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11066 Background: TLR4 is typically activated by gram (-) bacterial lipopolysaccharide; however, recent reports describe that paclitaxel could trigger the TLR4 signaling pathway leading to chemothe...

e22088 Background: Toll-like receptor role in tumor pathogenesis has been largely proven. Our purpose was to determine the differences of TLRs (TLR1 - TLR10) expression in 7 types of malignant tumo...

LBA505 Background: Premature ovarian failure (POF) is a common toxicity of CT. Risk depends on type and amount of CT, age, and perhaps ovarian cycling at the time of CT. POEMS is a SWOG-coordinated phase III randomized study to evaluate whether LHRH analog administration with CT for early-stage breast cancer (BC) would reduce POF. Methods: Premenopausal patients (PT) age .05). POF rates were 22% in the standard arm and 8% in the GN arm (OR=0.30, 95% CI: 0.10-0.87, p=.03 [unadjusted analysis]; OR=0.36, 95%CI: 0.11-1.14, p=0.08 [adjusted logistic regression analysis]). In a sensitivity analysis defining 2-year POF more liberally as either amenorrhea or elevated FSH, 45% in the standard arm and 20% in the GN arm had POF (OR=0.29, 95% CI: 0.12-0.70, p=.006). There were 13 pregnancies in the standard arm and 22 in the GN arm (OR=2.22, 95% CI: 1.00-4.92, p=.05). DFS and OS were better in the GN arm (Cox regression, including stage: HR=0.49, 95% CI: 0.24-0.97, p=.04; HR=0.43, 95% CI: 0.18-1.00, p=.05, respectively). Conclusions: LHRH analog administration with CT was associated with less POF and more pregnancies. In an exploratory analysis, GN use in premenopausal ER-negative BC was associated with improved DFS and OS. Clinical trial information: NCT00068601.

e12570 Background: Breast cancer (BC) is the second most common malignancy and the leading cause of death by cancer in Peruvian women (age-standarized rate [ASR] of 34 new cases/100,000 women estimated by GLOBOCAN 2008). The purpose of this study was to assess the incidence of BCin acohort ofwomenat Oncosalud, an oncologic pre-paid system that currently has 600,000 affiliates. Methods: We evaluated a dynamic cohort (period 1989 to 2011) of women affiliatedat Oncosalud – AUNA, an oncologic prepaid system.The crude incidence rate per year (number of new cases/women at risk), the specific rate according to age (number of new cases / persons-year) and cumulative risk were calculated. Results: Overall, during the assessment period, the BC incidence rate per year was 175.6 and the ASR incidence was 111.9 per 100,000 affiliates respectively. In our cohort of affiliates there were no BC cases before 1993 (with 907 women at risk for that year). The highest incidence rate was 177.6 registered in 1997 (11,822 women at risk). Incidence rates started decreasing in 2003 (169.2 with a population at risk of 39,593 women). The lowest incidence was 71.5, registered in 2011 (279,680 women at risk).According to age-groups, there were no BC cases under20 years old. Specificincidence ratesper age-group increases from the 30 year old-group (55.8). The peak of BC incidence was between 70 to 74 years old (407.4). In the same way, the cumulative risk increases after 30 years old. Conclusions: In our cohort of affiliates, the incidence of BC is greater than the general population, it could be due to the process of negative selection; however, specific incidence rates per age-group and cumulative risk are increased after 30 years, as seen in the general population.

e22165 Background: To evaluate toll-like receptors (TLRs1-9) and IRAK 1,3 and 4 expression in a breast cancer patients dataset that were treated with NAC as prognostic factors in terms of recurrence-free survival (RFS). Methods: Weretrieved normalized gene expression data from a public database (GEO: GSE25066) that includes 253 samples of breast cancer patients treated with NAC (antracyclines/taxanes) profiled with the U133A microarray. The median of RFS was 3.2 years (52 relapses observed). Distribution of molecular subtypes was: Luminal A (31.2%), Luminal B (17.4%), HER2 (7.1%), Basal (36.4%) and Normal (7.9%). We build a ratio of target gene/reference gen (ATCB) with to obtain replicable cut-points in other datasets. Levels of Gene expression were divided in three cut-points (Q1, Q2, and Q3). A cox-model was used to select gene expression cut-points with significant effects in the RFS. Results: According to molecular subtypes, there were significant differences in expression of TLR5 (higher in basal and Luminal A), TLR6 and IRAK1 (higher in basal and HER2). There were not differences of expression according to the pathologic response. The multivariate analysis shown that genes associated with the RFS were: TLR5 (HR=2.1 for the lower quartile), TLR6 (HR=2.4 for upper Q2), IRAK1 (HR=2.0 for upper quartile) and IRAK 3 (HR=2.2 for upper Q2). A TLR-Score was constructed (1 point added for each unfavorable gene-group). Cases were grouped in two categories (score 0-1 as good prognostic and score ≥ 2 as poor prognostic). There were and overall significant differences in both score-groups (poor prognostic: HR=4.9). In Basal and luminal B tumors there were significant differences (logrank test: P

