e12007 Background: Breast cancer is the most common cancer among women in Turkey. The risk factors and characteristics of breast cancer patients have not been widely studied in Turkish population. In this observational study we planned to define the disease characteristics and the role of risk factors of patients with early breast cancer in Turkey. We present the results of the interim analysis of an ongoing study of Turkish Oncology Group. Methods: This is a nation-wide cross-sectional study of patients with early breast cancer. A total of 3.000 patients with newly diagnosed breast cancer at the 35 centers between March 2008 and March 2011 were planned to be included in the study. In this report we present the results of 2350 patients whom records were available at the time of analysis. Results: The median age was 49 years (range: 22 - 86). The 47% of the patients were post-menopausal and 53% pre-menopausal. The median age at menarche (13 years) and at menopause (48 years), the rate of smoking (12.1% current), alcohol (1.7%), hormonal contraception use (14.5%) were similar to the general female population. Among the studied environmental risk factors, the ratio of use of computerized tomography of abdomen/chest during adolescent period was worrisome in this cohort of breast cancer patients (15.4%). Likewise, the ratio of important stress (death of child/husband/parent) within past 10 years was enormously high (28.4%). The history of previous breast cancer was 0.6% and the family history of breast cancer 19.9%. The major histologic type was invasive ductal cancer (82.9%). The rate of axillary negative patients was 59.1% and T1 tumors 45.1%. ER positivity was 71.7% and c-erbB-2 overexpression 19.7%. Conclusions: Although it is needed to be clarified, the very high rate of history of use of computerized tomography during adolescent period in this study underlines the possible role of diagnostic radiation exposure during childhood in carcinogenesis. Likewise, important stress within 10 years of diagnosis seems to be an important risk factor. We believe that the breast cancer awareness campaigns have changed the disease characteristics of patients with breast cancer in Turkey.

PURPOSE:The metastatic lymph node ratio (LNR) is defined as the number of metastatic lymph nodes divided by the total number of lymph nodes removed. The aim of this study was to investigate the prognostic significance of the metastatic LNR in patients with colon cancer.METHODS:One-hundred twenty-five patients with stage III colon cancer admitted to the Istanbul University Oncology Institute between 1995 and 2005 were retrospectively evaluated. The median LNR was 0.2, and this figure was accepted as cut-off value in the present study. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. Log-rank test was used for intergroup comparisons. The significance level was put at p<0.05.RESULTS:Of the 125 patients, 58 (46.4%) were males and 67 (53.6%) females with median age 57 years. The mean OS in patients with a LNR <0.2 was 120.5±7.3 months, with a LNR ≥0.2 was 92.8±9.0 months Although clinically significant, the difference between the groups was statistically insignificant (p=0.074). The mean duration of DFS in patients with a LNR <0.2 was 100.6±8.6 months and for those with a LNR ≥0.2 it was 71.7±8.3 months (p=0.017). The 5-year DFS rate in patients with a LNR ≥0.2 was 42.3%; it was 64.1% in those with LNR<0.2. The difference between the groups was statistically significant (p=0.017).CONCLUSION:The determination of the optimal cut-off value for the LNR in future prospective studies will help defining prognosis with better accuracy in colon cancer patients.

