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Introduction: we aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey. Material and methods: in this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity. Results: ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B- cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% (= 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%). Conclusions: objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy., NA

WOS: 000399505100004 PubMed ID: 28333566 Background: There are insufficient predictive markers for renal cell carcinoma (RCC). Methods: A total of 308 metastatic RCC patients were analyzed retrospectively. Results: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35months (p < .001) and 21.0 versus 11.36months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. Conclusions: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

e19027 Background: Bendamustine is an old conventional agent which is used in the treatment of hodgkin's lymphoma (HL), non-hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL) patients despite they are relapsed or refractory cases. In our study we wanted to reveal retrospectively the efficacy and side effects of bendamustine in relapse/refractory patients from Turkey. Methods: We included in the study relapse/refractory HL and NHL patients who underwent multiple line chemotherapy. Bendamustine was administered at 90 mg/m² on days 1 and 2, every 3 weeks by 60 minutes infusion. The primary endpoint of the study was to determine the objective response and toxicity. Results: Seventy-five patients (31 female) with a median age of 62.8 years (range 16-89 years) were included in the study. 58 of the patients were NHL (follicular lymphoma:8, diffuse large B-cell lymphoma: 17, mantle cell lymphoma: 11, marginal zone lymphoma: 4, Small lymphocytic lymphoma:11, Others:7) and 17 of them were HL patients. The patients were underwent median three lines chemotherapy (range 1-8) accept autologous stem cell transplantation, 20 patients (HL: 12, NHL:8) were underwent autologous stem cell transplantation. Bendamustine was performed an average of 6 cycles (range 1-38). The objective response rate was 73.3%, complete response rate was 44% (n = 33), partial response rate was 29.3% (n = 22), respectively. The response rate was 65% (11/17) in HL cases, 79% (30/38) in indolent NHL cases and 70% (14/20) in aggressive NHL cases. For median follow-up of 20.7 months, the median overall survival (OS) was 64.9 months, OS rate was 75.5% for 1 year, 67.6% for 2 years and 63.1% for 3 years. The most common side effects associated with treatment were lymphopenia, neutropenia, thrombocytopenia, abdominal pain, fatigue and diarrhea. Side effects which were seen as grade 3 and higher levels: 9.6% lymphopenia, thrombocytopenia 8% and 12% fatigue. Conclusions: Objective response rate of bendamustine with tolerable side effect profile was found to be 73.3% in relapsed / refractory HL and NHL patients as a rescue agent. It appears to be an ideal agent for rescue treatment which had previously received intensive treatment.

Trastuzumab emtansine (T-DM1), a novel drug developed for the treatment of HER2-positive breast cancer, is a human epidermal growth factor receptor (HER2) targeted antibody drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine). It has been shown that, in preclinical studies, it has anti-tumor activity in trastuzumab refractory cancer cells. In this review, we aim to show the clinical data about trastuzumab-DM1 (T-DM1) therapy and to discuss the therapy advantages for the management of patients with HER2-positive breast cancer.T-DM1 showed positive results in clinical studies of HER2-positive metastatic breast cancer. PubMed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched up to September 2012 by using the terms 'trastuzumab emtansine (T-DM1) and anti-HER2 treatment'; papers which were considered relevant for the aim of this review were selected by the authors.The phase III randomized trial EMILIA has shown that T-DM1 provided objective tumor responses and significantly improved progression free survival and overall survival compared to lapatinib and capacitabine combination in HER2-positive metastatic breast cancer patients treated with a prior taxane and trastuzumab regimen. It is believed that T-DM1 will play a role in the management of patients with advanced and early stage HER2-positive breast cancer, but this awaits further study. In particular, the ongoing phase III trials MARIANNE and TH3RESA will further give information about the place of T-DM1 in the treatment algorithms for HER2-positive disease.The trials of T-DM1 as a single agent and in combination with other chemotherapies have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. There are ongoing studies of T-DM1 showing an increasing tendency towards moving the study of these agents to earlier stages of HER2-positive breast cancer.

