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e13114Background: 80% of breast cancers - BC are basal; aggressive, and negative for ER, PR and HER2 over expression, termed triple negative - TNBC. In the US, the incidence rate of TNBC is two-fol...

e12028 Background: Continuous exposure of breast cancer cells to adriamycin (ADR) induces the over-expression of P-glycoprotein (P-gp) and multiple drug resistance. However, the biochemical process and underlying mechanisms are not clear. Our previous study revealed that ADR increased reactive oxygen species (ROS) generation and reduced glutathione (GSH) biosynthesis, while N-acetylcysteine, the ROS scavenger, reversed the over-expressed P-gp induced by ADR. Methods: Based on MCF-7 breast cancer cells and the adriamycin-resistant MCF-7 subline (MCF-7R), we investigated the P-gp expression on mRNA, protein and function level by qPCR, western blotting, flow cytometry and laser scanning confocal and so on, under SLC7A11 down-regulation/over-expression, cystine depletion/supplement, increased ROS generation and combined factors. Results: The present study showed that ADR inhibited cystine influx (source material of GSH) and SLC7A11 transporter (in charge of cystine uptake) in MCF-7 cells. For the first time, we showed that a down-regulation/silence of SLC7A11, or cystine deprivation, or an enhanced exposure of ROS agents directly and significantly increased P-gp expression; yet, a combination of either an inhibited/silenced SLC7A11 or cystine deprivation and an increased ROS dramatically promoted the P-gp expression in MCF-7 cells. On the contrary, an over-expression of SLC7A11, or sufficiently supplementary cystine, or scavenger of ROS significantly depressed P-gp expression and activity. Moreover, the down-regulation of SLC7A11 and cystine deprivation induced an elevation of ROS and P-gp that could be reversed by N-acetylcysteine. It was suggested that ROS and SLC7A11/cystine were the two relevant factors responsible for the upregulated expression and function of P-gp. Conclusions: This study provided the direct evidences suggesting that ROS triggered over-expression of P-gp and demonstrated that the combination of either an inhibition of SLC7A11 or cystine influx and elevated ROS was the underlying mechanism contributing to P-gp over-expression induced by ADR. It was indicated that the SLC7A11 might be a potential target modulating ADR resistance.

4526Background: FGFR3 aberrations are common in low grade non-muscle invasive bladder cancer (NMIBC) tumors but decrease in frequency in metastatic UC. This multisite single-arm trial assessed the ...

4044 Background: Epidermal growth factor receptor (EGFR) has been reported to be overexpressed in esophageal cancer, suggesting EGFR-directed treatment is a potential option. Here we report the ant...

e19507 Background: Double hit lymphoma (DHL) is recently recognized as a highly proliferative subtype of Diffuse Large Cell Lymphoma characterized by over expression of cMYC and Bcl-2 with an overa...

50th Annual Meeting of the American-Society-of-Clinical-Oncology -- MAY 30-JUN 03, 2014 -- Chicago, IL, WOS: 000358613200488, …, Amer Soc Clin Oncol

e22096 Background: The MDM2 inhibitor which disrupted the MDM2-p53 interaction made little effort on the activation of p53 for breast cancer treatments, due to MDMX over expression. Previously a small molecule inhibitor targeting at MDM2 and MDMX had been successfully synthesized. We tested anti-tumor activity of the small molecule MDM2/MDMX inhibitor, compared with nutlin-3α, a well characterized MDM2 inhibitor, in the wild-type (wt) and mutant (mt) p53 breast cancer cell lines. Methods: Human breast cancer cell lines MCF-7 (wt-p53), ZR-7530 (wt-p53), BT-474 (mt-p53) and MDA-MB-231 (mt-p53) were cultured and treated with the small molecule MDM2/MDMX inhibitor, nutlin-3α or phosphate buffer solution (PBS) for 48 hrs separately. MTT for cell viability, FCM for cell cycle arrest and Annexin V FITC/PI for cell apoptosis were performed. The mechanism of antitumor activity of the small molecule MDM2/MDMX inhibitor was determined by Western-Blot analysis. Results: The inhibitor of MDM2 and MDMX inhibited cell growth and induced cell cycle arrest and apoptosis in mt-p53 breast cancer cells while nutlin-3α cannot. In the breast cancer cells with wt-p53, both of them inhibited cell growth, induced cell cycle arrest and apoptosis, but MDM2/MDMX inhibitor was proven to be more effective. Western Blot revealed that there was higher level of p53 expression in breast cancer cells treated with MDM2/MDMX inhibitor than nutlin-3α. The marked increases in p21, Bax and PUMA expressions were abserved in both wt-p53 and mt-p53 breast cancer cells which indicated that the small molecule MDM2/MDMX inhibitor induced cell apoptosis through p21, Bax and PUMA over expressions. Conclusions: The small molecule MDM2/MDMX inhibitor would be able to suppress cell proliferation, induce cell cycle arrest and apoptosis, activate p53 more effective than nutlin-3α in breast cancer cells, no matter with p53 status. P21, Bax and PUMA were involved in the mechanism of apoptosis induction. The inhibitor of targeting at both MDM2 and MDMX will be a novel treatment for breast cancer p53-independent status in the future.

