bluuebunny/crossref_metadata_2025_split huggingface dataset:
European and North American scientific meetings under review: presentation and subsequent publication of breast cancer related abstracts in peer-reviewed journals.
Authors: Costa SD , Ignatov AS , Bischoff J , Taran AF 
Published: December 2010

Abstract
Abstract #3115
Introduction: The number of scientific meetings with breast cancer-related topics increases constantly and therefore so does the number of presented abstracts. Many of these abstracts are not reported in peer-reviewed journals post-conference. This lack of final publication constitutes a loophole in scientific reporting. Furthermore, it retrospectively assesses the quality of the review process the abstracts undergo prior to the meetings. We critically reviewed the publication rates of breast cancer-related abstracts submitted to the four major oncology meetings for breast cancer in Europe and North America in 2002.&#x2028; Material and methods: The authors identified all breast cancer-related abstracts presented or published at the annual meetings of the ASCO, SABCS, EBCC and ESMO in 2002. First, a MEDLINE search identified the abstracts written by the first, second and last authors that matched a journal article by these authors. Second, the match between the study described in the abstract and full publication was determined.&#x2028; Results: A total number of 1620 abstracts were analyzed.&#x2028; Mean rate of full publication: 44,5%; publication rate of EUR meetings: 33,3%; publication rate of NA meetings: 52,7% (p&lt;0,001). Median time to full publication: 11,55 months (CI 95%;7,58 to 15,66 months; full publication for the EUR meetings: 8,59 months; full publication for the NA meetings: 13,44 months (p&lt;0,001). Median impact factor publishing journals: 1,95 IP (CI 95% 0,9 to 2,77 IP), published abstracts of the EUR meetings: 1,09; published abstracts of the NA meetings: 2,5(p&lt;0,001). Estimated probability for an abstract not to be published after 60 months: 55,5%; abstract of the EUR meetings: 67,5%; abstract of the NA meetings: 47,8%(p&lt;0,001) (Figure).&#x2028; Discussion: We found that only about half of all studies first presented as abstracts at major meetings were published as full papers later. Thus, those who rely on scientific evidence to make health care decisions are faced with a biased subset of scientific evidence. It is clear that full-paper reviewing in peer-reviewed journals is more complex and increases the scientific value of a paper in comparison to a meeting abstract. In the past few years the number of scientific meetings on breast cancer and the number of participants attending those has increased dramatically. Our study demonstrated that this does not imply for the quality of the presented data. We propose that scientists who publish their work in peer-reviewed journals should avoid citation of abstracts and/or talks presented even at major international meetings because they risk to rely on data that has not between reviewed thoroughly enough.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3115.
Randomized phase III study of trastuzumab monotherapy followed by docetaxel and trastuzumab versus the combination of trastuzumab and docetaxel as first-line treatment in patients with HER2 positive metastatic breast cancer.
