bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5-20-06: Survival in Women with Breast Cancer Who Used or Did Not Use Scalp Cooling in the Neoadjuvant/Adjuvant Setting.
Authors: Lemieux J , Perron L , Provencher L , Brisson J , Amireault C , Blanchette C , Maunsell E 
Published: June 2012

Abstract
Background
Scalp cooling can prevent chemotherapy-induced alopecia. Success varies according to the type of chemotherapy. A controversy exists regarding the use of scalp cooling because of the lack of safety data. No data are available regarding the impact on survival.
Purpose: To compare overall survival in women who used or did not use scalp cooling in the neoadjuvant/adjuvant setting.
Method: The survival of women treated in a specialized breast cancer centre (the Centre des Maladies du Sein Deschěnes-Fabia) in Quebec City who all used scalp cooling was compared to that of a population-based random sample of women treated in other regions of the province of Quebec (Canada) where scalp cooling is not available. Cox proportional hazard models were used.
Results: Overall, survival was comparable (and possibly better although not at a conventionally statistically significant level: HR = 0.80, 95 % CI: 0.63−1.01, p=0.06) among the 553 women who used scalp cooling compared to the 817 who did not. An interaction was found between scalp cooling and treatment in the adjuvant vs. neoadjuvant setting (p-interaction=0.015). In the adjuvant setting (n=485 scalp cooling and 740 no scalp cooling), the crude HR (in favour of scalp cooling) was 0.66 (95% CI: 0.50−0.87, p=0.003). In the neoadjuvant setting (n=68 scalp cooling and 77 no scalp cooling), the HR was 1.40 (95% CI: 0.84−2.33, p=0.2). No interaction was found with stage.
Conclusion: This is the first study to compare survival of women who used scalp cooling to that of women who did not. Scalp cooling to prevent chemotherapy-induced alopecia had no negative effect on survival in women with breast cancer who used it.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-06.
P5-20-07: Estimation of Febrile Neutropenia in Women Receiving Docetaxel Plus Cyclophosphamide as Adjuvant Therapy for Early Stage Breast Cancer: A Retrospective Analysis.
Authors: Bordoni RE , Haislip ST , Gilmore JW , Sharpe J , Abella E , Choi MR 
Published: June 2012

Abstract
Background: US Oncology Trial 9735 (Jones S, et al. JCO. 2006;24:5381–5387) established the docetaxel plus cyclophosphamide (TC) regimen as an effective adjuvant therapy for early stage breast cancer (ESBC). This trial did not specifically evaluate the incidence of febrile neutropenia (FN) as a study endpoint, but rates of 4%-8% were reported. Prophylactic granulocyte colony-stimulating factor (G-CSF) support was not allowed; reactive G-CSF support overall was not reported. Subsequent reports in the community setting have indicated FN rates of 25%-50% without G-CSF support and 0%-6.3% with G-CSF support (Table 1). To better determine the incidence of FN among ESBC patients treated with TC, we performed a retrospective clinical data review from the electronic medical record (EMR) database of Georgia Cancer Specialists, a large community oncology practice.
Methods: EMR data were captured between January 2006 and March 2010. Eligibility included women ≥ 18 years old with ESBC (stage I-IIIA) who completed ≥ 1 cycle of TC. The study time period was from the first dose of chemotherapy (CTX) to 6 weeks after the last dose of CTX, death, or loss to follow-up. The primary endpoint was the incidence of FN. Other endpoints included the incidence of severe (grade 3/4) neutropenia, neutropenia-related hospitalizations, G-CSF use, relative dose intensity (RDI), and dose delays and reductions. Results: Data from 662 patients were included in the analysis. Median age was 55 (range: 25–81) years. 40% of patients were white. The median number of CTX cycles received was 4 (range: 1–6). Most patients (91%) received G-CSF support; 73% as primary prophylaxis. See Table 2 for additional results.
Conclusions: This is the largest retrospective, community-based study to evaluate the incidence of FN in ESBC patients treated with TC. The observed FN rate of 5% (with 91% of patients receiving G-CSF) is consistent with other published reports using TC (Table 1). Our results suggest that TC is a taxane regimen with clinically significant myelosuppression (similar to other commonly used regimens in ESBC, such as TAC [NCCN Guidelines v2.2011]) and that the use of G-CSF support should always be considered.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-07.
PD03-02: Prognostic and Predictive Predictors for Triple Negative Breast Cancer.
Authors: Karn T , Pusztai L , Ruckhäberle E , Liedtke C , Schmidt M , Müller V , Gätje R , Hanker L , Ahr A , Holtrich U , Rody A , Kaufmann M 
Published: June 2012