10539 Background: The aim of this study is to investigate the effect of change in expression levels of survivin, glutathione-S-transferase P1 (GSTP1) and topoisomerase 2 alpha (TOP2A) on response to NAC consisting of 4 cycles doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) followed by 4 cycles docetaxel (100 mg/m2) ± trastuzumab. Methods: Tumoral expression of markers obtained before CT, after 4 cycles of AC and completion of CT, were analyzed by real-time PCR. Survivin expressions were additionally analyzed in serial blood samples. Results: The median age of pts (n=32) was 48 (28-75) yrs and median follow-up was 36.3±12.5 months (9.4-53.6). The majority of pts had clinical stage T3-T4 (n=23, 72%), clinically lymph node positive (n=29, 91%), grade III (n=23, 72%), ER positive (n=17, 53%), PgR positive (n=21, 66%), and HER-2 negative (n=27, 84%) disease. 14 pts (43.8%) developed recurrence and 6 pts (18.8%) died during follow-up. The median PFS was 29.3±14.5 months. The table shows changes in serial expression levels of markers analyzed. Serial GSTP1 expression in pts with clinical partial and complete response (CR) decreased from 1.41 to 0.33 and to 0.19 (p:0.0001). In addition, expression levels in pts with a pathological CR in breast and axilla were 1.85, 0.33 and 0.28 (p:0.0001). Anthracycline-related decrease in GSTP1 expression was determined as the only independent prognostic variable for PFS (p=0.01). Nevertheless, there was not correlation between survivin and TOP2A expression and clinicopathologic parameters, response, and survival. Conclusions: Downregulation of GSTP1 is a significant predictor of pCR and improved PFS during anthracycline and taxane-based NAC for pts with LABC. Monitoring GSTP1 expression levels may be used as an early predictor for response to NAC in LABC pts. Expression levels of markers during treatment (median ± SD). Before CT After four cycles CT After eight cycles CT p GSTP1 2.30±59.7 0.34±25.2 0.24±2.9 0.014 TOP2A 0.27±1.3 0.27±3.8 0.14±0.8 NS Survivin 0.93±5 0.16±3.8 0.19±0.2 NS Survivin in blood 0.87±2.5 0.86±4.8 0.55±2.5 NS

PURPOSE:The molecular mechanisms related to colorectal carcinogenesis are controversial. The purpose of this study was to evaluate the possible role of high-risk oncogenic human papillomavirus (HPV) types in the pathogenesis of colorectal cancer.PATIENTS AND METHODS:Tumor, and corresponding normal mucosal tissue specimens were obtained soon after surgery from 56 patients with colorectal adenocarcinoma. We studied both neoplastic and normal colon tissues for the presence of HPV types 6, 11, 16, 18, and 33. After the isolation of DNA, the presence of specific types of HPV DNA was determined by polymerase chain reaction (PCR) and southern blot hybridization.RESULTS:HPV DNA was detected in 46 (82.14 %) of 56 colorectal adenocarcinomas and in 18 (32 %) of 56 normal colonic mucosal tissue samples. Two or more HPV types were detected in 32 carcinoma samples. HPV type 18 (n= 40) and 33 (n= 32) were the most frequently detected types of HPVs in the tumor tissues. None of the normal mucosal specimens revealed HPV 18 DNA. The expression rate of HPV DNA in tumor tissue was significantly higher than that encountered in normal colonic mucosa (p <0.001).CONCLUSION:Detection of HPV DNA types 18 and 33 in most of the colorectal adenocarcinoma specimens suggests that HPVs may be related to carcinogenesis in glandular cells of the colorectal mucosa of our patient population.

In order to investigate the effect of kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we monitored the systemic immune response by measurement of the serum proinflammatory cytokine levels and we evaluated the anti-microbial effect of kefir with an agar diffusion method. Forty patients with colorectal cancer were included in this randomized prospective study. On the first 5 days of each CT cycle, the study group received oral lavage with kefir and then swallowed 250 ml of kefir while control group received oral lavage with 0.09% NaCl twice a day. Before and after every cycle of CT, the oral mucosa was assessed. Serum proinflammatory cytokine levels were evaluated before the initiation and after the third and the sixth cycle. Kefir was administered in 99 out of 205 courses. Mucositis developed in 27.3% of the courses given with kefir administration and in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between the two groups was not statistically significant (p > 0.05). When we compared the serum proinflammatory cytokine levels of the two groups at the baseline and following the third and the sixth cycles, we again found no statistically significant difference (p > 0.05). Kefir consumption at the mentioned doses made no statistically significant effect on serum proinflammatory cytokine levels and on the incidence of mucositis development in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus epidermidis.

