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5508 Background: First line carboplatin(C)-paclitaxel(P) and Bev has proved to be an active combination after primary debulking surgery and improve overall survival in sub-optimal resected advanced EOC patients (pts). However, the role of Bev in the NA setting has not been well defined yet. Methods: We performed a phase II randomized open label multicentric study in pts with high grade serous or endometrioid EOC, FIGO stage III-IV, ECOG 0-2, considered unresectable in whom NA CT and interval debulking surgery (IDS) were planned. Main exclusion criteria were intestinal occlusion and contraindication for Bev. Pts were randomized to 4 courses of triweekly C AUC 6 and P 175 mg/m2 iv alone or with at least 3 courses of Bev 15 mg/kg i.v. every 3w in experimental arm. The primary endpoint was complete macroscopic response (CMR) rate at IDS. Secondary objectives were safety, surgical feasibility, optimal surgery rate (OSR), RECIST 1.1 and CA-125 GCIG response rate. Sample collection for translational research was taken at diagnosis and IDS. After surgery pts in both arms completed 3 additional cycles of CT and Bev, followed by maintenance Bev up to 15 mo. Results: Sixty-eight out of seventy-one evaluable pts. Clinical pts characteristics were well balanced, median age 60.0 y.o and a 33.8% stage IV. No differences in CMR were found at IDS (2/33 Control and 2/35 Bev). Bev arm was favoured in rate of surgical feasibility (66.7 vs 88.6%, p = 0.029), while no differences were found in OSR (63.6 vs 65.7%, p = 0.858) and in number of pts considered unresectable at time of IDS (2 vs 0). Median time from IDS to restarting Bev was 7.1 w. Median PFS was 20.3 mo in both arms, 20.13 mo in control arm and 20.36 mo in Bev arm, HR: 1.14 (IC 95%, 0.656 - 1.994). There were lower rates of serious adverse events (grade 3-4) in Bev arm (69.7 vs 42.9%, p = 0.026). 8 pts presented AE of special interest in Bev arm (3G2 proteinuria, 1G2/1G3 hypertension, 1G3 entero-vaginal fistulae, 1G3 entero-cutaneous fistulae, 1G3 deep venous thrombosis, 1G2 bleeding, 1G1 surgical dehiscence). Conclusions: NACT with Bevacizumab was feasible and improved the surgical outcomes at IDS in pts initially considered unresectable. Clinical trial information: 2012-003883-31.

1036Background: Obesity is not clearly associated with toxicity of chemotherapy, and ASCO’s guidelines recommend full-weight based dosing. Appropriate consideration of comorbidity is also especiall...

5554 Background: Early stage ovarian cancer (ESOC) represents 10-15% of all Ovarian Cancer (OC) cases and most frequent ESOC substage (IC) has undergone major changes in FIGO 2014 staging. Methods:...

5528 Background: Treatment with the trifunctional anti-EpCAM x anti-CD3 antibody, Catumaxomab, has shown antitumor activity in patients with advanced OC and refractory ascites. We explored prospectively the potential activity of C as consolidation therapy in pts with clinical complete response (CCR) following treatment for relapse. Methods: Pts with 2nd or 3rd CCR (CA-125 14 m would be considered clinically mea...

5558 Background: Granulosa-cell tumors (GCTs) of the ovary are a rare entity characterized by its genomic stability, presenting a punctual mutation at the FOXL2 gene, 402C→G (C134W), in the vast ma...

5582 Background: Early stage ovarian cancer (ESOC) represents 10-15% of all Ovarian Cancer (OC) cases and the reported experience is limited. Methods: A centralized prospective register of ESOC (I-...

