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Introduction: It has been reported that overeating may be the greatest avoidable cause of cancer in nonsmokers and obesity increases postmenopausal breast cancer (BC) risk. Calorie restriction reduces BC incidence in experimental animals, but the evidence in humans is more limited. This study analyzes the association between female BC risk and excessive or restricted calorie consumption in Spain. Methods: EpiGEICAM is a multicenter case-control study including 1017 matched pairs (age & town) of incident BC cases and healthy controls in 14 regions in Spain. Participants filled a structured questionnaire. Average calorie intake (cals) during the 5 years previous to diagnosis (cases) or interview (controls) was estimated using a validated 117-item semiquantitative food-frequency questionnaire. Expected calorie intake (cals_exp) was calculated from a linear regression model taking into account the basal metabolic rate (Sabounchi's meta-regression) and the amount of physical activity performed by each woman (5 categories). For each woman the prediction interval (99%) of cals_exp was used to consider her calorie intake as “normal” (NCI) (cals inside this interval –the reference group-), “excesive” (ECI) (cals>upper limit of the interval) or “restricted” (RCI) (cals Results: After excluding participants with extreme calorie intake, 973 case-control pairs were considered. Average number of calories was higher in BC cases (1990 kcals) than controls (1897 kcals) P=0.001). Women with RCI (cals40% of the predicted limit) showed increased BC risk (OR=1.92; P=0.001), being this effect stronger in postmenopausal women (OR=2.81; Pheterogenity=0.001). By pathologic subtypes, no statistically significant differences were observed, but ECI (over 40%) was strongly associated with HER2+ tumors (OR=2.05, P=0.021). No differences in the effect of ECI or RCI were observed by levels of BMI, tobacco or HRT. Conclusion: After taking BMI into account, excessive energy intake increases BC risk, while relative caloric restriction seems to have a protective effect. Moderate calorie restriction, in combination with regular physical activity, could be a good strategy for BC prevention. Funding:Scientific Foundation of the Spanish Association Against Cancer (AECC), SEOM, FECMA, Cerveza y Salud Foundation, FIS CD110/00018 Citation Format: Pollán M, Castelló A, Martín M, Ruiz A, Casas AM, Baena JM, Antolin S, Ramos M, Garcia-Saénz JA, Muñoz M, Lluch A, de Juan A, Jara C, Sánchez Rovira P, Antón A, Chacón JI, Arcusa A, Jimeno MA, Bezares S, Carrasco E, Pérez-Gómez B, Lope V. Overeating and breast cancer risk by pathologic subtypes: EpiGEICAM study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-09-08.

This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ae 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

