Perez, EA

Abstract Background: Prediction of benefit from trastuzumab in patients (pts) with HER2+ breast cancer remains an important goal. We sought to investigate the predictive value of quantitative measurement of HER2, HER3, HER4, EGFR, ER and PTEN protein expression on the benefit of trastuzumab in the phase III HER2+ adjuvant N9831 study for pts randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C). Methods: For each marker, we evaluated quantitative expression, relationship with demographic data, and association with disease-free survival (DFS) of pts. Freshly cut tissue microarray slides with up to three-fold redundancy per specimen from the N9831 cohort were treated identically using the AQUA (Camp, et al; Nat Med 2002, JCO 2008) method of quantitative immunofluorescence for each marker. HER2 was tested with CB11 (mouse monoclonal, Biocare, Inc.) and preliminary results were available for 698 of nearly 1400 pt specimens to be tested. The minimum value per pt was used in statistical analysis. Specimens were classified with high versus low expression based on a median value cutpoint for each marker. Median follow-up was 7.0 yrs. Results: Quantitative HER2 was compared with centrally performed HER2 testing by IHC and FISH. Median quantitative HER2 via AQUA was 10,017 units for the HER2 IHC 3+ group (n=607) versus 1058, 831, and 970 for the HER2 IHC 2+ (n=68), 1+ (n=11), and 0 (n=11) groups, respectively. The Spearman correlation between quantitative HER2 and FISH HER2/CEP17 ratio was 0.32 (p<0.001). High quantitative HER2 was associated with lower percentage of hormone receptor positivity (48% vs 59%, chi-sq p=0.003) but not associated with age, race, nodal positivity, tumor histology, grade, or size. High HER2 did not impact DFS in any arm of the study (See Table). Data for additional HER2 testing, HER3, HER4, EGFR, ER and PTEN are in process and will be ready by September, 2011. Conclusions: Similar to results based on standard HER2 testing by IHC and FISH in N9831, quantitative HER2 did not impact benefit from adjuvant trastuzumab. Results for additional markers will be presented. Our complete quantitative results for a second epitope on HER2, HER3, HER4, ER and EGFR will be the first report of these markers in a large patient cohort in the adjuvant setting. Disease Free Survival Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-03.

Abstract Background: T-DM1, an antibody-drug conjugate composed of trastuzumab, a stable linker, and the cytotoxic agent DM1, is in development for the treatment of HER2−positive cancers. Single-agent T-DM1 3.6 mg/kg every 3 weeks (q3w) has demonstrated clinical activity in 2 phase II studies (TDM4258g and TDM4374g) in patients with pretreated HER2−positive MBC. The efficacy and safety of T-DM1 vs trastuzumab + docetaxel was investigated in patients with no prior MBC treatment in the randomized phase II study TDM4450g/BO21976. Here we report the PK of T-DM1 from that study and compare these data with those from studies that enrolled pretreated patients. Methods: In all 3 studies, PK parameters, including maximum concentration (Cmax), area under the concentration-time curve (AUC), terminal half-life (t½), steady-state volume of distribution (Vss), and clearance (CL) were estimated by noncompartmental analysis (NCA) for serum T-DM1, serum total trastuzumab (conjugated and unconjugated), and plasma DM1. The effects of baseline trastuzumab and HER2 extracellular domain (ECD) concentration on T-DM1 exposure were explored and the relationship between T-DM1 exposure and clinical response (objective response rate [ORR] and progression-free survival [PFS]) was modeled. Results: T-DM1 PK from evaluable patients enrolled in 3 studies are shown in Table 1. No significant correlations were observed between efficacy (as measured by ORR) and T-DM1 exposure (AUC, Cmax) after administration of T-DM1 to pretreated patients; efficacy-exposure analyses (ORR and PFS) for previously untreated patients will be presented. Patients with measurable concentrations of trastuzumab at baseline had a greater AUC during cycle 1; however, this did not impact ORR. Baseline circulating HER2 ECD concentrations also had no effect on ORR for pretreated patients. The impact of baseline trastuzumab and HER2 ECD concentrations on ORR and PFS in previously untreated patients will be presented. Conclusions: Single-agent T-DM1 has similar PK in patients who have received prior therapy for MBC and in those who have not. The PK of T-DM1 was not affected by prior trastuzumab treatment or by circulating HER2 ECD, and no significant correlations were observed between efficacy (ORR) and T-DM1 exposure (AUC, Cmax) or HER2 ECD for pretreated patients. The relationships between efficacy and T-DM1 exposure and HER2 ECD concentrations will be presented for patients without prior MBC treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-13.