585 Background: The association of tumor microenvironment immune response with outcome after breast cancer (BC) NCT has been suggested by several studies. However, the relevance of each TIL subpopulation is still controversial. The objective of this study was to evaluate the predictive and prognostic value of TIL before and after NCT in patients with BC. Methods: We analyzed TIL and CD68 cells in pre- and post-chemotherapy biopsies of BC patients treated with NCT (80.4% sequential AC-docetaxel). A tissue microarray with paired pre- and post-NCT biopsies was built, and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD20, FOXP3 and CD68. Morphometric analysis (TIL count/mm2) was performed after slide scanning and digitalization. Results: We included 121 consecutive patients with invasive BC, most of them with stages IIB (28%) or IIIA-C (56.4%). IHC phenotype: 50.4% Her2- hormone-sensitive (HS), 13.2% Her2+ HS, 10.7% Her2+ non-HS, and 21.5% triple negative. Pathologic complete response (pCR): 17.4%. Median overall survival (OS) and disease free survival (DFS) has not been reached (median follow-up: 60 months). Higher than median pre-NCT TIL infiltration was predictive of pCR to NCT: CD3 > 172/mm2 (p=0.001; Hazard Ratio [HR]: 9,61, 95% confidence interval [95%CI] 2.49–37.02); CD4 > 67/mm2 (p=0.001; HR: 8.82, 95%CI 2.43–31.96); CD20 > 42/mm2 (p=0.001; HR: 8.71, 95%CI 2.31–32.74). Logistic regression multivariate models including grade and IHC phenotype confirmed the independent predictive value of higher pre-NCT CD3, CD4, and CD20 for pCR. In the group of patients with HS Her2- BC without pCR (n=44), higher infiltration (cut-point: median value) by some TIL subpopulations and by CD68 cells in post-NCT residual tumor associated to lower DFS: CD8 > 37/mm2 (log-rank; p=0.04), CD20 > 14/mm2 (p=0.07) and CD68> 39/mm2 (p=0.06). Conclusions: Higher pre-treatment CD3, CD4 and CD20 TIL predicted pRC in patients with invasive BC receiving anthracyclines and taxanes NCT, while higher infiltration of residual tumor by CD8 associated to worse DFS in patients with HS Her2- BC without pCR after NCT. TIL might be useful as predictive factors in the setting of NCT for BC [Supported by GEICAM-Beca Ana Balil].

3042 Background: Growing evidence indicates that EMP may both modulate angiogenesis and endothelial injury in cancer and cardiovascular disease. However, it has not been shown whether in vivo release of EMP might reflect the tumor response or the antiangiogenic effects of chemotherapy (CT). The aim of this work was to evaluate the relationship between the levels of small-size EMP (sEMP) and resistance to CT in locally advanced and metastatic BC. Methods: Citrated platelet-free plasma was obtained from BC patients before and after 3-4 cycles of chemotherapy. Small-size CD144+ sEMP (0.1-0.5 μm diameter) were prospectively quantified using a high resolution Apogee A50 flow cytometer. Association of EMP with clinical variables, response to CT and survival was analyzed. Response (partial or complete) was defined by RECIST criteria. Results: 45 BC patients were included (20, metastatic; 25, locally advanced). Treatment included anthracyclines in 66.7% of patients and taxanes in 15.5%. Small-size EMP baseline counts were higher in premenopausal women (p=0.008), but no association with other clinical or pathological characteristic was found. A significant decrease of circulating sEMP was observed after treatment with CT in the whole group of patients with paired samples available (n=33): pre-CT: 416.2 ± 365 vs. post-CT: 340.7 ± 458 (p=0.005). Lower chemotherapy-induced sEMP decrease was associated to treatment resistance: ROC analysis demonstrated a 66.7% sensitivity and 72.2% specificity of lower sEMP decrease for lack of response to CT using a decline cut-point of -40 sEMP (close to median decrease: -47). With the same cut-point of low sEMP decrease, odds ratio for treatment resistance was 5.2 (95% confidence interval, 1.17-23.04; p=0.03). No clear association of the degree of sEMP decrease was found for disease or progression free survival in the neoadjuvant or in the metastatic setting. Conclusions: This study suggests that circulating sEMP decrease after CT and are tightly associated with treatment resistance in BC patients. These findings indicate pathophysiological roles for sEMP in BC and support their potential role as treatment resistance biomarkers.

e11024 Background: Bcl-2 expression has been related to hormonal dependence and better prognosis of breast cancer. Although some reports suggest that its expression has an independent prognostic value, especially in N positive patients, the clinical relevance of determining Bcl-2 is unclear. The aim of this work was to analyze which other tumor markers predict Bcl-2 expression in breast cancer and explore its prognostic value. Methods: Immunohistochemical expression of ER, PR, Her2-neu, Ki-67, p53, cathepsin-D and Bcl-2 was prospectively examined in a series of 87 consecutive invasive BC patients. Bcl-2 was semiquantitavely scored according to a validated system (Treré, 2007). Correlation between variables was analyzed with Chi-square test; disease free (DFS) and overall survival (OS) were analyzed by log-rank test and Cox models. Results: Patient characteristics: median age 57 yrs (31-86), 64.5% postmenopausal; treatment: 49.5% breast-preserving surgery, 71.6% adjuvant-neoadjuvant chemotherapy, 72.1% adjuvant radiotherapy ; tumor histology: 83.9% ductal invasive carcinoma, 28.2% grade 3; stage: T1:57%, T2:31.2%, T3-4:8.6%, 48.9% nodal metastasis (pN1:36.7%; pN2:12.2%); tumor phenotype: 77.2% ER+ , 78.3% PgR+ , 9.7% Her2-neu+, 50.6% high Ki-67 (>13%). Immunohistochemical evaluation for Bcl-2: 41/87 (47.1%) positive cases. No expression of Bcl-2 was observed in ER/PgR negative tumors (p< 0.001). Bcl-2 expression was associated to histological grade 1-2 (p=0.009), absence of Her2-neu amplification (p=0.03), p53+ status (p=0.008) and lower cathepsin-D expression (p