Background: Triple negative breast cancers (TNBC) have a greater risk of relapse than non-TNBC. New therapeutic approaches are needed for these patients (pts). CIBOMA/2004-01_GEICAM/2003-11 is a multinational, randomized phase III trial exploring adjuvant capecitabine (X) after completion of standard treatment in early TNBC pts. Materials and Methods: Patients with operable, node-positive (or node-negative with tumor size ≥ 1 cm), centrally confirmed hormone receptor-negative, HER2-negative early BC, who had received 6–8 cycles (cy) of standard anthracycline and/or taxane-containing chemotherapy or 4 cy of doxorubicin-cyclophosphamide (for node-negative disease) in the (neo)adjuvant setting, were eligible. Patients were randomized to either 8 cy of X (1,000 mg/m2 bid, days 1–14, every 3 weeks) or observation. Stratification factors included center, prior taxane-based therapy, number of involved axillary lymph nodes and phenotype (basal vs non-basal, according to cytokeratins 5/6 and/or EGFR positivity). The primary objective was to compare the disease-free survival (DFS) between both treatment arms, and secondary objectives included the comparison in terms of 5-year DFS, overall survival (OS) and safety. Assuming a 30% risk reduction in DFS rate at 5 years (from 64.7% to 73.7%, hazard ratio 0.70) with 80% power and a two-tailed log-rank test at 0.05, 834 evaluable pts were needed. 876 pts had to be finally enrolled considering a drop-out rate of 5%. Results: Recruitment of 876 pts from 8 countries was completed in September 2011. Median age was 49 years; 68.5% of pts were postmenopausal, 55.5% were lymph node negative, 71.7% had a basal phenotype, 67.5% received chemotherapy based on anthracyclines and taxanes. Median follow-up was 7.3 years (range 0.0 to 11.1). DFS was not significantly prolonged with X vs observation (hazard ratio (HR) 0.82; 95% confidence interval (CI), 0.63 to 1.06; P=0.1353). Five-year DFS was 79.6% (95% CI, 75.8% to 83.4%) with X and 76.8% (95% CI, 72.7% to 80.9%) with observation. OS was not statistically different between treatment arms (HR 0.92; 95% CI, 0.66 to 1.28; P=0.6228). In subgroup analysis for DFS, we found no statistically significant interaction between X treatment and different subgroups, with the exception of basal vs non-basal phenotypes (basal HR 0.97, 95% CI 0.72 to 1.32, P=0.8620; non-basal HR 0.51, 95% CI, 0.31 to 0.86, P=0.0101; interaction P=0.0357). Similar results were found for OS (basal HR 1.20, 95% CI 0.81 to 1.77, P=0.3684; non-basal HR 0.48, 95% CI, 0.26 to 0.91, P=0.0205; interaction P=0.0155). 75.2% of pts completed 8 cy of X, with a median relative dose intensity of 86.3%. Grade (G) 3 or higher adverse events (AEs) were observed in 40.4% of pts in X arm. In 9.6% of pts the AEs were related with X. Hand-foot syndrome was the most common AE in X arm (G3 on 18.8% of pts). Conclusions: In our study, the addition of adjuvant X after standard (neo) adjuvant anthracycline and/or taxane-containing chemotherapy was not associated with a statistically significant improvement of DFS or OS compared to observation in pts with early TNBC. However, in a subgroup analysis a significant DFS and OS improvement was observed with X in pts with non-basal phenotype. Sponsor: CIBOMA. Citation Format: Martín M, Barrios CH, Torrecillas L, Ruiz-Borrego M, Bines J, Segalla J, Ruiz A, García-Sáenz JA, Torres R, de la Haba J, García E, Gómez HL, Llombart A, Rodríguez de la Borbolla M, Baena JM, Barnadas A, Calvo L, Pérez-Michel L, Ramos M, Castellanos J, Rodríguez-Lescure A, Cárdenas J, Vinholes J, Martínez de Dueñas E, Godes MJ, Seguí MA, Antón A, López-Álvarez P, Moncayo J, Amorim G, Villar E, Reyes S, Sampaio C, Cardemil B, Escudero MJ, Bezares S, Carrasco E, Lluch A. Efficacy results from CIBOMA/2004-01_GEICAM/2003-11 study: A randomized phase III trial assessing adjuvant capecitabine after standard chemotherapy for patients with early triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-04.

A sentence under 'Results' heading in the Abstract section was published incorrectly. The correct sentence should read as follows.

Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited.AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg, gemcitabine 2,000 mg/m(2) plus paclitaxel 150 mg/m(2), on days 1 and 15 of each 28-day course in previously untreated HER-2 negative patients.Median progression-free survival (PES): 12.3 months. The overall response and clinical benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9-82.0 %) and 89 % (95 % CI 80.3-95.3 %), respectively. Median overall survival: 27.4 mo. Baseline circulating tumor cell (CTCs) ≥2 versus CTCs 2 was associated with lower PFS, p = 0.046. Overall response was significantly greater in patients with intense angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse events of interest with bevacizumab included bleeding (1 %) and hypertension (4 %). One patient developed cardiac ischemia (1 %).Adding bevacizumab to chemotherapy appeared feasible and well tolerated, producing toxicity comparable to other effective combined first-line regimens. Baseline circulating endothelial cells and AGTR1 expression are predictive of PFS and response.