e14672 Background: There is no suggested molecular indicator in identifying which patients will benefit from anti-angiogenic treatment in metastatic colorectal cancer. Over expression of vascular endothelial growth factor (VEGF) and Hypoxia Inducible Factor 1-alpha (HIF-1α) are associated with bad prognosis. In this study, VEGF and HIF-1α expression and their clinical significance are studied in tumor tissues of patients with colorectal cancer receiving treatment with bevacizumab. Methods: VEGF and HIF-1α were observed immunohistochemically in primary tumors of 53 patients. The expressions were separated by evaluating low and high of VEGF and HIF-1α expression. We evaluated whether expression of VEGF and HIF-1α can help to predict treatment response, progression free survival (PFS), and overall survival (OS). Results: Fifty-three patients were enrolled in the study. Median age was 55. VEGF was strongly expressed in 30 patients (57%) whilst low expression was observed in 23 of them (43%). When VEGF expression was evaluated in association with therapy response rates; the clinical benefit rate was 38% in the low expression group whereas it was 62% in high expression group. This difference was statistically significant (p=0.01). In the group with strong VEGF expression PFS was 10 months whereas it was 8 months in the low expression group (p=0.009). When evaluated for OS, 26 months versus 15 months was in favor of highly expressed VEGF group (p=0.03). Highly expressed HIF-1α was found in 29 patients (55%), on the other hand low expressed HIF-1α was detected in 24 (%45) patients. For clinical benefit rates, PFS and OS there was no difference between high and low expressed HIF-1α groups. Conclusions: It has been demonstrated that VEGF and HIF-1α expressions are associated with poor prognosis in several tumors, mainly colorectal carcinomas. With the better understanding of carciogenesis and angiogenesis at molecular level, especially VEGF and HIF-1α became target molecules of the therapy. According to results of our study, VEGF expression is a predictive factor in designating the metastatic colorectal cancer treatment.

e14695 Background: In metastatic colorectal cancer treatment more successful results are achieved by adding anti-angiogenic therapy to the chemotherapy. Over expression of VEGF in colorectal cancer is known to be a poor prognosis factor but its effects on designating the therapy is not clear. In this study, results of the patients receiving FOLFIRI + Bevacizumab or XELOX + Bevacizumab were compared for VEGF expression. Methods: VEGF was assessed immunohistochemically in primary tumors of the 53 metastatic colorectal cancers. Severity and conformity of VEGF expression was evaluated. Results were used to assess the association with the therapy response, progression free survival (PFS) and overall survival (OS). Results: The median age of the patients was 55 (range, 32-79). In combination with bevacizumab 38 patients received FOLFIRI and 15 patients received XELOX. In 30 patients (57%) there was a strong expression of VEGF and in 23 patients (23%) the expression was weak. In the high VEGF expression group, PFS was 11 months in FOLFIRI receiving patients and 8 months in XELOX receiving ones but in low expression group PFS was 8 months in patients receiving either one of the two treatment protocols. In high expression group, PFS in FOLFIRI-bevacizumab combination receiving patients was different and this difference was statistically significant (p=0.009). Overall survival in FOLFIRI receiving patients with high VEGF expression was 26 months and with low VEGF expression it was 16 months (p=0.04). Median OS was not reached in the XELOX receiving patient group. FOLFIRI regime clinical benefit was 58% in high VEGF expression group whilst it was 34% in low expression group. This difference was not statistically significant but it was close to the significance threshold (p=0.06). There was no association between the therapy responses and VEGF expression of the 15 patients who received XELOX. Conclusions: There is no difference in efficacy between the first line chemotherapy regimens of the metastatic colorectal cancer. In this study, in metastatic colorectal patients with over expressed VEGF first line FOLFIRI-bevacizumab combination led to better response and survival rates.