Authors: Najagami K , Inoue K , Mizutani M , Hozumi Y , Fujiwara Y , Masuda N , Tsukamoto F , Saito M , Ohashi Y , Sano M , Noguchi S 
Published: December 2010

Abstract
Abstract #3132
Introduction: Treatment with trastuzumab (H) is a standard therapy for the patients with HER2 positive metastatic breast cancer (MBC) and both the combination with H and chemotherapy (CT) and H alone are very popular. However, it is unknown which is better; sequential H alone followed by combination of CT and H at disease progression or the combination with H and CT as first-line therapy. Therefore, we conducted phase III randomized trial compared them in HER2 positive MBC.&#x2028; Methods: Eligible patients were HER2 positive MBC patients (pts) with measurable tumour based on RECIST, ECOG Performance status 0 or 1 and left ventricular ejection fraction (LVEF) &gt;50%. Patients with prior CT for MBC, adjuvant H, and Docetaxel (DTX) were excluded. They were randomly assigned to sequential weekly H 2 mg/kg (loading 4 mg/kg) alone followed by combination of DTX (60 mg/m2, q3wks) and H at disease progression (arm A) or concurrent combination of H and DTX (arm B). Primary endpoints were time to progression (TTP) of H alone (arm A) and combination of H and DTX (arm B) and overall survival (OS). Secondary endpoints were overall response rate (ORR), TTP and safety in arm A and B.&#x2028; Results:Of the 108 pts registered, 105 pts were eligible. Baseline characteristics of all pts in two groups were well-balanced. Median age was 57/55 years, prior adjuvant CT 38/45% and single metastatic site 30/31% in arm A and B, respectively. Median TTP in arm A was 137 days compared to 445 days in arm B (hazard ratio=4.15; P&lt;0.0001). ORRs were 15% and 71% in arm A and B, respectively. Median OS has not been reached yet, however, the number of deaths were 11 pts in arm A and 4 pts in arm B (hazard ratio=3.36; P=0.028). Adverse event incidence of grade 3 or 4 was 51/85% in each arm. An Efficacy and Safety Evaluation Committee recommended stopping this trial based on the results of TTP and OS.&#x2028; Discussion: These results suggested that the combination of H and CT is superior to sequential H alone followed by DTX and H as first-line therapy in HER2 positive MBC pts despite the number of pts did not reach to the planned sample size. We will continue further investigation based on extended follow-up period. The updated data will be presented.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3132.
Final results from a phase II evaluation of lapatinib (L) and bevacizumab (B) in HER2-overexpressing metastatic breast cancer (MBC).
Authors: Dickler M , Franco S , Stopeck A , Ma W , Nulsen B , Lyandres J , Melisko M , Lahiri S , Arbushites M , Koehler M , Rugo HS 
Published: December 2010

Abstract
Abstract #3133
Background:&#x2028; HER2 overexpression has been shown to upregulate VEGF expression in pre-clinical breast cancer models. Overexpression of both HER2 and VEGF has been associated with worse clinical outcome than overexpression of either receptor alone. In pre-clinical models, combination anti-HER2 and anti-VEGF therapy has been shown to be more effective than either treatment alone. B plus trastuzumab (T) has shown promising activity in patients (pts) with HER2+ MBC, however the cardiac toxicity of this regimen requires further study. L, an oral dual tyrosine kinase inhibitor of EGFR and HER2, is approved in combination with capecitabine after T-based therapy for HER2+ MBC. L may have less cardiac toxicity and may be a safer and more effective alternative to T. This hypothesis was evaluated in a phase 2 trial of L+B in HER2+ MBC pts.&#x2028; Methods: &#x2028; This single-arm study was designed to evaluate L (1500 mg PO daily) plus B (10 mg/kg IV q2wk) in 50 HER2+ MBC patients. The primary endpoint is crude progression-free survival (PFS) rate at 12 weeks with 84% power to detect a clinically significant PFS rate of 60%; secondary endpoints include toxicity and response per RECIST. Efficacy was assessed at Week 6, 12, and q12wks thereafter. HER2-overexpression was defined as local FISH-positive or IHC 3+ results. Serial evaluation of circulating tumor and endothelial cells and HER2 extracellular domain was performed.&#x2028; Results:&#x2028; Enrollment to this study ended in March 2008 (n=52). Data are presently available on 32 of 52 pts enrolled before January 1, 2008. Pts received a median of 5 prior MBC therapies (range 0-15); 88% received prior T (median 19.7 months; range 1.2-56.8 months). The most frequently reported AEs included diarrhea (81%), rash (66%), nausea (56%), fatigue (56%), and emesis (46%). Four asymptomatic LVEF declines were reported (three grade 2 events; one grade 1 event), as were nine cases of hypertension (eight grade 1 or 2 events; one grade 3 event) and one grade 3 GI hemorrhage. 27/32 patients were evaluable for response; five withdrew prior to first radiologic assessment (two due to toxicity, three due to investigator/pt request). The crude 12-week PFS rate was 63% (20/32 did not progress by Week 12); overall response rate (complete/partial response) was 13%, and the clinical benefit rate (complete/partial response or stable disease for ≥ 24 weeks) was 34%.&#x2028; Conclusions:L+ B is well tolerated and has shown promising activity in heavily pretreated HER2+ MBC pts. Final efficacy and safety data will be presented on the full study cohort.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3133.