Background-The usefulness of cardiovascular disease (CVD) predictive equations in different populations is debatable. We assessed the efficacy of the Framingham-REGICOR scale, validated for the Spanish population, to identify future CVD in participants, who were predefined as being at high-risk in the PREvención con DIeta MEDiterránea (PREDIMED) study-a nutrition-intervention primary prevention trial-and the impact of adherence to the Mediterranean diet on CVD across risk categories. Methods and Results-In a post hoc analysis, we assessed the CVD predictive value of baseline estimated risk in 5966 PREDIMED participants (aged 55-74 years, 57% women; 48% with type 2 diabetes mellitus). Major CVD events, the primary PREDIMED end point, were an aggregate of myocardial infarction, stroke, and cardiovascular death. Multivariate-adjusted Cox regression was used to calculate hazard ratios for major CVD events and effect modification from the Mediterranean diet intervention across risk strata (low, moderate, high, very high). The Framingham-REGICOR classification of PREDIMED participants was 25.1% low risk, 44.5% moderate risk, and 30.4% high or very high risk. During 6-year follow-up, 188 major CVD events occurred. Hazard ratios for major CVD events increased in parallel with estimated risk (2.68, 4.24, and 6.60 for moderate, high, and very high risk), particularly in men (7.60, 13.16, and 15.85, respectively, versus 2.16, 2.28, and 3.51, respectively, in women). Yet among those with low or moderate risk, 32.2% and 74.3% of major CVD events occurred in men and women, respectively. Mediterranean diet adherence was associated with CVD risk reduction regardless of risk strata (P > 0.4 for interaction). Conclusions-Incident CVD increased in parallel with estimated risk in the PREDIMED cohort, but most events occurred in non- high-risk categories, particularly in women. Until predictive tools are improved, promotion of the Mediterranean diet might be useful to reduce CVD independent of baseline risk., This study was funded in part by Instituto de Salud Carlos III (ISCIII) (Spanish Ministry of Economy) through grants RTIC G03/140, RTIC RD 06/0045, Centro Nacional de Investigaciones Cardiovasculares CNIC 06/2007, ISCIII FIS PS09/01292, the Spanish Ministry of Science and Innovation (MICINN) AGL2010‐22319‐C03‐02 and AGL2009‐13906‐C02‐02, and an unrestricted grant from the California Walnut Commission

Background The combination of bevacizumab (B) with taxanes, capecitabine or anthracyclines has shown increased PFS in pts with mBC. The combination with G and P has been evaluated and has demonstrated high response rate and good toxicity profile. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of B with G and P, providing an update of PFS and the toxicity experienced in all patients treated. Methods A phase II multicenter, national, open-label study in pts diagnosed of recurrent or metastatic HER-2 negative BC, treated with first line B 10 mg/kg, P 150 mg/m2 and G 2000 mg/m2 day 1 and 15 c/28 d until progression disease, unacceptable toxicity or medical decision. This abstract evaluates efficacy by PFS as primary endpoint and as secondary endpoints: response rate and toxicity profile (NCI CTC v3.0 criteria). Results From January 2009 to December 2009, 82 evaluable patients were recruited in 23 sites. The characteristic of the all of patients included (90) are: median age 51.5 (26-81), ER + 68%, PR + 59%, triple negative pts 19%, previous chemotherapy (neoadj or adj) 64.4% and ≥ 3 metastatic sites 21% of patients (19). The median cycles administered per pts was 7 (1-26) and the relative median dose intensity was 0.93 for B, 0.89 for P and 0.91 for G. Of the 75 patients with response assessment, the overall response rate obtained was 72% with a clinical benefit of 89.3% (80.6−95.28%) (CR 14.7% (11), PR 57.3% (43), SD 17.3% and PD 10.7%). Of the 82 patients with a median follow up of 16.5 m (0.16- 26.38), preliminary median PFS (43% events) for these pts was 11.48 m (8.98−15.72), the median duration of first response (MDR) was 12.4 m (7.47-NA) and the median OS was 21.35 m (20.72- NA). The one year OS% was 84.15% (74.27 - 90.47). Toxicity was generally manageable. Related AEs have been reported in 67/82 patients which were mostly mild or moderate. Safety analysis revealed 24 SAEs in 21 patients. Conclusions Bevacizumab in combination with paclitaxel and gemcitabine showed significant PFS compared with the published data with paclitaxel and gemcitabine and high clinical benefit with manageable safety profile. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-14-03.