e14081 Background: In vitro, prolonged exposure of colon cancer cells to 5-FU induces resistance and is associated with increased synthesis of thymidylate synthase (TS). 5-FU resistance is well correlated with the over expression of intratumoral TS mRNA which if down regulated may reverse 5FU resistance. Earlier we demonstrated that ATO significantly down regulated TS in vitro and in patients thereby sensitizing them back to 5-FU. Methods: A treatment cycle consisted of four weeks of therapy and one week of rest. On days one through five, 8, 11, 15 and 22, the patients (pts.) received a 4-hour ATO infusion; on days 8, 15 and 22 a 24-hour 5 FU/ leucovorin infusion. To date 12 pts with refractory metastatic colorectal carcinoma were enrolled. In the 5-FU dose escalation phase, patient one received 1,600 mg/ m2; patient two 2,000 mg/m2; patient three 2,300 mg/m2; patient four and all the subsequent patients 2,600 mg/m2 of 5-FU. ATO was infused at 0.15 mg/kg in patient one through seven and at 0.20 mg/kg in p...

14674 Background: The incidence of HER-2 over expression among Omani breast cancer patients was reported as 40% (higher than international published figures). Since 2002 a total of 76 patients with...

16029 Background: Squamous cell carcinoma of the penis (SCCP) can be an aggressive, disabling disease and a limited body of published literature exists in this area. Furthermore, standard chemother...

11518 Background: The first random study of incidence of Her-2 over expression among Omani breast cancer patients was carried out by the Medical Oncology Department, the Royal Hospital in 2001. The incidence was reported as 40% (higher than international published figures). The Herceptest was routinely performed on all new patients for a whole year (2004) and the incidence was found to be 36%. Trastuzumab was approved for use in the Sultanate of Oman in 2002, since then a total of 26 patients with metastatic breast cancer received Trastuzumab, the results are presented. Methods: Prospective, single arm, single centre experience. Patients with confirmed metastatic breast cancer (at presentation or after adjuvant treatment), HER-2 positive (+++ by Herceptest, or FISH positive), age > 18, ECOG PS ≤ 2, LVEF = 50% and adequate renal & liver function, were included. Treatment consisted of trastuzumab as single agent or in combination with chemotherapy as indicated. A loading dose of 8mg/kg was followed by 6mg/kg q3 weeks. The endpoints were response rate (RR) progression free survival (PFS) and survival (OS). Results: a total of 26 patients were included between October 2002-October 2006, median age was 45.5years (27–60), 12 patients presented with metastasis at first presentation and 14 had metastatic disease 6 months or more after finishing adjuvant chemotherapy. The median number of received cycles was 10 (range 4–30), the overall response rate was 77% (54% CR and 23% PR), the median survival 15 months (range 4–36m), median Time to Progression 9m (range 4–33m). Six patients (23%) developed brain metastasis while on herceptin. There were 8 events (disease related deaths) during the study period. Conclusions: The incidence of Her-2 +ve breast cancer in Omani patients is slightly higher than the reported figures in international studies. The response to trastuzumab in metastatic disease is comparable to other similar studies. No significant financial relationships to disclose.