Circulating regulatory (CD4+CD25+FOXP3+) T cells decrease in breast cancer patients after vaccination with an Ii-Key-modified class II HER2/neu peptide (AE37).
Authors: Gates JD , Benavides LC , Carmichael MG , Hueman MT , Holmes JP , Khoo S , Stojadinovic A , von Hofe E , Ponniah S , Peoples GE 
Published: December 2010

Abstract
Abstract #3134
Background: CD4+CD25+FOXP3+ regulatory T cells (Tregs) have been implicated in the suppression of immune responses against various tumors. To monitor the potential induction of Tregs in breast cancer (BrCa) patients receiving a modified HLA Class II HER2/neu peptide (AE37) vaccine in a clinical trial, we have analyzed peripheral blood lymphocytes (PBL) from vaccinated patients for the presence of Tregs and correlated our findings with ex vivo immune assays and in vivo delayed type hypersensitivity (DTH) responses to the vaccine. Methods: Fifteen BrCa patients have completed 6 monthly injections of the AE37+GM-CSF vaccine in a dose escalation safety study. The AE37 peptide consists of a HER2/neu peptide (776-790) linked to the Ii-Key moiety of the HLA Class II-associated invariant chain, which enhances epitope interaction with the Class II molecule. PBL obtained pre- and post-vaccination were stained with anti-CD4/CD25 (n=15) and FOXP3 (n=9) antibodies (PCH101 and 236A/E7) and analyzed by flow cytometry. Cells were also stimulated ex vivo with AE37 peptide to measure IFN-γ ELISPOT, proliferation (3H-thymidine-cpm) and cytokine secretion (TGF-β). DTH responses to the AE37 peptide pre- and post-vaccination were also recorded. Results: The mean CD4+ and CD4+CD25+ T cell populations for all patients (n=15) did not change from pre- to post-vaccination (CD4+ = 52.3+3.3% vs. 50.5+3.9%, p=0.6; CD4+CD25+ = 1.9+0.2% vs. 2.4+0.5%, p=0.2). Tregs (CD4+CD25+FOXP3+) were reduced in all 9 patients tested pre- to post-vaccination for both FOXP3 antibodies (Ab) (FOXP3 Ab1 = 2.1+0.2% vs. 1.1+0.1%, p=0.002; FOXP3 Ab2 = 2.0+0.2% vs. 1.0+0.2%, p=0.0009). There was no difference in pre- to post-vaccination levels of TGF-β (2720+582 pg/ml vs. 3387+848 pg/ml; p=0.9). AE37-specific proliferative responses increased from pre- to post-vaccination (34+23cpm vs. 6427+1431 cpm; p&lt;0.001). ELISPOT demonstrated an increased response from pre- to long term (6-12mo.) post-vaccination (Median – 2 vs. 34 spots/106 cells; p=0.003). DTH responses increased in all patients from pre- to post-vaccination (3.6+1.4 mm vs. 56.0+9.4 mm; p&lt;0.0001), and there appeared to be an inverse relationship between the degree of Treg reduction and the size of DTH response to AE37 (R2=0.83).&#x2028; Discussion: The novel AE37 HER2/neu peptide vaccine does not result in increased levels of Tregs. Furthermore, the reduced levels of Tregs in vaccinated patients appear to be associated with more robust responses in ex vivo immune assays and in vivo DTH reactions suggesting that the AE37 vaccine may be clinically useful.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3134.
A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer.