Abstract Background Tumors that are negative for estrogen and progesterone receptors and do not over express HER2 are referred as “triple negative” breast cancer (TNBC). These tumors are characterized by unique molecular profiles on gene expression arrays, aggressive behavior with a high recurrence rate, an increased risk of visceral metastases, poor prognosis and lack of targeted therapies. Brostallicin is a novel synthetic compound from the class of DNA minor groove binding (MGB) anti-cancer agents. It retains activity in cancer cells resistant to alkylating agents, topoisomerase I inhibitors and is fully active against DNA-mismatch repair deficient tumor cells. Cells expressing relatively high glutathione/glutathione S-transferase (GSH/GST) levels are more susceptible to brostallicin antitumor efficacy. Cisplatin administration increases expression of GST in tumor cells leading to an increased anti-tumor efficacy of brostallicin. Trial design: Single-stage phase II study — based on the effects of cisplatin on GSH/GST levels in preclinical models, the most reasonable sequence to explore was cisplatin on Day 1 followed by brostallicin on Day 2 repeated every 21 days. Eligibility criteria: Women or men ≥18 years of age with confirmed adenocarcinoma of the breast with clinical evidence of measurable metastatic disease and triple negative subtype according to current ASCO CAP guidelines [ER/PR ≤1%; HER2 negative), who received 0–4 prior chemotherapy regimens in the metastatic setting; with adequate hematologic, renal and hepatic functions; and no active CNS metastases. Aims: To study the efficacy of the novel drug, brostallicin, as well as to serve as proof of concept of its mechanism of action in TNBC. The primary endpoint is to evaluate clinical efficacy of the combination of brostallicin and cisplatin in the treatment of patients with metastatic TNBC, as measured by progression-free survival (PFS) at 3 months with 89% power (0.10 significance level) to detect an absolute difference of 20%. Secondary endpoints include ORR by RECIST, duration of response, 6-month PFS, overall survival (OS) and adverse event profile. Tertiary endpoints include assessment of 1) GSH levels prior to the administration of cisplatin and of brostallicin; and 2) the prevalence of BCRA-1 mutation by IHC in the primary or metastatic tumor. Statistical methods: The largest 3-month PFS proportion where the proposed treatment regimen would be considered ineffective in this population was estimated at 35% based on the median PFS of 60 days in patients with metastatic TNBC enrolled in the N0234 trial (erlotinib and gemcitabine as 1st/2nd line), and the smallest 3-month PFS success proportion that may warrant subsequent studies with the proposed regimen in this patient population was estimated at 55%. The interim analysis will be reported when the 20th eligible patient has been followed for 3 months. Present accrual and target accrual: 21 patients have been accrued at the time of abstract submission (June 2011). Target accrual is 42 evaluable patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-14.