Background: The combination of bevacizumab with taxanes, capecitabine or anthracyclines has shown increased progression-free survival in patients with metastatic breast carcinoma. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of bevacizumab with gemcitabine and paclitaxel, providing a preliminary analysis of response in patients included for whom at least one response assessment and the toxicity experienced in all patients treated. Methods: A Phase II multicenter, national, open-label study in patients diagnosed of recurrent or metastatic HER-2 negative breast carcinoma, treated with first-line bevacizumab 10 mg/kg, paclitaxel 150 mg/m2 and gemcitabine 2000 mg/m2 day 1 and 15 c/28d until disease progression, unacceptable toxicity, or medical decision. This abstract evaluates efficacy by the response rate and the toxicity profile of the combination in all cycles of all patients included. The primary end-point of the study is PFS. Toxicity is evaluated according to NCI CTC v 3.0 criteria. Results: From January 2009 to December 2009, 82 evaluable patients were recruited in 23 sites, with at least one response assessment available in 69. Median age 51.5 (26-81), ER+ 59 pts, PR+ 51 pts, triple negative patients 16 and previous chemotherapy (neoadj or adj) 58 pts. Of the 69 pts with response assessment, the last assessment is in cycle 3 for 31.88% of patients, cycle 6: 33.33%, cycle 9: 4.35%, cycle 12: 1.45% and at the end of treatment 29%. The median cycles administered per patient is 6 (1-14) and the relative median dose intensity is 0.93 for bevacizumab, 0.91 for paclitaxel, and 0.93 for gemcitabine. The overall response obtained was 69.57%, with a clinical benefit of 89.86% (CR 8.7% (6), PR 60.87% (42), SD 20.29%, and DP 10.14%). Of the 82 patients with a median follow-up of 7.19 m (0.16-13.98), grade 3-4 toxicity affected 41%, with treatment discontinuation for adverse events in 19.51%. Eighteen SAEs were reported: pyrexia (4), infection at catheter site (2), urine infection and a single case of angor, hypertension, pulmonary embolism, pleural effusion, febrile neutropenia, neutropenia, vomiting, diarrhoea, dehydration, atrial fibrillation, and dizziness. Toxicity was generally easily controlled. Conclusions: Although data from the primary study endpoint (PFS) are not yet available, the treatment regimen obtained a high overall response in patients treated and was well tolerated by this patient group. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-13.

This study was designed to evaluate the antitumor activity and tolerance of biweekly docetaxel plus vinorelbine as first-line chemotherapy in patients with metastatic breast cancer (MBC). Forty-one patients with measurable disease and no prior chemotherapy for MBC were treated with docetaxel 60 mg/m 2 plus vinorelbine 30 mg/m 2 on day 1, every 2 weeks for a maximum of 12 courses. Median age was 58 years (range, 23-75). Fourteen patients (34.1%) were premenopausal and 27 (65.9%) were postmenopausal. Most patients had received prior neoadjuvant/adjuvant chemotherapy (n = 27, 65.9%), radiation therapy (n = 22, 53.6%), and hormone therapy (n = 21, 51.2%). The most frequent sites of metastasis were bone (n = 18, 43.9%), pleuropulmonary (n = 16, 39%), and liver (n = 14, 34.1%). Twenty-seven patients (65.9%) had more than one site of metastasis. Three hundred and thirty-nine courses were given (median, 8 courses per patient; range, 1–12). Median relative dose intensity was 85% for both docetaxel and vinorelbine. Grade 3/4 toxicities included neutropenia (14 patients, 34.1%), febrile neutropenia (n = 14, 34.1%), and stomatitis (n = 4, 9.8%). No treatment-related deaths were reported. All patients were assessed for response in an intent-to-treat analysis. Four patients (9.8%) had a complete response and 19 (46.3%) had a partial response (overall response rate, 56.1%; 95% CI, 42%–70%). Six patients (14.6%) had stable disease and 12 patients (29.3%) had progressive disease. With a median follow-up of 15.1 months or until death, median duration of response is 12.6 months. Median time to progression is 12.4 months. Median survival time is 19.6 months. This biweekly combination of docetaxel plus vinorelbine is feasible and active as first-line chemotherapy in patients with MBC. This regimen is safe and well tolerated.

The development of a fully-automated portable LIPS instrument is described. The system integrates a 50 mJ per pulse Nd:YAG laser operating at 1064 nm, a 1/8 m spectrograph, an iCCD detector with computer controlled instrument operation, data acquisition and processing. A hand-held probe specially designed to provide sampling stability and ease of handling in field operations contains the laser head and the focusing and collection optics. Plasma light is guided to the main unit via a fiber optic cable. Results obtained in the field for steel scrap sorting are discussed regarding the analytical precision, accuracy, speed of analysis and sample variability. Additionally, the results are compared to those obtained by XRF at the laboratory, showing good correlation.

a ´´ Acerinox S.A, E-11379 Los Barrios (Cadiz), Spain b ´ Abstract An experimental line imaging arrangement for surface characterization of solid samples in air at atmospheric pressure using laser-induced plasma spectrometry (LIPS) is presented. A microline plasma was formed by focusing a Nd:YAG laser beam operating at 532 nm with a cylindrical lens on the sample surface. The spatial resolution was investigated as a function of beam focal parameters including cylindrical lens focal length, beam diameter and pulse energy. While focal length affected lateral resolution only slightly, a strong dependence of crater width on beam diameter and laser pulse energy was observed. For routine sample imaging the crater width obtained was close to 15 mm while the spatial resolution along the spectrometer slit was 17.4 mm. Compositional distribution maps of inclusion constituents (Mg, Ca, Si, Al and Ti) in stainless steel are shown. The results demonstrate the potential of microline imaging for fast analysis of large area samples and for screening purposes. 2002 Elsevier Science B.V. All rights reserved.

