bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1-06-25: Changes in FDG PET SUV Correlates with Ki-67 Following 2 Weeks of Aromatase Inhibitor Therapy in ER+ Early Stage Breast Cancer, a Pilot Imaging Study.
Authors: Gadi VK , Kurland BF , Specht JM , Rodler E , Korde LA , Peterson LM , Schubert EK , Chai X , Mankoff DA , Linden HM 
Published: June 2012

Abstract
Background: In estrogen receptor positive (ER+) tumors, a low proliferative index (Ki-67) two weeks into endocrine therapy predicts response. FDG PET non-invasively measures tumor sites in vivo. The pre-operative window is an opportunity to assess impact of systemic therapies. We tested associations between FDG PET standardized uptake value (SUV) and Ki-67 after two weeks of aromatase inhibitor (AI) therapy in newly diagnosed, postmenopausal women.
Methods: Postmenopausal patients with clinical stage I-II ER+ HER2− primary tumors underwent a 9–35 day “run-in” of AI monotherapy prior to definitive surgery. FDG PET was performed before AI therapy, and 1–5 days before surgery. Ki-67 was measured in baseline core biopsy and surgical specimens.
Results: To date, 18 patients (median age 59) have been enrolled of whom 14 patients have undergone serial FDG PET imaging with 12 completed assessment of Ki-67 in surgical samples including one who had no residual invasive carcinoma. The majority harbored ductal carcinomas (n=16) with 10/18 having histologic grade ≥ 2. The median number of days exposed to AI was 18 (range, 9–35). Baseline SUV ranged from 1.8 to 10.9 (median 2.5), and post run-in SUV (7-34 days later) ranged from 1.0 to 10.7 (median 2.5). A median 14% decrease in SUV was observed between paired FDG PET studies (range, 44% decline to 13% increase). Five of 12 patients’ index lesion FDG SUV declined by 20% or more; all also had Ki-67 ≤5% at surgery. An additional 5 patients with Ki-67 ≤5% at surgery had percentage change in FDG PET SUV of 0% to 17% decline. Results will be updated as accrual is ongoing.
Conclusions: Substantial changes in FDG PET SUV in the breast tumor were appreciated early in AI therapy. SUV declined or was stable in all but one patient of 14, and all patients with ≥ 20% decrease in SUV had a low (≤5%) Ki-67 at surgery. Serial PET is a promising measure of early response to therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-25.
P1-07-07: Assessing Two Methods of Meta-Analysis in Studies of Patients with Breast Cancer: Individual Patient Data-Based (IPD) Versus Literature Based Abstracted Data (AD) in 5 Meta-Analyses Including over 28,000 Patients. Are There Results Differences of Concern?
Authors: Gralla RJ , Bria E , Raftopoulos H , Sperduti I , Giannarelli D , Cognetti F 
Published: June 2012

Abstract
Background: Meta-analyses are widely used to provide high level evidence to resolve controversies. Differences of opinion continue concerning the two most frequently used methods (IPD and AD) and their roles in providing reliable recommendations for Evidence-Based Medicine. Some regard the IDP method as being more accurate, yet it is time-consuming, expensive, and can be troubled by getting data from all investigators. We tested whether overall conclusions would differ between the two methods when using the same studies for comparison. To overcome limitations related to simple correlation analysis, and: 1) to weigh the agreement between these 2 approaches (Bland-Altman [BA], Lancet 1986), and 2) to evaluate the eventual predictive role of the data coming from AD over IPD, an analysis with multiple methods was performed.
Methods: 5 meta-analyses in breast cancer examining 9 outcomes which had been subjected to IPD meta-analysis were selected. Literature-based AD meta-analyses were then conducted. Hazard Ratios (HR) and Risk Ratios (RRs) with 95% confidence intervals (CI) were extracted or derived from original meta-analyses. At least 90% of patients’ reports were required for the IDP analysis. Methods agreement was analyzed according to the BA method, as difference or ratios, and a comparison with the Variance-Ratio test (F-test), and the Concordance Correlation Coefficient (CCC) was done. Correlations between IPD/AD-ratios were estimated using a linear regression model with Pearson (r) and R2 coefficients (parametric) and Spearman's Rho/Kendall's Tau coefficient (non-parametric), to derive a predictive estimation on IPD when adopting AD. MedCalc® Software was used.
Results: 9 outcomes in 5 meta-analyses (28,358 patients) were analyzed, as seen in the table.