Abstract Identification of HER2 as an important cellular marker in the biology and treatment of breast cancer has highlighted the importance of reliable testing methodology. Controversy exists regarding type of test, reliability, definition of positivity, and which test may best predict for patient (pt) efficacy to anti-HER2 therapies. Purpose: To determine the concordance between HER2 results by 3 central laboratories, impact of round-robin adjudication of discordant cases, and heterogeneity in HER2 results using specimens from 3 adjuvant trials where HER2 testing was performed by local and central laboratories for enrollment. Methods: We performed a blinded round-robin exchange of randomly sampled, HER2-normal (IHC-& FISH-) and HER2-positive breast tumors among 3 central laboratories (NCCTG, BCIRG and NSABP) for confirmatory HER2 testing. The 3 laboratories performed immunohistochemistry (IHC) for HER2 using the HercepTest kit (Dako, Carpenteria, CA) and fluorescence in situ hybridization (FISH) for HER2 using the PathVysion HER2 DNA probe kit/HER2/CEN17 probe mixture (Abbott Molecular, Des Plaines, IL) on 389 tumor specimens obtained from N9831/BCIRG006 (37 IHC+/FISH+, 33 IHC+/FISH-, 36 IHC-/FISH+, 62 IHC-& FISH-) and BCIRG005 (96 IHC-& FISH-); 123 cases had ≥2 blocks examined from the same pt. HER2 positivity was defined according to FDA-approved guidelines used in the clinical trials (IHC+: 3+ complete membrane staining in >10% cells; FISH+: HER2/CEN17 ratio ≥2.0). The HER2 status (IHC: 3+ vs 0-2+; FISH: amplified vs not) for each block was independently determined at each site; discordant IHC and FISH cases were adjudicated at a face-to-face meeting. Results: Independent reads were concordant across pathologists in IHC status in 351/381 (92%) cases and in FISH status in 343/373 (92%) cases. Upon adjudication, a consensus was reached on 16 and 18 of the discordant IHC and FISH cases, respectively. Among 96 BCIRG005 cases, IHC-and FISH-were confirmed in the primary block in all 96 cases. Among 59 evaluable N9831 HER2-normal cases, IHC-and FISH-were confirmed in the primary block in 57 (97%) cases (but another block tested HER2+ for 4 cases). Among 102 N9831/BCIRG006 HER2+ cases, HER2 positivity was confirmed in the primary block in 73 (72%) cases. Among 118 cases with IHC results for > 1 block, the adjudicated IHC result agreed across blocks in 106 (90%) cases. Among 113 cases with FISH results for >1 block, the adjudicated FISH result agreed in 107 (95%) cases. Among 53 N9831 HER2-normal cases adjudicated as IHC-& FISH-(although they all had a previous local HER2+ test), there was significant improvement in disease-free survival associated with trastuzumab given concurrently with paclitaxel after doxorubicin and cyclophosphamide compared to chemotherapy alone (HR=0.31, 95% CI 0.11-0.91; A 23 pts, 10 events; C 30 pts, 5 events). Conclusions: Excellent agreement (96%) was observed among the pathologists at adjudication, suggesting that standardized methods improve assay proficiency. HER2 heterogeneity across blocks was observed more at the protein than at the gene level. In the small subset of N9831 pts adjudicated as HER2-normal trastuzumab benefit was observed. This work was supported by NCI and Genentech. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD10-02.

Abstract In the Breast International Group (BIG) and North Central Cancer Treatment Group (NCCTG) co-led phase III adjuvant breast cancer trial, ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation), two central laboratories, the European Institute of Oncology (IEO; Milan, Italy) and Mayo Clinic (Rochester, MN), are responsible for confirming the human epidermal growth factor receptor-2 (HER2), estrogen receptor α(ER), and progesterone receptor status of the primary breast tumors for the Rest of World (excluding China, which conducts a separate central review) and North American patients, respectively, prior to patient study entry. As of December 2009, discordance in HER2 and ER testing between local and central laboratories was observed by both central laboratories. For IEO, 14.5% of 8,037 HER2 cases locally positive [by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)] were not able to be confirmed as centrally positive; whereas for Mayo, 5.8% of 412 HER2 cases locally positive were not able to be confirmed as centrally positive (Table 1). Central and local IHC ER discordance was 12.1% and 11.7% for 9,021 IEO screened cases and 419 Mayo screened cases, respectively (Table 2). In particular, IEO observed more false-positive (locally positive/centrally negative) HER2 findings than Mayo and Mayo observed more false-positive ER findings than IEO. Purpose: Motivated by the above findings, we launched a ring study to assess whether the central lab results of a subset of local/central discordant ALTTO cases could be confirmed in the other central lab. Methods: IEO and Mayo exchanged and retested a subset of FFPE breast tumors collected in ALTTO. IEO sent 20 HER2 false-positive, 5 ER false-positive, and 5 ER false-negative (locally negative/centrally positive) ALTTO breast tumors to Mayo. Mayo sent 5 HER2 false-positive, 20 ER false-positive, and 5 ER false-negative ALTTO breast tumors to IEO. IEO and Mayo performed IHC for ER according to their own methodology: DAKO cocktail of ER 1D5 and 2.123 monoclonal antibodies and monoclonal ER 1D5 antibody, respectively. The two laboratories performed IHC for HER2 according to the HercepTest® manufacturers’ instructions (Dako, Carpenteria, CA) and FISH for HER2 using the PathVysion HER2 DNA probe kit and the HER2/centromere 17 probe mixture (Abbott Molecular, Des Plaines, IL). Results: IEO and Mayo confirmed the central HER2-negative result in 100% of 25 cases. Analyses of ER are ongoing and ER results will be presented. Conclusions: In this subset of patients, enrollment ineligibility did not change when HER2 testing was performed by either IEO or Mayo Clinic central laboratories. Table 1. HER2 Local/Central Lab Results Table 2. ER Local/Central Lab Results Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-36.