a ´´ Abstract Open-path laser-induced plasma spectrometry has been studied for elemental analysis at a distance of 45 m from the target. The 230-mJ pulsed radiation of a Q-switched Nd:YAG laser at 1064 nm has been used to produce a plasma on the sample and light emission has been collected under an off-axis open-path scheme. Under such conditions, the main variables influencing the signal response such as beam focal conditions, laser incidence angle and laser penetration depth have been identified and diagnosed on the basis of spectral signal-to-noise ratio considerations. The incidence angle is critical beyond 608. Crater morphology and ablation rates have been studied also. A semi-quantitative analysis of several stainless steel grades has been implemented using a pattern recognition algorithm, which allowed to discriminate successfully the samples on the basis of their variable content in alloying elements. 2002 Elsevier Science B.V. All rights reserved.

A pulsed Nd:YAG laser operating on the fourth (266 nm) and second (532 nm) harmonics has been used to generate plasmas on the target surface in air at atmo- spheric pressure. The influence of wavelength on quanti- tative analysis of 4 minor elements in stainless steel sam- ples (Si, Ti, Nb and Mo) was investigated. Stainless steel samples with different elemental concentrations were pre- pared and analyzed by laser-induced plasma spectrometry (LIPS). The effect of laser wavelength on analytical fig- ures of merit (calibration curves, correlation coefficients, linear dynamic ranges, analytical precision, and accuracy values) was found to be negligible when internal stan- dardization (an Fe line) and time-resolved laser-induced plasma are employed. For both wavelengths, the calibra- tion curves presented a good linearity and an acceptable linear dynamic range in the concentration interval investi- gated. For the four elements studied, limits of detection lower than 150 µg g -1 were achieved. To evaluate the in- fluence of wavelength on precision and accuracy, a set of fifteen high-alloyed steel samples from different stages of steelmaking process have been analyzed. Finally, the long-term stability of the analytical measurements for Mo with 532 nm wavelength has been discussed. RSD values were lower than 5.3% for the elements studied.

2 Acerinox, S.A., Palmones, Los Barrios, E-11379 CSpain A pulsed Nd:YAG laser operating on the second harmonic wavelength at 532 nm was used in this work. The influence of sample surface topography on spectral emission of laser-produced plasmas was investigated. Stainless-steel samples with different grades of surface polishing (range 0.026-4.54 mm) were prepared and analysed using LIBS. The effect of surface roughness on analytical precision was found to be dependent on laser beam energy, with optimum results for beam irradiances in the range 28-57 GW cm 2 . The

e11583 Background: The CONFIRM study showed greater efficacy of F500 as compared to F250.Based on these results a dosage change was authorized in Spain.The aim of this study is to describe the efficacy of F500 (progression free survival(PFS) and clinical benefit rate(CBR) in Spanish patients (P) with estrogen receptor (ER+) Metastatic Breast Cancer (MBC) through a retrospective data collection. Methods: After written informed consent, data collection was recorded from clinical records of P who previously had progressed on hormonal treatment and who received at any time F 500 from 1st January 2010 to 31st October 2011. Results: 102 P in 14 centers were included in the study, 93 P were evaluable.Median age was 65 (39-88). Histology: 80.6% ductal ;15% lobulillar. Hormonal receptors: ER+/ PgR+ 77.4%; ER+/PgR- 21.6 %. HER2 status was documented in 80P, 15% of them were HER2+. 45.4% were Ki67 +. Mean from diagnosis to metastatic disease:3.7 years, 19.3% of P had de novo metastatic disease. 21.5% of P had visceral metastases.82.8% of P had good PS (0-1) when F started.F received as 1st line in 7.5%, as 2nd line in 52.7% and 3rdor more in 39.8% of the P. Average cycles administered: 10(3-48). With a median follow up of 16 months (m) since F treatment (1.4-34.4), median PFS was 10.6 m[8.3-13.0]. CBR was 59.1% (12.9%CR, 12.9 PR and 33.3% SD≥ 24 weeks). Median PFS in P with or without CB was 23.3 m and 5.6 m respectively. Median PFS in P with F in 1 st line was 10.3 m, 11.6 m in 2nd line and 9 m in 3rd line or more. No significant differences in CBR were observed between P with or without visceral metastases (58.9 vs 60%). There was a trend in the CBR between HER –ve and +ve groups (64.7% vs 33.3% p = 0.0565). 1-year survival rate was 86% (77.3-92.3). Median Overall Survival was not calculated because only 20 P had died when data were analyzed. More frequent toxicities were: local injection site pain (11.8%), hot flushes (11.8%) and gastrointestinal disorders (8.6%). Conclusions: F500 in real life setting showed a PFS of 10.6 m and got CB in 2/3 of P with a good toxicity profile, in line with phase III trials. In P who achieve a CB the median PFS was almost two years. P with visceral metastases may benefit from F same as those with non visceral involvement.