Lapatinib is a dual tyrosine kinase inhibitor (TKI) that has a considerable efficacy in ErbB2-positive metastatic breast cancer (MBC). Previous studies revealed that TKIs caused cardiotoxicity in approximately 10 % of the patients. This study assessed the cardiac safety of lapatinib in women with ErbB2-positive MBC. In this observational single center study, all patients with ErbB2-positive MBC who were previously treated with anthracycline, taxanes, and trastuzumab in the adjuvant and/or metastatic setting were assigned to receive lapatinib at a dose of 1,250 mg per day continuously plus capecitabine at a dose of 2,000 mg/m(2) in two divided doses on days 1 through 14 of a 21-day cycle. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography and biochemical markers (brain natriuretic peptide (BNP), creatine kinase (CK) and creatine kinase-MB) at baseline and every 9 weeks until disease progression. Twenty-six patients were treated with lapatinib and capecitabine therapy for a median of 18 (range 3-60) weeks. The median age was 48 (range 28-83) years. All patients had ErbB2-positive MBC. Among 25 eligible patients, 5 (19.2 %) patients experienced new cardiac events compared with baseline findings. Of these 5 patients, 1 (3.8 %) had T wave negativity, 1 (3.8 %) had sinus tachycardia, 1 (3.8 %) had grade 1 (453 ms) QT prolongation, and 2 (7.7 %) had decreased LVEF below the critical level. Among eligible 21 patients, 2 (7.7 %) had increased BNP, 1 (3.8 %) had increased CK, and 1 (3.8 %) had increased CK-MB level compared with baseline. No serious cardiac events that required monitorization or medication occurred. There was no statistically significant relationship between the duration of lapatinib administration and LVEF changes, QT prolongation, BNP, CK, and CK-MB level. According to our findings, lapatinib was safe and well tolerated and has a low incidence of cardiac side effects. Therefore, it seemed that cardiotoxicity was not a class effect of TKIs. However, despite the absence of clinically significant adverse cardiac effects under lapatinib therapy, the incidence of cardiotoxicity reported in our study was higher than previous lapatinib studies.

e11509 Background: Distant spread from breast cancer is commonly found in bones, lungs, liver, and central nervous system. However, peritoneal involvement is unusual and unexpected. The aim of the study was to perform a comprehensive analysis of breast cancer patients with peritoneal metastases. Methods: Twenty-one (0.9% of the cohort) breast cancer patients with peritoneal metastases were detected out of a database of 2,219 breast cancer patients treated in Hacettepe University Medical Oncology Department. Clinical characteristics, follow up times and survival rates were analyzed. Results: The mean age of the 21 patients at the time of peritoneal metastasis was 56 years (38-71). 12 (57.1%) patients were post-menopausal, 6 (28.6%) patients were pre-menopausal. Numbers of deceased patients were 7 (33.3%). Seven (33.3%) patients’ histological subtypes were invasive ductal carcinoma (IDC), five (23.8%) patients’ were invasive lobular carcinoma (ILC) and three (14.3%) patients’ were mixed (IDC and ILC). Numbers of luminal A patients were 8 (38.1%), luminal B were 5 (23.8%), triple negative were 2 (9.5%). There was no Her-2 overexpressing patient and numbers of unknown molecular subtype patients were 6 (28.6%). The median follow up times after peritoneal disease in patients deceased and living were 9.3 (range: 0.4-23.3) months and 15.6 (range: 0.3-40.4) months, respectively. Median follow up time after peritoneal metastasis of ER positive patients was 13.7 months, and it was longer than ER negative patients (4.4 months). Six months and one year survival rates after peritoneal metastasis were 83.3% and 73.3%, respectively. Disease free, progression free and overall survival data could not be obtained due to inadequate number of events. Conclusions: Peritoneal metastasis of breast cancer is very rare and median survival time is controversial in literature. Despite of a small cohort, we found the patients’ follow up times longer than reported before. Especially, ER positive patients have longer survival time than ER negative, and this result highlights the importance of hormonotherapies.

Background Breast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer. Methods This cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis. Results Thousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15–1.74; p =0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01–2.25; p =0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03–2.13; p =0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83–1.88; p =0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47–0.97; p =0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53–1.04; p =0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93–5.17; p =0.04) and luminal A (OR 1.87, 95% CI 0.93–3.90, p =0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06–3.37; p =0.04 and OR 1.90 95% CI 1.00–3.61; p =0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43–0.95; p =0.02 and OR 0.50 95% CI 0.32–0.76; p =0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands. Conclusions Reproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.

e11080 Background: Trastuzumab is an effective adjuvant targeted therapy in patients with HER-2 positive breast cancer. However, effect of this therapy on survival is not well described in literature. In this study, we aimed to show characteristics of patients treated with nine week trastuzumab therapy for breast cancer and survival analysis. Methods: We analyzed the data of 2.218 breast cancer patients treated and followed up in our medical oncology department. There were 165 patients treated with 9 weeks of adjuvant trastuzumab therapy in this cohort. Patients’ characteristics, prognostic factors, and survival data were analyzed by using SPSS 18.0 version. Results: The mean age of the patients at the time of diagnosis of breast cancer was 47.3 ± 10.0 years. Sixty two (37.6%) patients were postmenopausal, eighty two patients (49.7%) were premenopausal and twenty patients (12.1%) were peri-menopausal. Invasive ductal carcinoma was the most common pathological type and was observed in 87.9% of the patients. ER and PR was positive in 49.1% of the patients and 54.5 % of the patients, respectively. Percentage of stage of the patients was 10.9 in stage I, 21.1 in stage IIA, 17.6 in stage IIB, 21.2 in stage IIIA, 0.6 in stage IIIB, 23.6 in stage IIIC. Mean follow up time of the patients was 30.9 ± 13.4 months. Numbers of the patients with progression were eighteen (10.9%). Eight (4.8%) patients died due to disease progression. Two-year survival rate was 98.3%. Disease free, progression free and overall survival times could not be obtained due to inadequate number of events. Conclusions: The superiority of nine weeks of adjuvant trastuzumab therapy to standard one year regimen of adjuvant trastuzumab is not well described in literature. The studies comparing 9-weeks and one year of adjuvant trastuzumab use with large numbers of patients are needed to show which regimen is superior.