Abstract Abstract #76 Background: QOL and MH outcomes were integrated into the NSABP B-30 trial as secondary outcomes to the efficacy analyses which are being presented separately. Explicit secondary aims of the NSABP B-30 study were 1) to compare toxicities among the regimens, 2) to compare QOL, and 3) to examine differences in amenorrhea and its relationship to symptoms, QOL, and efficacy. Here we examine the secondary aims of the study as a companion to the efficacy results that are presented separately.
 Materials and Methods: 5351 pts with cT1-3, N0-1, M0 were enrolled from 3/1/99 to 3/31/2004. 2170 were enrolled on the QOL study, and 2449 were enrolled on the MH study and were randomized to one of three treatment groups: Group 1 [doxorubicin (A) 60 mg/m2 and C 600 mg/m2 q 3 weeks (wks) x 4 followed by docetaxel (T) 100 mg/m2 q 3 wks x 4; Group 2 [A 50 mg/m2 and T 75 mg/m2 q 3 wks x 4]; Group 3 [A 50 mg/m2 T 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 q 3 wks x 4]. All patients with ER-positive tumors received hormonal therapy after completing chemotherapy. Preliminary results from Group 1 have been reported previously (Swain, et al. Breast Cancer Res Treat, 2008).
 Results: The protocol specifies that 800 deaths are required for the definitive analysis of treatment, QOL, and MH outcomes, which are expected to occur by fall 2008. For this final report, results from a comparison of the three arms will be analyzed and presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 76.

Abstract Abstract #75 Background: The primary aims of this study were to determine 1) if a concurrent regimen of therapy containing cyclophosphamide compared to a sequential regimen containing cyclophosphamide would prolong disease-free survival (DFS) and overall survival (OS) and 2) if a regimen without cyclophosphamide was at least as efficacious as the two regimens containing cyclophosphamide. The secondary aims were to compare toxicities among the three regimens and to compare differences in amenorrhea in premenopausal women in each arm and its relationship to outcome.
 Materials and Methods: 5351 pts with cT1-3, N0-1, M0 were enrolled from 3/1/99 to 3/31/2004. 1783 pts were randomized to Group 1 [doxorubicin (A) 60 mg/m2 and C 600 mg/m2 q 3 weeks (wks) x 4 followed by docetaxel (T) 100 mg/m2 q 3 wks x 4], 1784 pts to Group 2 [A 50 mg/m2 and T 75 mg/m2 q 3 wks x 4], and 1784 to Group 3 [A 50 mg/m2 T 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 q 3 wks x 4]. All patients with ER-positive tumors received hormonal therapy after completing chemotherapy. The protocol specifies that 800 deaths are required for the definitive analysis. This is expected to occur by Fall 2008.
 Results: Mean time on study is currently 79 months. At entry, 46% of pts were < 49 yrs; 54% were > 50 yrs. 82% were white, 10% black, 4% Hispanic. 66% had 1-3 positive nodes, 26% had 4-9, and 8% had 10+. 75% of pts were ER pos. 49% had lumpectomy, 51% mastectomy, and 24% local/regional radiotherapy. Mean tumor size was 2.5 cm. The presentation will include the first results of DFS, OS, and relevant toxicities from the trial. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 75.