e11535 Background: The combination of bevacizumab (B) with taxanes, capecitabine or anthracyclines has shown increased PFS in pts with mBC. The combination with G and P has been evaluated and has demonstrated high response rate and good toxicity profile. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of B with G and P, providing the final result of PFS, update of OS and the toxicity experienced in all pts treated. Methods: A phase II multicenter, national, open-label study in pts diagnosed of recurrent or metastatic HER-2 negative BC, treated with first line B 10 mg/kg, P 150 mg/m2 and G 2000 mg/m2 day 1 and 15 c/28 d until progression disease, unacceptable toxicity or medical decision. This abstract evaluates efficacy by PFS as primary endpoint and as secondary endpoints: OS, response rate and toxicity profile (NCI CTC v3.0 criteria). Results: From January 2009 to December 2009, 82 evaluable pts were recruited in 23 sites. The characteristic of the all of pts included (90) are: median age 51.5 (26-81), ER + 68%, PR + 59%, triple negative pts 19%, previous chemotherapy (neoadj or adj) 64.4% and > 3 metastatic sites 21% of patients (19). The median cycles administered per pts was 7 (1-28) and the relative median dose intensity was 0.93 for B, 0.89 for P and 0.91 for G. Of the 76 pts with response assessment, the overall response rate obtained was 72% with a clinical benefit of 89.5% (80.3-95.34%). Of the 82 pts with a median follow up of 20.21m (0.23- 30.07), median PFS (50% events) for these pts was 11.51 m (9.01-17.6), the median duration of first response (MDR) was 12.4 m (7.6-15.2) and the median OS (42% events) was 27.4 m (21.9- NA). The one year OS % was 84.15 (74.27 – 90.47). Toxicity was generally manageable. Related AEs have been reported in 69/82 pts which were mostly mild or moderate. Safety analysis revealed 24 SAEs in 21 pts Conclusions: Bevacizumab in combination with paclitaxel and gemcitabine showed significant OS compared with the published data with paclitaxel and gemcitabine and high clinical benefit with manageable safety profile.

e21088 Background: CTCs in peripheral blood are an ideal source for the detection of tumor dissemination. Their prognosis significance has been demonstrated in metastasic breast carcinoma (Cristofanilli, NEJM 2004). Beacizumab in combination with CT, improves progression free survival (PFS) of first line treatments, may modify CTC and CEC levels. Aims of this study are the evaluation of the prevalence and kinetics of CTCs and CECs before and after treatment with B in pts with MBC Methods: Pts received B 10mg/kg/q2w combined with P 150mg/m2 and G 2000mg/m2 d1,15/q28d therapy until disease progression, unacceptable toxicity or withdrawal. CTC/CEC were measured in 7.5ml of blood at baseline and after the 1st cycle of treatment. Enumeration was performed by CellSearch System, Veridex Results: Data were available for 37 pts. Median of f-up was 16.2 m. The media of CTCs was 41 cells (min0-max845) in the 1st determination and 5 cells (min0-max99) in 2nd determination. Baseline CTCs>2 was associated with statistic lower PFS 10.8 m (95%CI:7.66-16.91) compared to those with CTCs10 vs CTCs200 was associated with lower PFS 8.2m (95%CI:0.6-10.8) compared to those with 5 was associated with a median PFS of 15.2 m (95%CI:7.6-16.9) Conclusions: Our study suggests significant correlations between levels of baseline CTCs and CECs and poor prognosis. Addiction of B to 1st-line CT was related with high reduction of CECs and CTCs count.