Authors: Krop IE , Mita M , Burris HA , Birkner M , Girish S , Tibbitts J , Holden SN , Lutzker SG , Modi S 
Published: December 2010

Abstract
Abstract #3136
Background: T-DM1, a novel HER2 antibody-drug conjugate (ADC) in development for HER2+ breast cancer (BC), combines activity of trastuzumab (T) with the targeted delivery of maytansinoid DM1 (potent antimicrotubule agent) to HER2-expressing cells. DM1 binds tubulin competitively with vinca alkaloids, 20-100x more potently than vincristine. It is bound to T by MCC, a linker that is stable with protease activity and under many pH or redox conditions. T-DM1 is the first ADC with an MCC linker to enter clinical trials. Main preclinical AEs were reversible transaminase (TA) elevations, reversible platelet decreases, and neuropathy. A phase I study of T-DM1 every 3 wks (q3w) in patients (pts) with advanced HER2+ BC who progressed on T-containing chemotherapy regimen, the maximum tolerated dose (MTD) was 3.6 mg/kg, with DLT of grade (Gr) 4 thrombocytopenia (TCP); tumor responses were seen in 5 of 9 pts (4 confirmed, 44%) with measurable disease treated at MTD. We undertook this dose escalation study of T-DM1 given once/wk (q1w) to explore pharmacokinetics (PK), safety, and tolerability of more frequent dosing.&#x2028; Methods: Pts with advanced HER2+ BC who had progressed on a T-containing chemotherapy regimen received T-DM1 IV q1w continuously. Dose levels were escalated in successive 3+3 cohorts if DLT was seen in &lt;1/3 of pts within 21 days of Cycle 1 Day 1.&#x2028; Results: As of 19 May 2008, enrollment is complete with 27 pts (15 at the MTD). Data is available for 19 pts [median age 54.0 (range 41-71); all PS 0-1; median number prior metastatic chemo agents 5.0 (range 2-8); median wks of prior trastuzumab 122 (range 29-325)] who have received 246 doses of T-DM1 at 1.2, 1.6, 2.0, 2.4, and 2.9 mg/kg. Common related AEs include fatigue (Gr1, 3 pts; Gr2, 4 pts; Gr3, 1 pt), thrombocytopenia (Gr 1, 4 pts; Gr2, 3 pts; Gr3, 2 pts), nausea (Gr1, 7 pts; Gr 2, 1 pt), TA elevations (Gr1, 1 pt; Gr2, 4 pts; Gr3, 1 pt), vomiting (Gr1, 3 pts; Gr2, 1 pt) and headache (Gr1, 2 pts; Gr2, 1 pt). Dose-limiting toxicity was seen in 2 pts at 2.9 mg/kg (toxicity preventing retreatment on Cycle 1 Day 8, from Gr2-3 thrombocytopenia). No Gr4 AEs or cardiac toxicity were seen. Preliminary PK analyses suggest that steady-state T-DM1 exposure at 2.4 mg/kg q1w will be ∼2x that associated with 3.6 mg/kg q3w. Of 15 pts evaluable for response, 9 had partial responses (8 confirmed, 53%).&#x2028; Conclusions: The MTD of T-DM1 on a weekly schedule is 2.4 mg/kg. Related Gr ≥2 AEs were reversible and manageable. The activity and safety results observed on q1w dosing were consistent with q3w dosing, supporting further study. Three Phase II trials of q3w T-DM1 in advanced HER2+ BC will enroll pts in 2008; preliminary results from the first trial will be reported in 2008.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3136.
Optimal method of dosing HER2/neu peptide vaccines: U.S. Military Cancer Institute Clinical Trials Group Study 1-01, 1-02, 1-03, and 1-04.