e11092 Background: Due to advances in treatment modalities and palliative care patients with breast cancer live longer compared to the past and thus encounter an increased risk for secondary cancers. This study aims at finding the frequency of other solid cancers in a retrospective cohort. Methods: A search for the history of a non-breast solid tumor (NBST) among 1914 women admitted to our institute with stage I to IV breast cancer between 2006 – 2012 was conducted. Frequency of NBST according to temporal relation with breast cancer diagnosis was calculated Results: Overall 79 NBST and 75 patients (3.9 %) with another solid tumor were discovered. Of the patients 4 had more than one tumor. For these patients the median age at diagnosis was 55 (28 – 93), median follow-up time for breast cancer was 32 months (1 – 132). Post-menopausality was 60.8 %. The most common breast cancer histology was infiltrative ductal carcinoma (70.9 %). Of the 79 NBST, 34 (43.0 %) were diagnosed after breast cancer; 30 (38.0 %) before; and 15 (19.0 %) synchronously. Median time of diagnosis for NBST after breast cancer was 21 months (7 – 296). The most common malignancies were cancers of the ovary, thyroid and uterus (17.7, 15.2 and 11.4 %, respectively). Conclusions: The frequency of gynecological cancers and thyroid cancer along the course of breast cancer is high. Common environmental and genetic factors and may be involved. These patients should be followed closely

e11041 Background: The majority of breast carcinomas are the luminal type, which has the higher levels of estrogen receptor, tend to be low grade with a favorable prognosis. Altered glycosylation, ...

1117 Background: Obesity is related with luminal type breast cancer. The aim of this study is to evaluate the association between body mass index (BMI) and breast cancer subtypes. Methods: 1,255 br...

e11001 Background: Lapatinib (L) is a tyrosine kinase inhibitor (TKI) that has efficacy in breast cancer. This study assessed the cardiac safety of lapatinib in women with cerbB-2 amplified metasta...

e11020 Background: Aromatase inhibitors (AIs), anastrozole (ANA) and letrozole (LET), have been shown to be more effective than tamoxifen in the adjuvant treatment of postmenopausal hormone receptor positive breast cancer. However, data from preclinical studies and subgroup analyses of some major clinical trials suggest differring efficacy among AIs. Yet the best clinical choice is still not very clear. This retrospective study aims at comparing the results of treatment with either AI among different subgroups of patients, especially among the obese patients. Methods: Between 2006-2011, 335 women with stage I to IIIC hormone receptor positive postmenopausal breast cancer treated with either ANA or LET as adjuvant treatment were included. Body mass index (BMI), estrogen and progesterone receptor (ER and PR) and HER-2 status at the time of diagnosis were recorded. Patients were grouped as BMI ≤ 30 and BMI > 30. The Kaplan-Meier survival estimates were calculated. Subgroups were compared with the log rank test. A 5 % type-I error was used to infer statistical significance. Results: The percentage of patients receiving ANA or LET were 47.2% and 57.8%, respectively. Median age at diagnosis was 58 (42-84) and lower in the ANA group (p=0.04). Stage II to IIIC disease was present in 76.8 % and the distribution was similar between ANA and LET (p=0.84). Median time of follow-up was 29 months (6-124) and median duration of hormonotherapy was 29 months (3-68) and similar between two groups (p=0.52 and p=0.55, respectively). Of the patients 41.2 % had a BMI of > 30. There was no significant difference in overall (OS) and progression-free (PFS) survivals between ANA and LET (p=0.08 and p=0.94, respectively). However, among patients with a BMI of > 30 a statistically insignificant benefit in PFS was observed with LET (p=0.1). ER, PR and HER2 status had no significant impact on OS and PFS. Conclusions: In a median follow-up of 29 months letrozole and anastrozole yielded similar OS and PFS. However, among patients with a BMI of > 30, LET might bring about a PFS advantage. In selected obese patients LET might be a reasonable choice in this setting. Larger studies with long term follow-up are needed to reach an exact conclusion.