11563 Background: The efficacy of hormone therapy (HT) is controversial in patients with a lower level of estrogen receptor (ER) expression or absence of progesterone receptor (PR). The aim of this study is to compare the efficacy of adjuvant HT and chemotherapy (CT) +HT in patients with different levels of ER and PR expression. Methods: 190 patients with nonmetastatic hormone responsive breast cancer and a median follow-up period of 49 months were included in this study. Fifty percent of patients were premenopausal and 63% were node positive. Both HR were evaluated by immunohistochemistry. ER expression score, as assessed by the ratio or percentage of cells stained positive, was evaluated in 4 groups: negative (8%), <1/3 (29%), ≥1/3–2/3 (18%), >2/3 (45%); whereas, patients were classified as positive or negative (19%) with respect to PR expression. The number of patients who received CT/HT and HT in the high ER score group and ER+/PR- groups were 63 (77%)/19 (23%) and 27 (82%)/6 (18%), as compared to low ER 44 (83%)/9 (17) and ER+/PR+ groups 121 (81%)/7 (21%), respectively. The prognostic impact of these factors on overall (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. Results: The use of adjuvant CT was significantly higher in patients with node positive disease regardless of ER score or PR expression. OS and DFS were significantly lower in patients with a negative ER (p=0.02). There was no difference in either endpoint with respect to expression score. There was a trend for poorer DFS and OS (p=0.08) in PR negative patients. There was no additional efficacy of CT with respect to ER score or PR expression. Conclusions: In this data set adjuvant CT seems to offer no additional benefit in ER positive patients regardless of ER score of PR expression. Other factors should be evaluated to predict endocrine resistance in patients with hormone responsive disease. Mature data with longer follow-up is pending. No significant financial relationships to disclose.

16516 Background: To determine the outcomes of patients with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CCC) of the endometrium treated in Turkey. Methods: 191 patients with UPSC and CCC, treated in 9 university oncology centers around Turkey between 1991–2007 were analysed retrospectively. Results: Median age was 65 years (29–85yrs). FIGO Stage was IA in 10, IB in 38, IC in 30, IIA in 13, IIB in 26, IIIA in 27, IIIB in 4, IIIC in 41, and IV in 2 patients. 93 patients had UPSC, 91 had CCC, and 7 had UPSC and CCC. 77% of patients had complete surgery, while surgery was incomplete in 41. 2 patients (1%) were medically inoperable. Treatment included radiotherapy (RT) alone (120), chemotherapy (CT) alone (14), CT and RT (46), and none (11). RT was administered as external alone (ERT) in 27%, intravaginal brachitherapy (IBT) alone in 12%, ERT and IBT in 48% of patients, and 13 patients didn’t receive any RT. 14% of stage I, 26% of II, 53% of III patients had CT. Median follow-up was 27 months (3–189). Five-year overall (OS) and disease-free survival (DFS) rates were 61% and 55%. OS was significantly better in younger patients, with early stages and patients receiving RT. There were no survival difference for receiving CT or completeness of surgery when adjusted for stage. Surgery was incomplete in patients with early stage disease, while advanced disease was completely resected in our patient group (p=0.028). A significant difference in recurrence site was seen in patients treated in adjuvant setting between the types of tretment (p<0.001) and types of RT (p=0.001). Conclusions: Administration of ERT with IBT appears to decrease the rate of locoregional recurrences significantly. Positive impact of CT or complete surgical debulking on survival were not shown in this study. These factors need to be further evaluated with prospective studies in this rare but aggressive types of endometrial carcinoma. No significant financial relationships to disclose.

21152 Background: Small cell lung cancer (SCLC) has a rapid growth rate, and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre and post treatment serum VEGF and its receptors Flt-1 and Kdr levels in SCLC patients have impact on clinical outcome is unknown. Methods: From February 2001- January 2003, 39 consecutive patients (34 male, 5 female) with histologically proven SCLC were enrolled into the study. The patients were staged as limited and extensive according to the Veterans Administration Lung Group (VALSG). Pre treatment (n:39) and post treatment (n:25) serum samples of the same patients after 3 months of treatment were collected. The levels of VEGF and its receptors Flt-1 and kdr are measured in the serum by quantitative sandwich enzyme immunoassay technique. Statistical analysis was performed using the SPSS 10.0 pocket program. Results: The median pretreatment serum VEGF, Flt-1, and Kdr levels were 1,200 pg/ml (range, 1,414.3±956.2 pg/ml), 85 pg/ml (range, 97.8±70.7 pg/ml), and 11,550 pg/ml (range, 14,481±6,267 pg/ml) respectively. The pretreatment serum VEGF, Flt-1, and Kdr concentrations were not different in limited and extensive stages. We detected a poor but positive correlation between VEGF and Kdr (r=0.46, p=0.003). Pretreatment low serum VEGF value (<728.5 pg/ml) and good response to treatment were found as good prognostic factors in multivariate analysis. Surveillance of serum VEGF and Flt-1, Kdr values did not correlate with clinical parameters. Conclusions: Serum VEGF was found to be a significant and independent prognostic factor in SCLC patients. We showed a limited association between serum levels of VEGF and Kdr. Whether the levels of serum VEGF and its receptors Flt-1 and kdr have value in detecting treatment modalities of SCLC needs further studies. No significant financial relationships to disclose.