Authors: Benavides LC , Gates JD , Holmes JP , Mittendorf EA , Ponniah S , Peoples GE 
Published: December 2010

Abstract
Abstract #3139
Background: Our Cancer Vaccine Development Program has performed phase I and II clinical trials using immunogenic peptides from the HER2/neu protein. AE37 (aa:776-790+Ii-Key) is HLA promiscuous whereas E75 (aa:369-377) and GP2 (aa:654-662) are HLA-A2/A3+ restricted. The peptides are located on the intracellular, extracellular, and transmembrane portions of the HER2/neu protein. We evaluate patients who required dose reductions and compare them to those who did not in our three peptide vaccine trials to determine the immunologic and clinical relevance of different responses to the peptide vaccines. Methods: Three vaccine trials were performed separately with similar dose escalation design by varying the amount of AE37, GP2 or E75 peptide and GM-CSF adjuvant. Dose reductions (DR) were made in event of significant toxicity (&gt;100mm local or ≥grade 2 systemic) by decreasing GM-CSF (or peptide if no GM-CSF) by 50% for subsequent inoculations. We compared patients necessitating DR and those who did not. Immune response was measured ex vivo via 3H-thymidine proliferative assays or HLA-A2:Ig dimer assays and in vivo via DTH reactions pre- and post-vaccine. Recurrence and mortality data were available for E75 treated patients at 30-month median follow-up. Results: 132 patients underwent peptide vaccination and 39 patients required DR (Table 1).&#x2028; &#x2028; No patient had grade 3-5 local or systemic toxicities. DR patients, particularly those reduced for robust local reactions (DR-L), had greater immune responses ex vivo and in vivo. The post-vaccine DTH in DR-L patients compared to all other vaccinated patients was significantly larger in E75 (24.5±4.1mm vs. 12.7±1.3mm; p=0.001) and trended towards significant in AE37 (69.4±10.3mm vs. 35.8±14.9mm; p=0.08) and GP2 (48.9±14.1mm vs. 24.1±3.3mm; p=0.08). No recurrences or deaths were noted in the E75 DR patients; but for patients not requiring dose reductions there were 10 (12.5%) recurrences and 1 (1.25%) death.Discussion: All three peptide vaccines are safe and well-tolerated with minimal toxicity. The safety was partly due to reducing GM-CSF (or peptide if no GM-CSF) by 50% for patients with &gt;100mm local reactions or &gt;grade 2 systemic toxicity. DR patients, particularly DR-L patients, immunological responses were larger. This increased immune response (noted by DTH) suggests improved clinical response as there have been no recurrences or deaths among DR patients. Our analysis indicates that the optimal method of dosing HER2/neu peptide vaccines consists of constant peptide dose with a large enough dose of adjuvant to generate robust local reactions and that when local reactions are &gt;100mm performing DR of adjuvant by 50% for subsequent inoculations.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3139.
Correlation of tumor burden, liver and bone metastasis with serum extracellular domain HER2 expression in front-line metastatic breast cancer.
Authors: Johnston S , O'Rourke L , Wang W , Pegram M , Press MF , Maltzman J 
Published: December 2010

Abstract
Abstract #3146
Background: Although serum extracellular domain (sECD) HER2 levels can be easily measured by enzyme immunoassays, the potential clinical utility of HER2 extracellular domain protein shed in the serum is not established. High serum protein levels may be indicative of metastatic disease to the liver or perhaps greater tumor burden. EGF30008 is a double-blind, placebo-controlled phase III trial evaluating the effect of letrozole with/without lapatinib in previously untreated postmenopausal women with hormone receptor-positive metastatic breast cancer. Levels of sECD HER2 were collected on all 1,286 women at baseline and every 4 weeks on study including at disease progression.&#x2028; Methods: Baseline serum levels and tumor characteristics were collated in blinded fashion for all 1,286 patients in the trial (data cut off 12May08). Patients with baseline serum protein levels ≥ 15 ng/mL were defined as sECD HER2+. Correlations were assessed between baseline serum protein levels and baseline liver disease and bone-only disease and total tumor burden (as defined by number of metastatic sites). Chi-square test was applied to assess the correlation between serum protein levels and liver disease or bone-only disease. Wilcoxon rank-sum test using normal approximation was used to compare total tumor burden and baseline protein levels.&#x2028; Results: Among sECD HER2+ patients, 42% had at least one liver metastasis, whereas 20% of sECD HER2-negative patients had at least one liver metastasis (P &lt; 0.0001). No correlation exists between baseline serum protein level and bone-only disease (P = 0.64). Patients who were sECD HER2+ had a greater total tumor burden (mean metastatic sites = 5.4; standard deviation = 3.2; median = 5) compared with patients who were sECD HER2-negative (mean metastatic sites = 4.4; standard deviation = 3.1; and median = 4; P &lt; 0.0001).&#x2028; Conclusion: High baseline sECD HER2 strongly correlates with tumor burden. There was also a significant correlation between sECD and liver metastases, but no correlation at all with bone-only disease. These analyses will be repeated after the database is finalized and unblinded. Our analysis is limited to detection of the number of metastatic sites and is not sensitive to the individual sizes of metastases. In addition, another potential explanation for the low sensitivity of HER2 detection by sECD is that small metastatic deposits that are HER2+ in situ do not shed enough sECD into the serum to be detected by the assay. Conversely, some very large HER2-negative tumors do in fact shed measurable sECD if the tumor bulk is very high, even though in situ they may be nonamplified. A future analysis will take the sum of the longest diameters of all known lesions and compare it to sECD HER2 levels.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3146.