10608 Background: Angiotensin type 1 receptor (AGTR1) is a membrane receptor implicated in the regulation of arterial pressure. It has also been related to carcinogenesis and tumor spread, and participates in neoangiogenesis. AGTR1 is expressed in a number of neoplasms as BC. In a previous neoadjuvant study, a significant relationship was observed between AGTR1 expression and CR to a regimen of chemo and bevacizumab (B). To study and confirm the relationship between tumor expression of AGTR1 and response to a regimen of chemo and B in pts with mBC. Methods: AGTR1 expression was subjected to immunofluorescence (monoclonal AGTR1 sc1173 antibody, Santa Cruz Biotechnology, CA, USA Dilution 1:50) in 50 samples of mBC pts from the AVALUZ study treated with first line bevacizumab 10 mg/kg, paclitaxel 150 mg/m2 and gemcitabine 2000 mg/m2 d 1 and 15 c/28 d until PD, unacceptable toxicity or medical decision. Immunoreactivity was reported as negative (0), low positive (1+) and high positive (2+). RNA was extracted from paraffin blocks, using the QIAamp DNA FFPE Tissue Kit and Deparaffinization Solution (QIAGEN) and expression of AGTR1 candidate gene was quantified using reverse transcription-PCR (RT-PCR). Results: 60% of the samples expressed AGTR1 (26% weak and 34% intense) – expression being more frequent in HR + tumors (65% vs 45%). Among the 50 samples analyzed, measurable disease was present in 39 pts. Treatment activity was significantly greater in the tumors AGTR1 expression 2+ (p=0.009) (Table). With a median follow-up of 19.30 months, the progression-free interval was longer in the tumors with intense AGTR1 expression (17.7 vs 10.8 months, p=0.132). More consolidated PFS and OS will be presented. Conclusions: AGTR1 expression may be useful as a predictor of response to chemo and bevacizumab. Prospective studies are needed to confirm these findings. [Table: see text]

Circulating endothelial cells (CECs) are shed from vessels and enter the circulation reflecting endothelial damage. Increased numbers of CECs have been documented in cancer, and appear to correlate with progression of the tumor. Bevacizumab (B) in combination with CT improves progression-free survival (PFS) of first-line treatments and may modify tumor cell intravasation and CEC/CTC levels.

630 Background: Zoledronic acid (ZA), a highly potent bisphosphonate, has been shown to reduce/delay skeletal-related events (SREs) in patients (pts) with bone metastatic disease, and extending tim...

1022 Background: Appropriate determination of immunohistochemistry (IHC) to define EBC subtypes is crucial for an adequate treatment recommendation. A number of studies have raised questions about the reproducibility of IHC results when comparing local and central laboratories. In this report we explore the differences between local and central determinations of TNBC status in a multinational randomized phase III trial that focuses on adjuvant C maintenance after conventional induction CT in early TNBC: CIBOMA/2004−01/GEICAM/2003−11. Methods: A total of 1.441 specimens of pts locally defined as TNBC were registered and sent to Spain for central laboratory confirmation of negative results for both Estrogen (ER) and Progesterone Receptors (PR) by IHC (

1112 Background: The combination of bevacizumab (B) with taxanes, capecitabine or anthracyclines has shown increased PFS in pts with mBC. The combination with G and P has been evaluated and has dem...

Background: Circulating epithelial tumor cells (CTCs) in peripheral blood are an ideal source for the detection of disseminated tumor cells of an easy sampling procedure. Their prognosis significance has been demonstrated in metastasic breast carcinoma and have potencial to influence the clinical management for pts. with breast cancer (Cristofanilli, NEJM 2004). The antiangiogenic agent bevacizumab (Bev.), in combination with CT, improves progression free survival (PFS) of first line treatments, may modify tumor cell intravasation and CTC count, and may change CEC levels. Aims of this study are the evaluation of the prevalence and kinetics of CTCs and CECs before and after antiangiogenic treatment with Bev in pts with metastatic breast cancer. Methods: Eligible pts. received Bev (10mg/kg q2w) combined with paclitaxel 150 mg/m2 and gemcitabine 2000mg/m2 d 1 y 15 q28d as first line therapy, until disease progression, unacceptable toxicity or withdrawal. For pts. participating in the sub-study, CTC and CEC were measured in 7.5ml of blood at baseline and after the first cycle of treatment. Samples were subjected to imnumomagnetic enrichment with an anti-EpCAM antibody and fluorescence labelled. CTCs were defined as nucleated cells (DAPI+) expressing cytokeratin 8, 18 and 19 but CD45 negative phenotype. CECs were defined as nuclear cells (DAPI+) expressing CD105 PE and CD45 negative phenotype. A sample was considered positive when 1 or more cells were detected. Results: Data are available for 37 pts. We found ≥1 CTCs before first cycle of treatment with bev in 73% of the patients (N=27). After first treatment, reduction of CTCs was found in 57% of the patients (N=16). The median number of CTCs was 34 cells/7.5 ml (min 0-max 845) of blood in the first determination and 4.79 cells/7.5 ml (min 0-max 99) in the second determination, p=0.0075. In 38% of the pts (N=14) we found ≥5 baseline CTCs and after treatment Conclusions: The addiction of bev to 1st line CT was related with high reduction of the value of baseline CTCs and CECs count, statistically significant correlation. Reduction to < 5 CTCs of patients with baseline ≥5 CTCs (unfavourable prognosis) was observed in 70% of patients. The results of this explorative study are preliminary and a large number of pts and follow-up is required. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-11.

