (p = 0.25). Pathologic complete response (pCR) was achieved in 5/8 of GSTpi positive and 11/22 of GSTpi negative cases (p = 0.69). There was no significant difference in overall survival and progression-free survival (PFS) according to initial GSTpi status. However the PFS of the five patients (median 22 +/- 5.9 months) who had postchemotherapy positive GSTpi was significantly shorter than the nine patients (10.0 +/- 2.19 months) who had negative GSTpi (p = 0.006). This difference was not observed in overall survival. These results suggest that initial immunohistochemical staining of GSTpi does not aid in the prediction of pCR and clinical outcome in patients with epithelial ovarian cancer. Nonetheless investigation of GSTpi expression after chemotherapy needs further evaluation.

Objective: The aim of this study is to evaluate the efficacy of intraperitoneal cisplatin as consolidation treatment in epithelian ovarian cancer patients with complete pathologic response following front-line platin-based chemotherapy., Patients and Methods: Thirty patients who had no evidence of disease as assessed by second-look laparotomy following chemotherapy for stage III epithelial ovarian cancer were given three courses of intraperitoneal cisplatin (100 mg/m(2)) with three weekly intervals as consolidation therapy., Results: Median age was 50 years. After a median follow-up period of 37 months, 16 patients are being followed with no evidence of disease. Eleven patients developed recurrent disease. Median disease-free survival was 50 months. Median overall survival is not reached. WHO grades 3-4 toxicity criteria were emesis in 19 patients (63.3%), abdominal pain in 5 (16.7%) and nephrotoxicity in 2 (6.7%) patients. Catheter-related complications were infection/peritonitis in one and catheter malfunction in one patient. There were no serious hematologic side effects that required transfusions or caused treatment delays. None of the patients developed serious neurologic toxicity. Treatment had to be stopped early in four patients who refused further treatment due to abdominal pain, nausea ::and vomiting. Dose reductions were required in five patients., Conclusion: Our results suggest that intraperitoneal cisplatin is a feasible regimen that may provide a favorable outcome in terms of progression-free survival in patients with a complete pathologic response following front-line treatment for ovarian cancer. Further randomized trials are required to evaluate the role of consolidation treatment in this setting.

Adult granulosa cell tumors of the ovary are rare neoplasms, accounting for less than 5% of all ovarian malignancies. In addition to the tumor stage, residual disease, patient age, tumor size, extent of surgery, and also some histologic factors have been reported to be of prognostic importance. Tumor registries were screened for all patients treated between 1979 and 1998 for ovarian tumors at the University of Istanbul. There were 952 ovarian carcinomas, of which 47 were granulosa cell tumors. All charts were reviewed, and the clinical data were extracted. Prognostic factors and treatment results were evaluated retrospectively. The median follow-up was 84 (range: 6-141 months) months. According to univariate analysis, there were only two significant factors for overall survival (OS): stage and presence of residual disease. The OS of the 23 patients with early stage (mean, 122 months; median, unreached) was significantly (p = 0.0001) better than the OS of the 22 patients with advanced stage (mean, 34 months; median, 21 months). A significant difference (p = 0.0004) in OS was also observed between patients with residual (mean, 42 months; median, 21 months) and nonresidual (mean, 108 months; median, unreached) disease. In a multivariate analysis, only stage remained statistically significant (p = 0.0001). The overall 5-year survival rate was 55% and median survival after recurrence was 21 months. Despite the small number of patients, the study showed that stage and macroscopic residual disease are significant prognostic factors. The benefit of chemotherapy and radiotherapy remains controversial.