Abstract
Background: Both the prognosis and the therapeutic options in triple negative breast cancer (TNBC) are rather limited. Current prognostic gene expression profiles for breast cancer mainly reflect proliferation status and are most useful in ER-positive cancers. The identification of prognostic gene signatures from TNBC cohorts in previous studies was hindered due to relatively small sample sizes.
Materials and Methods: All currently available TNBC gene expression datasets generated on Affymetrix U133 gene chips were assembled. To minimize inter-laboratory variation we analyzed only highly comparable arrays and data set-biased genes were filtered. Supervised analysis was applied to identify a prognostic signature from a finding cohort of 394 TNBC and validation was performed in an independent cohort of 261 TNBC. The genes from the prognostic predictor were analyzed for their correlation to known molecular phenotypes among TNBC.
Results: Two supervised prognostic signatures consisting of 264 and 26 probesets, respectively, were obtained when applying different cutoffs for false discovery rates of 25% and &lt; 3.5% in the finding cohort. In multivariate analysis in the independent validation cohort hazard ratios of 4.03 (95% CI 1.71−9.48; P=0.001) and 4.08 (95% CI 1.79−9.28; P=0.001), respectively, were obtained for the two signatures. When compared to 16 metagenes for previously described molecular phenotypes in TNBC the prognostic signatures displayed highest correlation to metagenes for IL-8/inflammation, VEGF/angiogenesis, and Histones. A subset of genes in the 264-probeset signature was inversely associated with a poor prognosis (29/264=11.0%). Most of these “good prognosis” genes are correlated with immune cell metagenes (21/29=72.4%). In contrast both identified supervised prognostic signatures did not correlate to previously published prognostic signatures (recurrence score, genomic grade index, Amsterdam signature, wound response signature, 7-gene immune response module, stroma derived prognostic predictor, and a medullary like signature). Regarding the response of TNBC to neoadjuvant chemotherapy the predictive value of the B-cell metagene was superior to the 264- and 26-probeset signatures. However combination of the B-cell metagene and the signatures increased the AUC in ROC-analysis from 0.606 to 0.656. Conclusions: The use datasets consisting only of TNBC allows identification supervised prognostic signatures for TNBC which are unrelated to previously known prognostic signatures.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD03-02.
PD05-01: Trans-CHER-Lob: A Biomarker Analysis of the Randomized Phase II Study of Neoadjuvant Chemotherapy Plus Trastuzumab, Lapatinib or Combined Trastuzumab and Lapatinib in HER2 Positive Operable Breast Cancer.
Authors: Guarneri V , Frassoldati A , Ficarra G , Maiorana A , Bettelli S , Bottini A , Cagossi K , Bisagni G , Ravaioli A , Amadori D , Musolino A , Cavanna L , Orlando L , Giardina G , Piacentini F , Bagnalasta M , Conte P 
Published: June 2012

Abstract
Introduction: The CHER-Lob study is a randomized phase II trial of preoperative sequential taxanes-anthracyclines in combination with trastuzumab, lapatinib, or combined trastuzumab and lapatinib in HER2 positive, stage II-IIIA breast cancer patients. A translational program to evaluate predictors of response as well as treatment effects on tissue biomarkers was pre-planned.
Methods: The CHER-Lob translational program includes the central evaluation of HER2, p95HER2, PTEN, pAKT, Ki67 on pre and post-therapy samples. All these biomarkers have been evaluated by immunohistochemistry. FISH analysis was performed in case of HER2 IHC 2+, and in all the discordant cases between central and local laboratories. Biomarkers change from baseline to surgery has been evaluated with the Wilcoxon signed-ranks matched-pair test.
Results: 121 patients have been randomized. The pathologic complete response rate (breast and axillary lymphnodes) was 26% in Arm A (chemotherapy + trastuzumab), 28% in arm B (chemotherapy + lapatinib) and 44% in arm C (chemotherapy + trastuzumab and lapatinib). The concordance between central and local HER2 assessment on pre-treatment biopsy was 97%.
The mean (min;max) PTEN expression pre- and post-therapy were 66% (0;100) and 68.4% (0;100) respectively.
The mean (min;max) pAKT expression pre- and post-therapy were 23.3% (0;100) and 8.8% (0;90) respectively. A significant decrease was observed in the overall samples (p=0.01). When analyzing the lapatinib alone arm, the difference was no longer significant (p=0.06), while it maintained significance when evaluating the two trastuzumab containing arms (p=0.0013). The mean (min;max) ki67 expression pre- and post-therapy were 29.5% (4;90) and 16.6% (1;50) respectively. A significant decrease was observed when looking at the whole population (p&lt;0.0001). A significantly higher ki67 inhibition was observed in the dual vs single anti-Her2 therapy (p= 0.003).
Conclusions: The central HER2 retesting showed a high concordance with local laboratories. Treatment induced a suppression in pAKT expression, that was higher in patients receiving trastuzumab. The dual anti-HER2 blockade induced a higher KI67 inhibition as compared to single anti-Her2 blockade. The evaluation of the predictive and prognostic role of these biomarkers is ongoing. Supported by GlaxoSmithKline
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-01.
PD05-03: Impact of Quantitative Measurement of HER2, HER3, HER4, EGFR, ER and PTEN Protein Expression on Benefit to Adjuvant Trastuzumab in Early-Stage HER2+ Breast Cancer Patients in NCCTG N9831.
Authors: Perez EA , Ballman KV , Reinholz MM , Dueck AC , Cheng H , Jenkins RB , McCullough AE , Chen B , Davidson NE , Martino S , Kaufman PA , Kutteh LA , Sledge GW , Geiger XJ , Ingle JN , Tenner KS , Harris LN , Gralow JR , Rimm DL 
Published: June 2012