1001 Background: Chemotherapy for patients with metastatic breast cancer is not curative. Anthracyclines and taxanes are among the most active drugs. Optimal duration of chemotherapy in women with metastatic breast cancer is an open issue. Should they receive chemotherapy to progression or should chemotherapy be stopped after a fixed number of courses? The excellent safety profile of weekly paclitaxel prompted us to evaluate its role as maintenance treatment in this setting. The primary objective was to determine if addition of maintenance weekly paclitaxel prolongs progression-free survival in women with metastatic breast cancer on first-line chemotherapy. Secondary objectives included overall survival and toxicity. Methods: Following Ethical Committee approval and informed consent, from 2002 to 2006 180 women with metastatic breast cancer and no prior chemotherapy for metastatic disease were randomized 1:1 in the TASMAN phase III trial to: 3 courses of epirubicin 100 mg/m2 day 1 q 21 days, followed by 3 courses of paclitaxel 225 mg/m2 day 1 q 21 days, without further chemotherapy or hormonal therapy until progression (arm A), or 3 courses of epirubicin followed by 3 courses of paclitaxel and then maintenance with paclitaxel 60 mg/m2 day 1 q 7 days until progression or unacceptable toxicity (arm B). Results: Median age: 51 years (range: 30–73). Median performance status (ECOG): 0 (0–2). Sites of metastases: bone (36%), liver (20%), pleura and/or lung (19%), skin and/or lymph nodes (18%). No grade 3–4 toxicities were seen with maintenance chemotherapy. As of January 1, 2009, 18 patients remained progression-free and 48 were alive, with a minimum follow-up of 2 years. Median progression-free survival was 8 months for arm A versus 12 months for arm B (p = 0.1, logrank). Median overall survival was 24 months for each arm (p = 0.7). Conclusions: Maintenance chemotherapy with weekly paclitaxel following first-line chemotherapy with anthracycline and taxane is well tolerated but does not significantly increase progression-free survival. No significant financial relationships to disclose.

801 Background: Docetaxel (D) has been concomitantly administered with capecitabine (C) offering clinical benefit to women with metastatic breast cancer (MBC) (ORR: 42%). The aim of this trial was to evaluate the efficacy and tolerance of sequentially administered D plus C as first line treatment in MBC. Methods: Patients ≥ 18 years old with MBC, ECOG performance status (PS) ≤2, HER-2 neu negative, non-chemotherapy naive were included in this prospective, multicentre, non-randomized, phase II study. Three cycles of D (100 mg/m2 d 1) followed by three cycles of C (1250 mg/m2 PO bid d 1–14), were both administered every 3 weeks. Results: To date, 18 patients are evaluable for toxicity and 12 for response. Median age 55 years (36–76); PS 0/1: 59%/41%. All patients had previously received neo/adjuvant anthracyclines treatment, 5 of them concomitant with paclitaxel. The most frequent metastatic sites were: nodes 44%, lung 28% and liver 22%. 72% patients had ≥2 metastatic sites. To date, 18 and 12 patients have...

A pulsed Nd : YAG laser was used to generate a plasma from stainless steel targets in air at atmospheric pressure. Laser focusing was found to be an important factor in the ablation process. The influence of focal conditions on spatial profiles of plasma, emission intensity and averaged ablation rate (AAR, μm pulse -1 ) of stainless steel samples as a function of laser energy are discussed. At high energies and depending on laser beam focusing, ablation efficiency tends to decrease compared to that at lower energies. This effect can be due to plasma shielding and air breakdown. The averaged ablation rate was found to be dependent on the thickness of the sample. This effect results in shielding of the incoming laser beam and redeposition of removed mate- rial in the crater. By focusing the beam inside the material free expansion of plasma is allowed, resulting in more effi- cient erosion of the sample at larger energies. For compara- tive purposes, data on ablated mass per pulse are presented.