This phase II study evaluates the efficacy and toxicity of a prolonged schedule second-line and third-line treatment of oral VP16 in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Twenty-two eligible women with progressive or relapsed ovarian cancer resistant to platinum-based therapy were included in this study. All the patients had received more than one prior treatment, and had evidence of disease progression within 6 months of the previous chemotherapy. Eleven patients had received more than two different chemotherapy regimens. Fifteen patients had received consolidation therapy with intraperitoneal cisplatin after an initial treatment course with six cycles of a platinum-based combination regimen. All patients with measurable disease observed in abdominal computed tomography scans were given oral VP16 at a daily dose of 50 mg/m2 for 14 consecutive days with 4 weekly intervals. Among 22 assessable patients, there were one complete response (CR) and three partial responses (PR), so the objective response rate, which is the addition of CR and PR rates, was 18%. Seven patients (32%) had stable disease. Median duration of response and stable disease was 2.5 months (range: 1-10 months). Overall median survival was 11 months from study entry (range: 3-36 months). Toxicity for most patients was mild, but a few severe myelotoxicities occurred, and there were no treatment-related deaths. According to World Health Organization toxicity criteria grade III/IV thrombocytopenia was seen in 4 of 22 patients, grade III/IV neutropenia in 6 of 22 patients, and grade III anemia was observed in 3 of 22 patients. Nonhematologic toxicity was mild, and mucositis was the most frequently observed nonhematologic toxicity. Oral etoposide has considerable activity with a tolerable toxicity profile for the treatment of platinum-resistant epithelial ovarian cancer.

The prognostic factors associated with local failure and overall survival and the effect of radiotherapy were determined in 77 patients with localized (extremity and nonextremity) operable soft-tissue sarcoma. There were 52 male and 25 female patients; median age was 50 years (range: 15-83). Histologic grade of the tumors was as follows: low-intermediate grade in 32 cases and high grade in 29 cases. The primary tumors were treated by marginal resection (20 patients), wide resection (52 patients), and radical resection (5 patients). Adjuvant radiotherapy was applied to 50 (65%) patients. The 5-year local recurrence-free survival rate was 70.6%. Treatment with adjuvant radiotherapy and development of metastases were the significant prognostic factors associated with local recurrence. Radiotherapy was more effective in patients with tumors 10 cm or larger, marginally resected, extremity located, and high grades. The overall survival rate was 64.4% at 5 years. Significant adverse prognostic factors were high grade tumors, presence of local recurrence, and development of metastases in univariate analyses. Development of metastases and old age were the only adverse prognostic factors by multivariate analysis. The best 5-year survival rate was obtained in female patients younger than 50 years (90%). The present study demonstrated the importance of adjuvant radiotherapy and development of metastases as prognostic factors for local control. Again, development of metastases and age were the most important prognostic factors in operable soft-tissue sarcomas.

The aim of this study is to identify the impact of various prognostic factors on survival in patients with recurrent carcinoma of the uterine cervix. Fifty-two patients who were treated with platinum-based chemotherapy for recurrent or metastatic disease were retrospectively evaluated. Twenty-seven patients (90%) had received pelvic radiation as primary treatment. Out of 45 evaluable patients, two (4.4%) had complete response (CR), three (6.7%) had a continuous CR after additional surgical treatment and irradiation. Five patients (11.1%) had partial response (PR). The majority of patients had progressive response to treatment (22 patients, 48.9%). After a median follow-up period of 19 months, 31 patients (60%) had died. Progression-free survival after initial diagnosis was observed to have a significant association with response to chemotherapy for recurrent disease (Fisher two-sided P = 0.027). The median survival duration for relapsed disease was 11.8 months. Those with a longer disease-free interval ( 8 months vs.

Objective: The objectives of this study were to evaluate the patients' characteristics and treatment results for 11 recurrent granulosa cell tumors (GCT) of the ovary., Methods: Tumor registries were screened retrospectively for all patients treated between 1979 and 1999 for ovarian tumors at the University of Istanbul. All information about these patients was obtained from operation, pathology, and follow-up reports. Then the clinical data were extracted. The patients were classified in stages according to FIGO criteria. There were 952 ovarian carcinomas, of which 45 were GCT. Eleven of 45 patients (24%) developed recurrent disease on follow-up., Results: All patients but one had advanced (III-IV) disease at diagnosis. The median progression-free interval (PFI) was 16 months (range, 5-39 months) with a marked difference in PFI between patients receiving (24 months) and not receiving (8 months) initial chemotherapy. Among patients received chemotherapy (six patients), two complete and two partial responses were observed, for an overall response rate of 67%. The median survival for all patients was 26 (4-73) months with a longer survival (38 versus 8 months) for patients retreated with a platinum-containing regimen., Conclusions: Despite the fact that small number of treated cases does not allow an adequate evaluation, retreatment with cis-platinum-containing regimens may be the treatment of choice for patients with recurrent disease.