Abstract Abstract #6149 Background: Internal Review Boards and Data and Safety Monitoring Boards often require protocol-specified adverse event (AE) stopping rules for safety monitoring. However, availability of safety data for investigational agent(s) may be limited at the time of protocol development in the phase II setting. This meta-analysis was undertaken to quantify the variability of AE rates in North Central Cancer Treatment Group (NCCTG) phase II metastatic breast cancer (MBC) clinical trials and to investigate whether study factors are associated with AE rates for the development of AE stopping rules in future phase II clinical trials.
 Methods: All closed NCCTG phase II MBC clinical trials using CTC v2.0 or CTCAE v3.0 for AE monitoring were selected. Rates of G3/4 AEs (overall, hematologic [H], and non-hematologic [NH]) and of study discontinuation [SD] due to AEs were calculated for each trial. Associations between study factors [number of agents (single vs combination); line of therapy (first-line only vs other); and type of therapy (chemotherapy vs other)] and AE rates were assessed via Wilcoxon rank sum tests.
 Results: 15 trials met inclusion criteria. 7 used CTCAE v3.0; 6 investigated single agents; 5 investigated first-line therapy; and 11 investigated chemotherapy regimens. 694 pts were evaluable for AE analysis. The G3/4 AE rate across trials was 68% (16-98%) overall, 45% (0-96%) H, and 51% (16-78%) NH. The overall rate of SD due to AEs was 13% (0-40%). The overall rate of G3/4 AEs was significantly lower in single agents vs combination regimens (30% vs 86%, p=0.004). This association held for H (2% vs 66%, p<0.0001) and NH (27% vs 57%, p=0.03) Aes. The rate of SD due to AEs was also significantly lower in single agents vs combination regimens (0.5% vs 15%, p=0.04). The rate of G3/4 AEs was significantly higher in first-line only trials vs other trials (overall: 90% vs 47%, p=0.04; H: 73% vs 5%, p=0.02; NH: 66% vs 41%, p=0.08). The rate of SD due to AEs was also significantly higher in first-line only trials (18% vs 4%, p=0.008). The only significant association with chemotherapy vs other therapy was G3/4 H AE rates (51% vs 2%, p=0.02).
 Discussion: High variability in G3/4 AE rates overall and in H and NH AEs was noted in these 15 trials. There is also high variability in the rates of SD due to AEs. The data suggest that clinical trials with single agent regimens have lower AE rates than combination regimens and, surprisingly, trials of first-line therapy only have higher AE rates than other trials. This may be due to more aggressive therapy being tested in the first-line setting. Although data from previous trials with the investigational agent(s) should be used for developing AE stopping rules when available, this study suggests that study factors such as number of agents and line of therapy can be useful when previous data are limited. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6149.

Abstract Abstract #6147 Background: Phase II metastatic breast cancer (MBC) clinical trials evaluating efficacy of cancer treatments are often designed using a binary primary endpoint (i.e., each evaluable patient [pt] is classified as a “success” or “failure”). In the era of novel agents in cancer research, endpoints such as 6-month progression-free survival [PFS6] for measuring efficacy of cytostatic agents are more commonly being used. This meta-analysis was undertaken to compare two binary classifications of PFS6 and to compare these binary endpoints with other efficacy endpoints in the phase II setting.
 Material and Methods: All closed North Central Cancer Treatment Group (NCCTG) phase II MBC clinical trials using Response Evaluation Criteria in Solid Tumors (RECIST) with at least 1 year of follow-up since last pt accrued were selected. All eligible pts initiating treatment were included. Two binary classifications of PFS6 were computed for each trial. Success for PFS6-1 is defined as on study treatment 6 months from registration without documentation of disease progression. Success for PFS6-2 does not require a pt to be on study treatment at 6 months. Also computed for each trial are Kaplan-Meier (KM) estimates of PFS6 (PFS6-KM) and 1-year overall survival (OS1-KM). Trial-level endpoints were summarized using descriptive statistics and compared using weighted (by trial sample sizes) Pearson correlations. Lastly, the concordance rate of PFS6-1 and PFS6-2 status with OS status at 1 year at the pt level was computed across all pts (pts censored for OS prior to one year were excluded [n=10]).