Baseline serum extracellular domain HER2 expression in hormone receptor-positive metastatic breast cancer: correlation with known tissue HER2 status.
Authors: Johnston S , O'Rouke L , Wang W , Pegram M , Press MF , Maltzman J 
Published: December 2010

Abstract
Abstract #3147
Background: The extracellular domain (ECD) of the HER2 protein is cleaved by metalloproteases and shed into the serum. Serum ECD (sECD) HER2 can be detected by ELISA and may have prognostic/predictive associations in patients (pts) with breast cancer. Although use of sECD HER2 as a surrogate for HER2 overexpression in hormone receptor-positive (HR+) metastatic breast cancer (MBC) is controversial, seroconversion can occur at disease relapse and may reflect a change in tumor HER2 status that is associated with a poorer prognosis. EGF30008 is a double-blind, placebo-controlled, first-line, phase III trial of letrozole with/without lapatinib in 1,286 postmenopausal women with HR+ MBC. We report baseline sECD HER2 at study entry on all pts and the association with original tumor HER2 status.&#x2028; Methods: Serum samples were collected at study entry and every 4 weeks on study, including at disease progression. Patients were defined as sECD HER2+ if baseline sECD HER2 was ≥15 ng/mL. HER2 status was evaluated in tumor tissue by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), using conventional cutoffs. To assess the correlation between baseline sECD HER2 and tumor tissue HER2 status, odds ratios (OR) with 95% confidence intervals (CI) and sensitivity/specificity (tumor tissue HER2 status as standard) were calculated. Data were from a blinded cutoff on 12May08. These analyses will be repeated after the database is finalized and unblinded.&#x2028; Results: Mean age was 63 ± 9.8 years. All pts had a HR+ original tumor, and 217 (17%) pts were confirmed as HER2+ by IHC or FISH. Median time from primary diagnosis to MBC was&#x2028; 3.3 years (range 0 - 33.9 yrs). Baseline sECD HER2 levels ranged from 2.5 to &gt; 560 ng/mL (mean 21 ± 60 ng/mL) with a bimodal distribution consistent with previously published data. The mean was 62 ng/mL (range 2.8 to &gt; 560 ng/mL) for HER2+ pts and 12 ng/mL (range 2.5 to 113.1 ng/mL) for HER2-negative pts. The OR between sECD HER2 at study entry and HER2 status of the original tumor was 4.5 (95% CI: 3.2, 6.2) with 42% sensitivity and 86% specificity.&#x2028; Conclusions: This OR suggests some correlation exists between baseline sECD HER2 and original tumor HER2 status. We cannot assess the rate of seroconversion that may have occurred from primary diagnosis until MBC at study entry. The bimodal distribution suggests that a clear cohort of pts exists at the time of relapse/study entry who are positive for sECD HER2. Analyses are evaluating whether subsequent changes in sECD HER2 levels occur over time during therapy, whether seroconversion predicts for a shorter time to relapse during letrozole monotherapy, and whether any differences exist in sECD HER2 levels over time for pts treated with letrozole plus lapatinib are ongoing.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3147.