The efficacy of a combination of cyclophosphamide and cisplatin in patients with metastatic and recurrent carcinoma of the cervix, was tested. Thirty patients were included in the study. Initially, 27 patients (90%) had received pelvic radiation and intracavitary boost and one patient was additionally given paraaortic radiation. Cisplatin was given at 75 mg/m2 followed by cyclophosphamide at 750 mg/m2 on day 1 with three weekly intervals for a maximum of six cycles. All patients received a median of four cycles of chemotherapy. The overall response rate for all eligible patients was 20% (continuous CR: 1, CR: 1, PR: 4 patients). Overall response rate and progressive response in patients with relapse within the previous radiation field were 9.5% and 66.7%, respectively; while for patients who had recurrent disease outside any irradiated area both were 44.4%. Eighteen patients (60%) had early withdrawal from the planned schedule, which was due to patient incompliance in seven patients (23.3%), disease progression in ten (33.3%) and early death after the first cycle in one patient (3.3%). Anemia was the most frequent toxicity, necessiating 24 transfusions in nine patients (30%). WHO grade 3 and 4 toxicity were anemia: 13 (43.3%), leucopenia: one (3.3%), thrombocytopenia: two (6.6%), renal: one, emesis: nine (30.0%) patients. The median survival duration for all eligible patients was 11 months. Univariate analysis revealed that progressive response to chemotherapy was the only prognostic factor for survival (7.1 vs 16.8 months, p = 0.003). The combination of cisplatin and cyclophosphamide did not appear to be more active than single agent cisplatin in this patient group with a relatively poor prognosis. Further studies are required to determine a better therapeutic approach for patients with relapsed carcinoma of the cervix.

Gastric carcinoma remains one of the leading causes of cancer-related death in the world. Clinical studies have revealed that approximately two thirds of the patients seek treatment for early recurrence within the abdominal cavity. The aim of this phase II study was to evaluate the toxicity, feasibility, and efficacy of adjuvant intraperitoneal chemotherapy (IPCT) with cisplatin, mitoxantrone, 5-fluorouracil (5-FU), and folinic acid in patients with stage II-III gastric cancer. Patients with stage II and III gastric cancer aged between 15 and 70 years, after curative resection, with adequate liver, renal, and cardiac function were included in the study. The chemotherapy regimen consisted of cisplatin 60 mg/m2, mitoxantrone 12 mg/m2, 5-FU 600 mg/m2, and folinic acid 60 mg/m2, delivered intraperitoneally, diluted in 2 l normal saline. Intraperitoneal fluid was not drained. Each course of IPCT was repeated every 4 weeks for a total 6 cycles. Thirty-nine patients were enrolled in the study. Twenty-eight of the 39 patients (71.8%) completed six courses of the planned schedule. One patient (2.6%) died after a fourth cycle of IPCT from an undetermined reason. The major nonhematologic toxicity from IPCT was grade I-III nausea and/or vomiting experienced by 27 patients (69.2%). Twenty-four (61.5%) patients reported abdominal discomfort. Median follow-up was 23 (range: 3-105) months. Twenty-five patients (64.1%) were dead. Median disease-free survival and overall survival were 12 (CI 95%; 8.3-15.7 months) and 19 months (CI 95%; 10.5-27.5 months), respectively. The cumulative 5-year disease-free survival and overall survival were 24.7% and 30.7%, respectively. The regimen was generally associated with acceptable toxicity. However, adjuvant IPCT has similar survival rates in comparison to no adjuvant treatment; thus, it cannot be currently recommended outside the context of a clinical trial.