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&lt;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.
PD05-07: Prospective Validation and Characterization of HER2 Positive Circulating Tumor Cells in Patients with HER2 Negative Metastatic Breast Cancer.
Authors: Olson EM , Flores LM , Najita JS , Curley C , Jeong J , Murray K , Savoie JJ , Winer EP , Krop IE 
Published: June 2012

Abstract
Background: Circulating tumor cells (CTCs) with evidence of HER2 amplification can occur in patients (pts) with clinically HER2 negative metastatic breast cancer. While these findings potentially have profound implications for CTCs as a biomarker for treatment, prospective validation and characterization of this subgroup is necessary.
Methods: We created a prospective cohort of pts with metastatic breast cancer that were HER2 negative by IHC and/or FISH on all available primary and metastatic biopsies. Blood samples were collected at study entry and then again at ≥ 3 weeks if available. CTCs were enumerated by a modification of the Veridex CellSearch Profile kit. FISH was performed on each CTC sample and reported as positive if the HER2/CEP17 ratio was ≥ 2.0. Analyses are descriptive.
Results: 66 pts were consented for study and this report includes the 65 pts with detectable CTCs. Median number of CTCs was 226 (range 112 to &gt; 3000). At initial testing, 23 pts (35%) had HER2 positive CTCs, median HER2:CEP17 ratio of 3.4. 50% (11 of 22) of the pts with lobular or ductal/lobular histology had HER2 amplified CTCs, compared to only 27% (10 of 36) of patients with ductal histology. Women with ER positive disease had HER2 positive CTCs in 40% of cases (20 of 49) compared to 19% of ER negative pts (3 of 16). To assess concordance of HER2 amplification of CTCs over time, 34 pts consented to be retested at a median 5.9 weeks after initial screening (range 3.3 - 17 weeks) and all but 1 had detectable CTCs. Baseline characteristics of these 34 pts were similar to the original population, with HER2 amplified CTCs detected in 35% (12 of 34) pts at initial screening. HER2 positive CTCs were concordant at time of retesting in 83% (10 of 12) pts; the 2 women with discordant CTCs were receiving HER2 directed therapy. Of the pts with HER2 negative CTCs at initial screening, 81% (17 of 21) continued to have HER2 negative CTCs at time of retesting.
Conclusion: We observed a higher prevalence of HER2 positive CTCs among pts with ER positive disease and evidence of lobular histology. The presence of HER2 positive CTCs is concordant over time in the majority of pts. The functional significance of HER2 positive CTCs in patients with clinically HER2 negative breast cancer will be tested in a prospective study with HER2−directed therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-07.
PD06-01: Molecular Classification with 21 Gene Assay (Oncotype DX®) Shows in 196,967 ER Positive Patients High Frequency of Low Recurrence Score [LRS] in Both Node Positive (N+) and Negative (N-) Breast Cancer (BrCa) Cohorts. Definition of Chemoresistance Based on LRS with Cost and Guideline Implications.
Authors: Ragaz J , Wilson KS , Wong H , Muraca G , Hryniuk W , Bajdik C 
Published: June 2012

Abstract
BACKGROUND : Key retrospective analyses have shown no benefit from adjuvant CT [CT] in ER+, N-ve and N+ve BrCa pts with LRS by Oncotype DX assay. (For N-ve, hazards [RR] = 1.31, 95% C.I.: 0.46, 3.78 (Paik et.al., 2006); for N+ve, RR=1.01, 95% C.I.: 0.54, 1.93 (Albain et.al. 2009)]. LRS (RS&lt;18) can therefore be equated to CT resistance (CTRES).
OBJECTIVES : 1. To determine the frequency of CTRES determined by Oncotype DX in the Genomic Health database of ER+, N-ve and N+ve pts. 2. To estimate the net cost savings resulting from avoidance of CT for CTRES pts, based on universal Oncotype DX testing in ER+ pts being considered for CT.
METHODOLOGY STEP 1 : Oncotype DX results were analyzed according to nodal status in the 196,967 ER+ tumor samples for CT candidates submitted to Genomic Health between Jan 2007 - Apr 2011.
STEP 2 : We then calculated the $ cost saved, result of Oncotype DX, assuming:
i. of new BrCa pts, 42% could be candidates Oncotype DX and CT (ER+, high risk N-ve; and all ER+ N+ve)
ii. either 50% or 100% CT avoidance — according to oncology practice — among LRS cases, estimating the CT cost/pt = $15,000 US; and Oncotype DX cost/pt = $4,000 US.
RESULTS — STEP 1 LRS based on Oncotype DX was more prevalent in N+ pts (chi sq p &lt;0.0001)