1069 Background: Breast cancer mortality is similar in Norway, Spain and Sweden (14–16/100,000 Age Standardized Rate). There are only small regional differences in incidence and mortality within the countries. Trastuzumab (T) was approved for metastatic breast cancer (MBC) in Norway, Spain and Sweden in second half of year 2000. T represents a unique new treatment for MBC that delays disease progression and improves survival. HER2 over expression (H+) is used to identify patients eligible for trastuzumab treatment (T). Methods: This study use sales data from IMS Health and incidence and mortality data from regional and national cancer registries as well as data from International Agency for Research on Cancer. We examines the variation in the use of T in different health care regions of Norway (4 regions), Spain (19 regions) and Sweden (6 regions) as well as differences in use between the countries. These results were also put into a global comparison. Results: There are marked differences in both the rate and level of uptake between the countries. Three years after approval the Spanish uptake was close to 90 % and twice the Swedish and 3–4 times the Norwegian uptake. The regional variations within the countries are of the same magnitude, a factor 2–3. Based on an assumed H+ rate of 25% and a treatment time of 38 weeks we estimate the proportion of H+ MBC patients that have been treated with T during the period 2000–2005 to be 24% in Norway; 66% in Spain and 44% in Sweden. In all countries there has been an increase in the use during the second half of 2005, indicating a use also in the adjuvant situation. T was approved for adjuvant treatment of BC in Europe in April 2006. Conclusions: Access of trastuzumab to patients with MBC in Norway, Spain and Sweden has been very variable. Spanish MBC patients have had earlier access to T than Swedish patients. Norwegian patients have had the lowest access. Regional differences in the use are in the magnitude of a factor 2–3. On a global level the Spanish uptake is in line with the uptake in the USA, Switzerland and Austria; the Swedish uptake is at an average European level and the Norwegian uptake is at a low level, similar to Czech Republic, Hungary, New Zealand, Poland and the UK. No significant financial relationships to disclose.

7577 Background: JBR.10, a phase III inter-group trial randomized 482 patients with resected stage IB & II NSCLC to receive 4 cycles of adjuvant cisplatin + vinorelbine or observation alone. Chemotherapy patients had an overall survival (OS) benefit (Hazard Ratio [HR] 0.69, p=0.04). P53 has important regulatory roles in cell cycle progression, apoptosis, gene transcription and DNA repair. We evaluated the prognostic and predictive value of p53 in JBR.10. Methods: P53 protein expression was evaluated by immunohistochemistry (IHC) on tissue micro-arrays (282 available blocks). We used the DO7 antibody, and defined ≥15% nuclear staining as the cutoff for over- expression. Mutations in exons 5–9 were determined by denaturing high performance liquid chromatography (446 available samples), followed by sequencing of aberrant PCR products. Results: Successful assays: p53 mutation, 403/446 patients; p53 IHC, 254/282 patients. P53 gene mutations were found in 126/403 (31%) patients. In the observation arm, mutations were not prognostic of poorer survival (HR = 1.18, 95% CI 0.77–1.81; p= 0.45). Adjuvant chemotherapy effect was not significantly different in p53 mutated and wild type patients (interaction p = 0.66), the estimated HR was 0.68 (95% CI 0.46–1, p=0.047) for patients with wild type p53, and 0.79 (95% CI 0.47–1.33, p=0.37) for mutated patients. P53 protein over-expression was found in 133/254 (52%) patients. Patients with over-expression in the observation arm had a higher risk of death than patients with low expression (HR 1.89, 95% CI 1.07–3.34, p=0.03). However, the adjuvant chemotherapy effect was significantly better in p53 over-expressing patients (interaction p= 0.018), with an estimated HR of 0.53 (95% C.I. 0.31–0.90, p=0.03) for p53 over-expressing patients, and 1.40 (95% C.I. 0.78–2.52, p=0.26) for low expressing patients. Conclusions: P53 protein overexpression but not p53 gene mutation is both a significant prognostic marker of poorer survival in the JBR 10 population and a significant predictive marker for the benefit of adjuvant chemotherapy. [Table: see text]

14085 Background: The Gi protein associated A3 adenosine receptor (A3AR) is highly expressed in colon carcinoma tissue and is reflected in peripheral blood mononuclear cells (PBMC) of the patients. Drug candidates with high affinity to the receptor possess anti-cancer effect when administered orally to colon carcinoma bearing animals. The receptor was suggested as a potent therapeutic target and predictive biological marker. Since there is no adequate therapy for Hepatocellular Carcinoma (HCC) we looked at the presence of A3AR in tumor and PBMC of HCC patients and tested the efficacy of the A3AR agonist, CF102 in an experimental rat HCC model. Methods: mRNA and protein A3AR expression level were examined in paraffin embedded slides and PBMC from HCC patients utilizing RT-PCR and Western blot (WB) analysis, respectively. Rat HCC model was established by inoculating N1S1 cells to the animals’ liver. Oral treatment with CF102 was initiated 5 days after tumor inoculation. Signaling proteins in tumor lesions and PBMC from the animals was tested by WB analysis. Results: A3AR over-expression was found in tumor and PBMC of HCC patients. Receptor over-expression was attributed to high expression of NF-κB, known to act as a transcription factor of A3AR. In the HCC bearing rats, A3AR was over-expressed in the tumor tissue and PBMC. Upon treatment with CF102 A3AR expression was down-regulated followed by inhibition of tumor size (60%±18.4%, p3AR which is up- regulated in HCC tumors may be suggested as a new target to treat this malignancy and as a biological marker to follow up tumor response to the drug. No significant financial relationships to disclose.