Graphical comparison between the deviation from the ‘line of identity’ identified with the B-A method did not show meaningful differences between AD and IPD (mean difference −0.01535, 95% CI −0.0315, 0.0008; mean ratio 0.9816, 95% CI 0.9625, 1.0008). No significant difference in the Variance (F-test 1.01, p=0.98), and a high concordance (CCC 0.9775, 95% CI 0.91, 0.99) were found. A highly significant correlation by both parametric and non-parametric tests allowed derivation of a linear regression equation able to predict estimation IPD results from AD data; R2 0.97, p&lt;0.001.
Conclusions: When analyzing the results of studies (AD) or patient results from those same studies (IDP) we found: 1) No significant or meaningful differences between the 2 meta-analysis methods; and 2) Data from the AD analyses are able to predict those from IPD, without significant risk of overestimation.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-07.
P1-07-12: Assessment of Real World HER2 Status by Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) in Breast Cancers: Comparison with HERmark®, a Validated Quantitative Measure of HER2 Protein Expression.
Authors: Huang W , Paquet A , Sivaraman S , Pesano R , Goodman L , Sherwood T , Lie Y , Hickey J , Walworth C , Haddad M , Anderson S , Bates M , Weidler J 
Published: June 2012

Abstract
Background: Accurate assessment of the HER2 status is critical in determining appropriate therapy for patients with invasive breast cancer. ASCO/CAP HER2 testing guidelines caution that up to 20% of routine HER2 testing by IHC/FISH may be unreliable (Wolff et al. JCO 2007;25:118). The HERmark assay is a novel quantitative HER2 protein measurement for determining HER2 status in breast cancer. Central HER2 testing showed high concordance (96-98%) with HERmark for positive and negative categories when equivocal subsets were excluded (Huang et al. Am J Clin Pathol 2010;134:303; Joensuu et al, 2008 SABCS, abstract 2071). In this study, we examined concordance between HERmark and routine HER2 testing by IHC and FISH from “real world” formalin-fixed, paraffin-embedded (FFPE) breast cancers submitted commercially for HERmark testing.
Methods: 717 HERmark results on FFPE breast cancers tested from 2008 to 2010 and corresponding HER2 IHC/FISH results were reviewed. The IHC and FISH results, per pathology reports submitted at the time of HERmark testing, were compared to HERmark categorical (negative, equivocal, positive) results.
Results: 590 (419) samples had IHC (FISH) and HERmark results available. Of these cases, 92% (94%) were either negative or equivocal by IHC (FISH). The HERmark testing reported 33% HERmark negative, 33% HERmark equivocal and 34% HERmark positive. Comparisons of HER2 status by IHC and FISH vs. HERmark are detailed in Table 1.

19% of cases classified as IHC 0 or 1+ were positive by HERmark; 35% classified as FISH negative were HERmark positive. Of the 158 triple negative cases by IHC/FISH (ER, PR and HER2 negative, data not shown), 38 (24%) were reclassified as HER2 positive by HERmark.
Conclusions: Higher than expected discordance between HER2 IHC/FISH and the HERmark assay was observed in this study compared with central HER2 testing of prior study cohorts. Selection bias may have impacted these results as ≥ 92% of cases submitted for HERmark testing were either equivocal or negative by routine HER2 IHC/FISH.
Central HER2 FISH retesting of these samples will be performed and compared with HERmark results to further evaluate the discordance observed in this analysis.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-12.
P1-07-18: Expanding an Online Tool for Genome-Wide Validation of Survival-Associated Biomarkers in Breast and Ovarian Cancer Using Microarray Data of 3,862 Patients.
Authors: Gyorffy B , Lanczky A , Szallasi Z 
Published: June 2012