RESULTS — STEP2 ; CT Cost [in millions, USD] / 1,000 newly diagnosed cases who are CT and Oncotype DX condidates, of whom 50% [conservative estimates] will have LRS

Thus, in USA, with 225,000 new BrCa pts / year, and 94 500 [42%] candidates for Oncotype DX, over 47,250 pts will have LRS, with overall savings of $330.8 mil/year with 100% CT avoidance. In Canada, with 25,000 estimated new BrCa pts/year, corresponding savings will be $46.2 mil/year.
CONCLUSIONS:
1. Low RS status, presently the most reliable CTRES biomarker, is expressed with higher frequency among N+ve (59%) vs N-ve (54%) ER+ breast cancer pts.
2. If all eligible cases had the Oncotype DX test, and all with LRS would avoid CT, close to 50,000 pts in USA, and over 5,200 in Canada will be spared ineffective CT and associated toxicity / year, with hundreds of million dollars saved each year.
3. On principles of ethics and economy, these data suggest that until new research refines the molecular classification of BrCa for higher efficacy, and with lower cost and more practical access:
a. universal OncotypeDx testing for pts should be performed for all ER+ breast cancer pts candidates for CT;
b. management guidelines should be changed to avoid CT in all LRS pts, irrespective of nodal status;
c. until prospective randomized trials confirm CT benefit among LRS pts, its use should be considered investigational.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD06-01.
PD08-06: ERK2 Promotes Stem Cell-Like Characteristics in Triple-Negative Breast Cancer.
Authors: Bartholomeusz C , Saso H , Dadbin A , Kazuharu K , Hortobagyi GN 
Published: June 2012

Abstract
Background: Triple-negative breast cancer (TNBC) is resistant to targeted therapies such as hormonal therapy and HER2−targeted therapies. Thus, no specific targeted therapy is currently available for TNBC. ERK2, a component of the MAPK pathway, plays an important role in epithelial-mesenchymal transition (EMT) in MCF-7-10A, a nontransformed human mammary epithelial cell line and is required for full acquisition of stem cell-like characteristics. Inhibition of ERK2 dramatically reduces cell growth, whereas inhibition of ERK1 significantly facilitates proliferation. ERK1 mutant mice have a strikingly milder phenotype than ERK2 mutant mice, which die early in development. In addition, we have shown that the upstream target of ERK, MEK, may be a target for treating TNBC with the MEK inhibitor selumetinib. Our reverse-phase protein array analysis showed that of patients with TNBC, those with ERK2-overexpressing tumors were at higher risk of death than those with low-ERK2-expressing tumors. Therefore, we hypothesized that ERK2 promotes the tumorigenesis and metastasis of TNBC. We sought to determine the role of ERK2 in the tumorigenic and metastatic activities in TNBC and whether ERK2 is required for acquisition of stem cell-like characteristics in TNBC.
Methods: We studied the role of ERK1 and ERK2 in the TNBC cell line SUM-149. We used shRNA to specifically knockdown ERK1 and ERK2 (shERK1 and shERK2) and examined whether knocking down ERK1 and ERK2 correlated with EMT regulation, migration, and tumorigenicity in TNBC cells.
Results: Compared with parental SUM-149 cells, stable clones that constitutively expressed shERK1 or shERK2 showed no difference in growth rate. However, knocking down ERK2 significantly inhibited migration and the acquisition of stem cell-like characteristics (CD44+/CD24-) in SUM-149 cells in vitro. In addition, knockdown of ERK2 also inhibited anchorage-independent growth, an indicator of in vivo tumorigenicity, whereas knockdown of ERK1 did not inhibit anchorage-independent growth. However, inhibition of ERK1 or ERK2 in 2D or 3D cell culture did not correlate with changes in epithelial and mesenchymal markers by western blot analysis. Conclusion: Our data demonstrate that ERK2 may promote the tumorigenesis of TNBC via enriching cancer stem cells. Our long-term goal is to develop ERK-targeted therapy for TNBC.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD08-06.