15637 Background: The significance of over expression of Erb-1 (epidermal growth factor receptor/ EGFR) and Erb-2 (Her-2) has been reported in various tumors. The aim of this study was to investigate the correlation of the expression of EGFR, Her-2 and p53 with relapse free survival (RFS) and over all survival (OS) in patients with muscle invasive bladder cancer Methods: All patients with muscle invasive bladder cancer diagnosed at our institution between1993and 2004 were considered for the study. Immunohistochemical staining for EGFR, Her2 and p53 performed on formalin-fixed paraffin-embedded archival tissue was evaluated as positive or negative without knowledge of clinical outcome. Survival data determined by reviewing patients medical records were correlated with the staining results. Results: Of the 46 patients who qualified for the study, 40 had slides interpretable for Her 2 and p 53 staining and 38 had slides interpretable for EGFR staining. 35 of 38 were EGFR +ve, 22/40 were Her-2 +ve and 12/40 were p53+ve. The median age of the 46 patients was 67.5 years with a male/female ratio of 60% and 40%. 83% had clinical Stage 2; of those 42%, 23%, and 35% had pathological stages T2, T3 and T4 respectively. Six of 46 (13%), received adjuvant therapy. Tumor histology was pure transitional carcinoma in 56%, or with other components (squamous or adenocarcinoma) in 44%. Median follow-up was 48.8 months for RFS and 44.9 months for OS. Patients with positive EGFR had a median RFS of 34.8 months and median OS of 59.8 months. In patients with negative EGFR, median RFS and OS were not yet reached. Her 2 positive patients had median RFS of 19.2 months compared to 63.8 months in Her-2 negative patients. Her-2 negative patients had median OS of 59.7 months while median was not reached in Her 2 positive patients. Conclusions: While the differences are not statistically significant, the trends observed warrant prospective investigation of the prognostic significance of these markers in a larger population of muscle invasive bladder cancer patients. No significant financial relationships to disclose.

15606 Background: Mechanisms of hormone resistance for AIPC are variable. One proposed mechanism is the over expression of the epidermal growth factor receptor (EGFR) which in turn stimulates proliferation through its pathway. We aimed to determine the efficacy of an oral anti-EGFR inhibitor (erlotinib) in this patient population that was chemotherapy-naive. The primary end point was to evaluate the overall clinical benefit defined as the sum of complete response (CR), partial response (PR), and stable disease (SD). Methods: Between January and December 2006, sixteen patients were enrolled onto this phase II study. Median age was 78 years (66–85). Median PSA was 61.9 (9.2–800.2). Median time from initial diagnosis until starting Erlotinib was 7.8 years. Erlotinib was given daily at 150 mg until disease progression. Patients were evaluated every 2 weeks for toxicity. Response assessment took place every 2 cycles (each cycle was 4 weeks). Evaluations included computed tomography of measurable disease areas, bone scans, and serum PSAs. Patients who progressed radiographically but maintained a PSA response or those who progressed biochemically but maintained a radiographic response were considered stable and were allowed to continue on study. Results: Sixteen patients were enrolled with 14 being evaluable at this time (2 patients are early in their course). Median cycles received is 2 (range 1.5–12). One patient achieved a PR and continues on Erlotinib after one year of enrollment. Three patients demonstrated stable disease but two of them later progressed. One patient withdrew after 9 days of starting therapy due to fatigue and poor taste. All other patients developed disease progression after two cycles of therapy. The calculated overall clinical benefit was 28% (4 responses out of 14 patients). One patient died from pneumonia and seizures unrelated to Erlotinib as confirmed by an autopsy that showed progression in the central nervous system. Erlotinib was well-tolerated with skin rash and diarrhea being the most common toxicities. Conclusions: Erlotinib has clinical activity as a single agent in AIPC. Updated results of this ongoing study will be presented at the meeting. Further studies with this agent alone or in combination are warranted. No significant financial relationships to disclose.