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.

e15590 Background: To evaluate the safety and efficacy of bevacizumab (BEV) alone or combined with chemotherapy (CT) in a compassive use program sponsored by the Spanish Ovarian Cancer Research Gro...

e20601 Background: Elevated D-Dimer (DD) is related with activated coagulation system. We pretended to assess if high DD is predictive of thrombosis in ambulatory cancer patients. Methods: We prospectively determined DD in plasma specimens from ambulatory cancer patients, without previous thromboembolic events (TE), before chemotherapy initiation. DD was determined with an immunological test in an automated coagulometer (IL D-Dimer test, Instrumentations laboratory). The selected cut-off point for DD was 1.5 x UNL, as it was the nearest point to the median DD. All thromboembolic events were recorded. Results: Between June 2007 and December 2008 eighty four patients were included, 66% with advanced and 34% with early disease. The most frequent tumours were colorectal 31%, breast 27% and genitourinary cancers 30% (12% HR prostate and 28% non prostate cancers). Antiangiogenic drugs were included in 24% of treatments (16% Bevacizumab and 8% Sunitinib). Median ECOG was 1. With a median follow-up of 6.5 months, 12 thromboembolic events were observed (5 PE, 3 DVT and 4 Arterial thrombosis). The following variables were included in the univariate analysis: high DD (>1.5 x UNL), low haemoglobin (Hb No significant financial relationships to disclose.

e11537 Background: There is evidence about chemotherapy creating a better tumor control by inmune system. Neoadjuvant treatment is an excellent situation to study tumor behaviour. The aim of this study is to determine whether decreases on blood lymphocytes (BL) absolute number have a prognostic significance on women with breast cancer receiving primary chemotherapy (PC). Methods: A retrospective analysis was performed of 105 breast cancer patients who underwent PC. Doxorubicin (60mg/m2q3w) - Cyclophosphamide (600mg/m2q3w) x4c followed docetaxel (100 mg/m2q3w) x4c was PC regimen in 73,4%. We collected data on BL before the first cycle of PC (basal BL), just before second doxorubicin- cyclophosphamide (AC) cycle (BLa), and three weeks from the end of PC (BLb). The median decrease (MD) in blood lymphocytes has been calculated: MDa = BLa - basal BL; MDb = BLb - basal BL. Results: Of 105 patients with breast cancer 16,2% were clinical stage IIA, 19% IIB, 30,5% IIIA, 14,3% IIIB, 15,2% IIIC. The mean age was 50 years. The complete pathologic response (pCR) rate was 14,9% in primary tumor, and 37,9% in axillary nodes. The median follow up is 25 months (mo). Overall survival: (OS) 25,3 mo (range 4 - 89.3). Disease-free survival: (DFS) 21,8 mo (range 5 - 80.3). The median decrease on blood lymphocytes is MDa=300 106/L(2400, -1000), MDb=700 106/L(3900, -400). A decrease on BL just before second AC cycle (> MDa=300 106/L) is correlated with worse DFS, in univariant and multivariant analysis (HR =4.022; 95% CI:1.105–14.63; p 0.035 at first; HR=5.36; 95% CI:1.1–25.82; p 0.037 at former). Patients with BL decrease three weeks after finishing PC (>MDb=700 106/L) have worse DFS in univariant as multivariant analysis (HR=5.9 95% CI:1.2–27.5; p0.022 at first; HR=9.7 95% CI:1.11- 85.07; p 0.04 at former). We have not found significant differences in OS. Conclusions: A decrease on blood lymphocyte number in women with breast cancer undergoing primary chemotherapy is correlated with worse DFS. No significant financial relationships to disclose.