BACKGROUND Triple-negative breast cancer is estimated to account for 15%-20% 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 factors in patients with triple-negative breast cancer. PATIENTS AND METHODS Tumor specimens from 109 patients with receptor-negative (estrogen receptor and progesterone receptor) breast cancer were analyzed for mitogen-activated protein kinase (MAPK), epidermal growth factor receptor (EGFR) and phosphoinositol-3-kinase (PI3K) expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables, was investigated. RESULTS Fifteen (13.8%), 38 (34.9%) and 33 patients (30.3%) had positive staining for EGFR, MAPK and PI3K, respectively. MAPK was associated with anthracycline resistance (P = 0.008) and lower MAPK score was significantly associated with shorter disease-free survival (P = 0.029). Survival following relapse was significantly worse for those with a higher MAPK score (P = 0.03). CONCLUSION MAPK is a significant prognostic and predictive factor in patients with triple-negative breast cancer. Furthermore, the level of staining among those with a positive MAPK expression may play a prognostic role at different stages of relapse. Further translational research is required to elucidate molecular mechanisms of tumor proliferation in this subset of patients.

The present study was designed to assess the efficacy and safety of combination therapy with temozolomide plus cisplatin in patients with metastatic melanoma. Thirty patients with metastatic melanoma were enrolled. Treatment consisted of intravenous cisplatin (75 mg/m(2)) on day 1 and oral temozolomide (200 mg/m(2)) on days 1 to 5, every 4 weeks. Nine patients (30.0%) achieved an objective response, including two complete (6.7%) and seven partial (23.3%) responses. The median response duration was 161 days. The median progression-free and overall survival times were 72 and 120 days, respectively. Myelosuppression and emesis were the primary toxicities. In conclusion, temozolomide combined with cisplatin is an active and safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.

A study was undertaken to analyze the extent of using complementary alternative medicine (CAM) and to compare sociodemographic and medical characteristics of users and non-users of CAM in Turkish oncology patients. A total of 615 patients with cancer who attended ambulatory patient care units answered the questionnaires. Medical information was reviewed from chart data. Some 291 patients (47.3%) had used at least one type of CAM since the time of initial diagnosis. CAMs almost always consisted of herbal agents (95%). Nettle (Urticae herba) used in conjunction with (88%) or without (56%) various herbal agents were the most popular and prominent CAMs used by patients. Univariate and multivariate comparisons of users and non-users of CAM were performed. In multivariate analysis, female sex (p=0.0006), high income (p=0.0008), advanced stage at diagnosis (p=0.02), and usage of multiple chemotherapy applications (p=0.03) were determined as independent factors for CAM use.

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.

This study was conducted to investigate the serum levels of bcl-2 and survivin in patients with melanoma and the relationship with tumour progression and known prognostic parameters. Forty-four patients with cutaneous melanoma were investigated. Serum samples were obtained on first admission before adjuvant and metastatic treatment were given and at follow-up. Serum bcl-2 and survivin levels were determined using enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA). The baseline serum bcl-2 levels were significantly higher in patients with melanoma than in the control group (P=0.01). For the serum survivin levels, no difference was found (P=0.6). No significant correlations were found between the prognostic parameters analysed and the serum survivin concentrations. The same was true of the serum bcl-2 values, except for the age of the patient (P=0.025) and nodal involvement (P=0.003). No significant relationship was found between the serum levels of bcl-2 and survivin (r=−0.13, P=0.4). In node-positive patients (n=8) both of these anti-apoptotic substances were unchanged after interferon-alpha-2b therapy. However, serum survivin concentrations were significantly increased in 10 patients with metastatic melanoma who underwent dacarbazine (DTIC)-based cytotoxic chemotherapy (P=0.047). A similar finding was not determined for the serum bcl-2 levels. In conclusion, the results of this study suggest that decreased apoptosis is associated partly with an increase in serum bcl-2. However, much research continues in this field, and exciting new knowledge will ultimately emerge.