20058 Background: Over expression of epidermal growth factor receptor (EGFR) has been reported as a poor prognostic factor in patients with cancer. However, active EGFR released from the apoptotic tumor cells could serve as a marker for the prediction of clinical outcome in cancer patients. In this study we aimed to study the role of the level of serum active epidermal growth factor receptor in patients with non-small cell lung cancer as a predictive parameter for response and survival. Methods: Thirty-three consecutive patients with advanced non-small cell lung cancer patients (12 with stage IIIB and 21 stage IV or relapsed disease) were included. The median age was 52 (range: 35–69). The patients were given cisplatinum and docetaxel combination regimen as first line treatment. The serum samples were collected before the first cycle of the chemotherapy and every 2 cycles and kept at -80 C. Response to treatment was evaluated every 2 cycles according to the WHO criteria. Serum active EGFR levels were measured by ELISA (BioSource, Camarillo Ca, USA). Results: Median 4 cycles of chemotherapy (range: 2–6) were administered. Median follow-up time was 11 months. Objective response rate was 18.2%. One-year estimated survival rate was 65.9%. There were no significant differences between the extend of the disease and basal active EGFR levels. Likewise, there was no difference between the basal active EGFR levels of responders and non-responders (0,19 ± 0.09 vs 0.21 ± 0,11 fmol/mL, p = 0.899, respectively). However, the patients responded to the treatment had significantly higher level of active EGFR than the non-responders after 2 cycles (3,74 ± 3,65 vs. 0,174 ± 0,13 fmol/mL, p = 0.028, respectively). While the patients with positive basal EGFR levels (higher than the cutoff level of 0.080 fmol/mL) had lower survival rates than that of negative patients (1 yr survival rate: 62.8% vs. 75%, respectively), active EGFR positive patients after 2 cycles of chemotherapy had longer survival than the negative patients (1 yr survival rate: 70.6% vs. 60%, respectively). Conclusions: Our preliminary results show that serum active EGFR levels could be a predictive marker for response evaluation and survival in patients with non-small cell lung cancer treated with chemotherapy. No significant financial relationships to disclose.

649 Background: As systemic therapy improves, brain metastases (BM) from breast cancer are becoming increasingly evident. An increased risk of BM in HER-2/neu over-expressing metastatic breast cancer patients has been suggested. However, the relationship between HER-2/neu over-expression and the risk of BM in newly diagnosed breast cancer patients is unknown. Methods: To determine incidence of BM in HER-2/neu over-expressing breast cancer patients, a cohort of patients between 01/1998 and 12/2003 with uniform HER-2/neu testing were identified from a cancer registry. A total of 460 patients with HER-2/neu over-expression and 500 patients with HER-2/neu negative disease were reviewed. Patients were excluded if there was breast cancer diagnosed before 01/1998 or others cancer. A total of 301 HER-2/neu over-expressing and 363 HER-2/neu negative patients were included for this analysis. The association between histological features and the occurrence of BM were evaluated with univariate and multivariate analyses. Results: BM were identified in 8% (24 patients) of HER-2/neu over-expressing breast cancer patients compared to only 1.7% (6 patients) in the HER-2/neu negative patients (hazard ratio 5.15 [2.079–12.78], p=0.0001). In patients with recurrent disease, the proportion of BM for HER-2/neu over-expressing patients was 24% compared to 10% in HER-2/neu negative patients. HER-2/neu over-expression, tumor size >2cm, ≥ 4 nodes positive and grade 2/3 were predictors of BM in univariate analysis. In multivariate analysis, HER-2/neu over-expression and tumor size>2cm were an independent prognostic factors for the development of BM, while hormone receptors expressions was protective (p=0.02). Conclusions: Our population based study show that newly diagnosed HER-2/neu over-expressing breast cancer patients are at significantly increased risk for BM. As most BM occur in HER-2/neu over-expressing patients with systemic metastatic disease, these findings could prompt consideration of brain prophylaxis strategies and/or serial radiologic screening to detect asymptomatic BM. No significant financial relationships to disclose.