e12566 Background: Prostate cancer (PC) is the most common malignancy and the leading cause of death by cancer in Peruvian men (age-standardized rate [ASR] of 37 new cases/100,000 men estimated by GLOBOCAN 2008). The purpose of this study was to assess the incidence of PC in a cohort of men at Oncosalud, an oncologic pre-paid system that currently has 600,000 affiliates. Methods: We evaluated a dynamic cohort (period 1989 to 2011) of men affiliated to Oncosalud – Auna, an oncologic prepaid system.The crude incidence rate per year (number of new cases/men at risk), the specific rate according to age (number of new cases / persons-year), and cumulative risk were calculated. Results: Overall, during the assessment period, the PC incidence rate per year was 183.7 and the ASR incidence was 145 per 100,000 affiliates respectively. In our cohort of affiliates there were no PC cases before 1995 (with 3061 men at risk for that year). The highest incidence rate was 160.5 registered in 1999 (12,461men at risk). Incidence rates showed a decreasing tendency since 2008 (159.7 with a population at risk of 86,408 men), reaching its lowest value in 2011(92.3 with 213,531men at risk). According to age-groups, there were no PC cases under 35 years old except for the 20-24 year old group (incidence rate 2.3). Specific incidence rates per age-group increases from the 40 year old-group (38.5). The peak of PC incidence was between 75 to 79 years old (1506.05). In the same way, the cumulative risk increases after 40 years old. Conclusions: In our cohort of affiliates, the incidence of PC is greater than the general population, it could be due to the process of negative selection; on the other hand, specific incidence rates per age-group and cumulative risk are increased after 40 years, as seen in the general population.

2097 Background: Survival after the onset of metastases in the central nervous system is very short. However, some variables could indicate subsets of worse prognosis. Our aim was to determine the value of clinicopathological characteristics and prognostic scores in the post-SNC recurrence survival. Methods: We evaluated a retrospective cohort of 2597 breast cancer patients treated at the Instituto Nacional de Enfermedades Neoplasicas (Lima-Peru) between 2000-2005. Clinicopathological data was retrieved, RPA and GPA brain metastases prognostic scores were constructed and phenotypes were categorized according to the IHC expression in [HR+,HER2-], [Any HR, HER2+] and Triple Negative. Survival was calculated according to the Kaplan Meier methodology and cases were stratified by variables evaluated. The log-rank or Breslow tests were used when appropriate and multivariate analysis was done by the cox regression. A P

e11518 Background: CNS relapse in breast cancer patients is invariably defined as a poor prognosis feature with varied and bizarre clinical presentation. We describe the commonest signs and symptoms in CNS relapse and their relation with prognosis Methods: We evaluate retrospectively 2597 women with breast cancer treated at the Instituto Nacional de Enfermedades Neoplásicas (Lima-Perú) between 2000-2005. Phenotypes were determined by IHC and categorized in [HR+, HER2-], triple-negative (TN) [HR-, HER2-] and Her-2 [HR+/-, HER2 +]. Post-CNS recurrence survival was calculated by Kaplan Meier method. We use Chi-square, or exact Fisher test when appropriate, to evaluate correlations between categorical variables. Results: 157 pts (6.04%) had CNS relapse from which 19 had only leptomeningeal carcinomatosis (LMC), 124 only brain metastases and 14 both. In regard to phenotype, 43pts were [HR+, HER2-] (5 LMC), 68 were TN (13 LMC) and 51 were [HR+/-, HER2 +] (15 LMC). 152 pts had stages I-III (96.8% of all SNC relapses). There was no association between phenotypes and age at CNS relapse, ECOG PS, extracraneal metastases, control of primary tumor, number or volume of brain metastases. Significant association was found between phenotype and time from diagnosis to CNS relapse (≤8 months: 16.3% in TN, 7.3% in Her-2 and 0% for [HR+, HER2-], [P=0.017] ) and histological grade (grade III: 74.4% in TN, 55.% in Her-2 and 30% for [HR+, HER2-], [P=0.006]). Symptoms/signs frequently described in LMC patients were cephalea (72%), meningism (24%), nausea (24%), vomiting (20%), ataxia (20%), facial palsy (16%), somnolence (16%), paraparesia (12%), hiporeflexia (12%), apraxia (12%), arreflexia (12%), poor sphincter control (12%), hemiparesia (8%), seizures (8%), bradipsiquia (8%), neuropathic pain (4%). Fifty percent of TN pts with LMC had meningism. Post recurrence survival was shorter in TN patients (3.61mo vs 4.89mo to [HR+, HER2-] vs 5.95mo to [HR+/-, HER2 +; P=0.044] and in patients with meningism (1.38mo vs 5.26mo; P=0.02). Cox regression identify meningism as a risk factor for survival in patients relapsed with LMC (HR: 4.33; P=0.066). Conclusions: Meningism seems to be the only sign related to poor prognosis in patients relapsed with LMC.