 Results: 11 trials met inclusion criteria. All trials required measurable disease and had a single arm. 485 evaluable pts were accrued (median 48 pts per trial [range 19-77]). Median PFS6-1 was 27% (range 10-44%) and median PFS6-2 was 34% (range 10-73%). The median trial-level difference between PFS6-1 and PFS6-2 was 5% (range 0-43%). The correlation between PFS6-1 and PFS6-2 was 0.81 (p<0.01). Among the endpoints, PFS6-2 and PFS6-KM had the highest correlation (>0.99, p<0.01) due to only 2 pts being censored for PFS prior to 6 months. Among the PFS endpoints, OS1-KM was most highly correlated with PFS6-1 (0.79, p<0.01) with the correlations with PFS6-2 and PFS6-KM not being statistically different from zero (both 0.59 with p>0.05). However, overall patient-level concordance between PFS6 status and OS status at 1 year was higher using PFS6-2 (68%) than PFS6-1 (59%).
 Discussion: Differences were observed between the two binary classifications of PFS6. PFS6 with (as compared to without) the requirement that a pt be on study treatment at 6 months appears to have higher correlation with OS at 1 year at the trial level but lower concordance with OS status at 1 year at the pt level. Selection of the historical control should take into consideration the definition of PFS6 being used. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6147.

Abstract Abstract #56 Background: Recent findings from NSABP B-31 suggested that breast cancer (BC) patients (pts) with c-MYC (MYC)/HER2 co-amplification in their primary tumors may benefit more in terms of disease-free survival (DFS) from adjuvant trastuzumab (n=471; p<0.0001, HR 0.24; 13 vs. 51 events) than those pts with only HER2 amplification in their primary tumors (n=1078, p=0.007, HR 0.63; 55 vs. 82 events).
 Purpose: The overall objective of this analysis is to determine the association between MYC/HER2 co-amplification and outcome of pts randomized to receive chemotherapy alone (Arm A) or chemotherapy with concurrent trastuzumab (Arm C) on N9831.
 Patients/Methods: This analysis included 868 pts from the HER2+ NCCTG N9831 Intergroup adjuvant trastuzumab phase III clinical trial on Arms A or C. Fluorescent in situ hybridization (FISH) was performed at a central laboratory, Mayo Clinic Clinical Cytogenetics Laboratory, using dual probe mixtures for HER2 (17q11.2-12/centromere 17) and for MYC (8q24/centromere 8). The HER2 amplification status in whole tissue sections was evaluated to determine eligibility of pts for N9831. Tissue microarrays containing three cores from each patient's tumor were analyzed for MYC amplification status. The gene and centromere copy number as well as the distribution of the signals for each marker were determined in sixty non-overlapping interphase nuclei.
 Results: Of 273 pts with completed FISH analyses, 34 (12%) pts had MYC amplification. The rate of MYC amplification was similar across arms (18/135 [13%] vs. 16/138 [12%]; ChiS p=0.66). Co-amplification of MYC/HER2 was observed in 32 (12%) pts with similar co-amplification rates across arms (17/135 [13%] vs. 15/138 [11%]; ChiS p=0.66). Based on preliminary analyses, MYC amplification and MYC/HER2 co-amplification do not appear to be associated with race, menopausal status, hormone receptor status, nodal status, tumor histology, tumor grade, or tumor size (all ChiS p>0.05); however, MYC amplified pts were significantly younger than MYC non-amplified pts (mean 46.4 vs. 51.0, t-test p=0.02) and MYC/HER2 co-amplified pts were significantly younger than MYC/HER2 non-co-amplified pts (mean 45.9 vs. 51.0, t-test p=0.01).
 Conclusions: In our initial analyses of 239 pts, we observed a lower frequency of MYC/HER2 co-amplification than the previously reported 30% for NSABP B-31. Complete FISH analyses of 868 pts in N9831 and association with DFS will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 56.