5133 Background: Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results. The objective of this study was to determine whether hereditary Turkish ovarian cancer patients have distinct clinical features and outcome compared with sporadic cases. Methods: Eighy-seven concecutive epithelial ovarian cancer patients were genotyped for BRCA mutations between 1995–1999 years. Seventeen (19.5%) of these had germline mutations. Clinical and survival data of these patients were recorded. Results: No significant difference was found between the sporadic and mutated group in terms of stage, surgical outcome and histopathology. There were more patients under 50 years among the mutated group 13/17 (76% )than the sporadic group 32/70 (46%) p=0.03. The median overall and progression free survivals were 76 and 30 months in the mutated group and 80 and 33 months in the sporadic group respectively. Conclusions: Although the mutated ovarian cancer patients are much younger, no significant survival difference was observed between the groups. No significant financial relationships to disclose.

Serum protein S100 and melanoma-inhibitory protein (MIA) have been described as useful tumor markers for malignant melanoma. In this study, these two serum proteins were compared in 48 patients with melanoma at different stages of disease. Serum concentrations of S 100 and MIA were measured by immunoradiometric and enzyme-linked immunosorbent assays, respectively. We found that the cut-off values were 17.4 ng/ml for MIA and 0.09 mug/l for S100. Five patients had stage I-II, 22 had stage III, and 21 had stage IV disease. Serum levels of two markers were elevated with metastatic disease (p < 0.05). Sensitivities of the MIA were found higher compared with S100 in patients with extensive (M1c) metastatic disease and with chemotherapy nonresponders (p > 0.05). We showed a trend for worsened outcome in patients with elevated MIA level in univariate analysis. MIA was found to be more sensitive and is a potential prognostic marker for patients with metastatic malignant melanoma in comparison with S100.

7270 Background: The aim of this study is to evaluate the efficacy of an induction regimen consisting of carboplatin and weekly paclitaxel followed by concomitant chemotherapy and thoracic irradiation in patients with NSCLC. Methods: Twenty-four patients with stage III NSCLC, who were not amenable to curative surgery and ECOG PS ≤2 were administered an induction combination consisting of carboplatin at an AUC 6 mg.ml/min on D1 and 21 and weekly paclitaxel at 100 mg/m2 for 5 consequtive weeks starting on D1.Those without evidence of progressive disease in the form of metastatic involvement were given thoracic irradiation starting on day 50, reaching a total dose of 60 Gy with 180 cGy daily fractions for 5 weeks and an accelerated boost of 150 cGy/fr delivered to the tumor area over the last two weeks. Paclitaxel was given concurrently during irradiation at 60 mg/m2 on days 50, 57, 64,71 and 78. The median age of the patient group was 51.5 years, (37–71). Nine patients (37.5%) had an ECOG PS of 0, while the remaining 15 had a PS of 1. The majority had squamous cell histology (n=13, 54.2%), and 9 patients had adenocarcinoma (37.5%).Results: After a median follow-up period of 9 (1–25) months, 13 patients experienced progression (54.2%), 5 of which progressed while on treatment and eight patients (33.3%) died. Two patients did not complete the planned treatment schedule; 1 patient had an anaphylactic reaction to paclitaxel infusion and the other withdrew consent. Overall response rate after completion of the protocol was 62.5% (2: complete response, 13: partial response). The most frequent side effect of concomitant chemoradiation was oesaphagitis, encountered in 16 patients. Grade 3–4 toxicity during both phases of treatment were: oesaphagitis in 4 patients (16.7%), mucositis in 1 (4.2%), anemia in 1 and neutropenia in 1 patient. Conclusions: This treatment protocol consisting of an induction combination followed by concomitant chemoradiation is a feasible regimen with a tolerable toxicity profile in patients with locally advanced NSCLC. No significant financial relationships to disclose.

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 method. 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. (C) 2003 Elsevier Inc. All rights reserved.