e15036 Background: The IGCCCG classification, used to guide the management of metastatic seminomas may underestimate the predictive value of other prognostic factors. We aimed to identify prognostic factors for long term survival in patients with advanced testicular seminoma who achieved a complete response to first line cisplatin based chemotherapy. Methods: A retrospective analysis was carried out on 101 patients with advanced testicular seminoma who received induction cisplatin based chemotherapy between 1990 and 2010.Data regarding clinical and laboratory parameters that may influence the overall survival (OS) or progression free survival (PFS) were collected from clinical records. Univariate analysis was performed using the Kaplan-Meier method, while Cox regression modeling was used for multivariate analysis. Results: The mean follow up time was 8.4 years. 9 (9%) patients died and 16 (16%) developed relapse. The 10 year OS and PFS rates were 91% and 84%. In univariate analysis, a testicular tumor ≥5.5cm and a retroperitoneal metastases ≥16 cm were associated with poor OS and PFS. The prechemotherapy LDH levels ≥2.4xUNL and age ≤36 years showed a trend to shorter PFS. Multivariate analysis showed that only the retroperitoneal metastases ≥16 cm was significant independent prognostic factor for OS (p=0.04, HR 3.86; 95% CI, 1.03-14.41) and PFS (p=0.05, HR 3.17; 95% CI, 0.99-10.15). Age ≤36 years (p=0.03, HR 4.29; 95% CI, 1.12-16.34) was also an independent prognostic factor for PFS. Conclusions: The presence of a retroperitoneal metastases ≥16 cm, a testicular tumor ≥5.5cm and age ≤36 years are associated with decreased OS and/or PFS in patients who achieved a complete response to first line cisplatin based chemotherapy. The use of these factors may assist the elaboration and implementation of new prognostic models that can guide the follow-up and management of patients with advanced testicular seminomas.

21140 Background: This study was designed to evaluate breast cancer care (BCC) in LAC trough a survey of 65 questions. Methods: We surveyed 96 opinion leaders (OL) from 12 countries that were first contacted by a researcher explaining the project and methodology. A phone interview was done by a specialist in epidemiology surveys. Answers were analyzed by center or country with Intercooled State 8 software (State Corp.) Results: 92 % OL confirm that there is no country law or guidelines making mandatory mammographyc screening. Nearly 75% of the OL stated that some type of cancer registry was available. The first consultation is done by gynecologists or breast cancer surgeons (83%), clinicians (13%) and surgeons (4%).Time lapsed from consultation until pathologic diagnosis was less than 3 months in 62% (country) and 91% (centers). Accessibility for hormone receptor and molecular markers is very good in specialized centers: 90% and 83% respectively but it is only available to 52% and 5% of country patients. Conservative surgery is widely accepted (87%) and 71% OL are able to perform sentinel node biopsies (centers). Systemic treatment is mainly based in Anthracyclines and Tamoxifen. The treatment coverage at centers is through medical insurance companies (53%), government (28%) and patient (19%) while 67% of country patients are government covered. Radiation treatment is mainly indicated by oncologists and 62% consider that radiotherapy centers in their countries are insufficient. There is adequate availability of morphine for 93% (centers) and 82% (countries).The choice of the chemotherapy or hormonal adjuvant treatment is free for 74% of those surveyed at their centers and in 23% is pre-established by the coverage. Majority of opinions are that all types of research are deficient. It is mainly organized in public institutions and sponsored by pharmaceutical companies (76%). Full results will be presented. Conclusions: We obtained data about the reality of BCC in the region. There is a general lack of prevention plans. Time to diagnosis and first treatment is similar to developed countries. Treatment according to stage is similar to international standards. Radiotherapy availability is poor. Based on this data a strategic plan for BCC in LAC will be developed. Supported by a grant from The Breast Cancer Research Foundation No significant financial relationships to disclose.

9081 Background: Osteosarcoma is a malignant tumor of the bone arising from osteoblastic cells, being more frequent in long bones; this cancer affects usually to teenagers. Mutations on TP53 and rb...

6726 Background: Acute lymphatic leukemia (ALL) is one of the most curable neoplasia in children, but the results in adults are poor. We evaluated the response, relapse, disease-free survival (DFS)...