10670 Background: T combined with weekly H confers greater tumor response and survival compared to T monotherapy in P with Her-2 positive MBC. A recent report has demonstrated that H can be administered q3wks. The primary endpoint is to evaluate time to progression (TTP). Sencondary objectives are response rate, overall survival and safety profile. Methods: P cytologically or histologically confirmed of metastatic breast cancer, HER-2 positive (+++ by Herceptest, or FISH positive), age > 18, ECOG PS ≤ 2, and adequate organ function, were included. Prior chemotherapy for MBC or adjuvant anthracycline-based regimen in the previous 6 months was not allowed. Treatment: T 100 mg/m2 iv D1 q3wks for 6 cycles, H 8 mg/kg (cycle 1) and 6 mg/kg (consecutive cycles) iv D1, q3wks. P may receive H monotherapy until PD at the investigator criteria. Results: Over 41 analyzed P, median age was 57 years (29–75); ECOG PS 0–1 95% and ductal carcinoma 88%. Twenty five P received prior chemotherapy. Treatment: 217 cycles of TH (median 6) were administered. After that, 23 P received 189 cycles of H monotherapy (median 5, 1–32). During TH treatment median RDI was 97% for T and 96% for H, and it was 99% during H treatment. Over 33 P for efficacy analysis (2 consent withdrawal, 1 allergic reaction, 1 ongoing and 4 response not confirmed by RECIST criteria), 6 achieved CR and 12 PR, for an ORR of 54.6% (95% CI: 37.6–71.6). Median follow-up time was 11.8 m and median TTP was 8.8 m (95% CI, 1.9–15.6). All P were evaluable for safety. During TH treatment, grade III/IV neutropenia occurred in 16 cycles (7.4 %), 14 of them were febrile neutropenia episodes (6.5%). Other grade III/IV toxicities per cycle were: leucopenia (5.5%), hyperglycemia (2.3%), anorexia (2.3%) and skin (2.3%). During H monotherapy treatment, the only grade III-IV toxicities observed were, skin (1.6%), oedema (1.1%), nail disorders (0.5%) and malaise (4.3%). Six P (14.6%) dropped out due to cardiac toxicity: 5 had LVEF under 50% and one atrial fibrillation. Conclusions: Preliminary results suggest that TH q3wks followed by H as single agent, is an effective regimen for the treatment of P with Her2 positive MBC. No significant financial relationships to disclose.

650 Background: HER2/neu over-expression (HER2+) occurs in approximately 25% of breast cancers and is often associated with a more aggressive disease. In this study we examined the effects of hormo...

872 Background: The elderly population in the United States is growing. There is enough evidence to suggest that elderly patients with cancer, who has good performance status, should be treated equally aggressively as younger patients. Based on these facts a retrospective analysis was done to look at the demographic difference in elderly patients with breast cancer. Methods: Records of 120 patients with breast cancer diagnosed and treated in rural Kentucky were analyzed for their demographics. Subsequently a comparison was done between patient groups of age younger than 70 years (Group-I) and age 70 years and older (Group-II). Results: Ninety-six patients were in Group-I and thirty-four patients were in Group-II. The oldest patient seen was 89 years of age. The important findings were as follows. An interesting observation was seen in six patients who were age 80 years or over. Four had stage II disease, four were hormone receptor negative, of which three had 2–3+ over expression of her2neu by immunohisto...

4155 Background: Over expression of the cyclooxygenase-2 (COX-2) enzyme has been reported in 90% of patients (pts) with pancreatic cancer. COX-2 derived prostaglandins contribute to tumor growth th...

6567 Background: Studies of B-CLL gene expression profiling revealed a phenotype mainly related to experienced B cells, although only a B-CLL subset has IgVH gene mutations. Methods: We investigate...

9686 Background: Alternatives to surgical prophylaxis are hardly needed in women with a hereditary risk of breast cancer. The aim of this study was to screen BRCA1-related and sporadic breast tumors and non-tumor distant breast tissues for alterations susceptible to be targets for chemoprevention. Methods: 25 breast samples of BRCA1 mutation carriers and carefully matched sporadic controls were selected from the tumor bank of our institution. Tumor samples were screened using a tissue array, and normal and intermediate tissues from the same individuals by standard immunohistochemistry (IHC). Results: Both groups were comparable regarding the matching criteria: age (med 39 and 41), tumor size (med 23 and 22 mm), SBR grade (grade 3: 76 and 71%), histological type. In tumors, p53 over expression and high Ki67 expression rates did not differ between both groups, while PR (12 vs 38%, p=0.03) and, to a lesser extent, ER (p=0.08) were less often expressed in BRCA1-related tissues than in controls. In normal tiss...