Abstract
The pre-clinical validation of prognostic gene candidates in large independent patient cohorts is a pre-requisite for the development of robust biomarkers. We earlier implemented an online tool to assess the prognostic or predictive value of the expression levels of all microarray quantified genes in breast cancer patients. In present study, we further expanded our database, added additional analytical options and implemented the tool for ovarian cancer patients.
The database was set up using gene expression data and survival information of breast and ovarian cancer patients downloaded from GEO and TCGA (Affymetrix HGU133A, HGU133A 2.0 and HGU133+2 microarrays). After quality control and normalization only probes present on all three Affymetrix platforms were retained (n=22,277). Patients can be stratified into the various robust subtypes either by histology or by various gene expression profiling based methods. To analyze the prognostic value of the selected gene in the various cohorts the patients are divided into two groups according to the median expression of the gene. A Kaplan-Meier survival plot is generated and significance is computed.
All together 2,472 breast cancer patients and 1,390 ovarian cancer patients were entered into the database. These groups can be compared using relapse free survival (n=2,414 in breast cancer and 1,090 in ovarian cancer) or overall survival (n=463 and n=1,290). Follow-up threshold has been implemented to exclude long-term effects. The combination of several probe sets can be employed to assess the mean of their expression as a multigene predictor of survival and therapy efficiency.
In summary, we expanded our global online biomarker validation platform to mine all available microarray data to assess the prognostic power of 22,277 genes in 2,472 breast and 1,390 ovarian cancer patients. The tool can be accessed online at: www.kmplot.com/breast and www.kmplot.com/dev/ovar.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-18.
P1-07-20: Consistent High False Negative Rate of HER2 qRT-PCR of Oncotype DX® in Comparison to ASCO/CAP Recommended Combined IHC/FISH Method.
Authors: Dabbs DJ , Bhargava R 
Published: June 2012

Abstract
Background In our prior multi-institutional study of 843 cases we have shown a high false negative rate for HER2 testing by the oncotype DX® RT-PCR method, (ODX) compared to our combined FISH and IHC approach [J Clin Oncol 29: 2011 (suppl; abstr 603)]. This study is part of an ongoing quality assurance study, comparing HER2 test results by FISH/IHC and the ODX.
Methods From July 2010 till April, 2011, all patients who had either positive or equivocal HER2 results (on core biopsy) at Magee-Womens Hospital (MWH) by combined IHC/FISH, and who also had the ODX ordered (on resection specimen) by an oncologist, were reviewed for positive concordance of HER2 results. All tissues were fixed and FISH/IHC was reported according to ASCO/CAP HER2 guidelines. The core biopsy HER2 positive results were also confirmed positive on the same tissue block that was tested by ODX.
Results Of the total 234 cases, there were 21 cases that were either classified as positive (n=8) or equivocal (n=13) by combined IHC/FISH approach at MWH. Of the 8 MWH+ cases, 4 showed 3+ IHC score and these were also positive by ODX. The remainder 4 MWH+ cases were IHC 2+, and unequivocally amplified by FISH. These 4 cases were either equivocal (2 cases) or negative (2 cases) by ODX. Thirteen cases reported as equivocal by MWH FISH, were all reported as negative by ODX. Of the 213 MWH negative cases, 212 were also negative by ODX (percent negative agreement of &gt;99%) and one case was called equivocal. If all equivocal cases are excluded, then percent positive agreement (PPA) between IHC/FISH and ODX is 67% (4/6). If “equivocal” cases are considered as “negative”, then PPA is 50% (4/8). If “equivocal” cases are considered as “positive”, then PPA is only 29% (6/21).
Conclusions (1) Similar to our prior study [J Clin Oncol 29: 2011 (suppl; abstr 603)], there is a consistent poor percent positive agreement for HER2 testing between FDA cleared FISH/IHC methods and ODX, and these results cast serious doubt on the robustness/reliability of ODX results for HER2. (2) There should be serious concern raised over the reliability of the other multivariate index platform results of ODX, and likely, the ODX recurrence score for an individual patient, as this sensitivity data suggests inadequate tissue microdissection, or issues with the ODX test platform. (3) Clinicians need to be aware that HER2 results of ODX are not reliable for patients who are equivocal or amplified by FDA approved methods, and only FDA approved methods should guide treatment decisions.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-20.
P1-07-22: A Venezuelan Study of Breast Cancer Estrogen Receptor, Progesterone Receptor and HER2 Receptor Expression by the Standard Method, Immunohistochemistry (IHC), Compared to a New Method, Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR).
Authors: Marin C-EM , Ramirez AC , Baehner FL , Yoshizawa C , Acosta MM 
Published: June 2012

Abstract
Background: Assessment of ER, PR and HER2 is of significant importance in breast cancer diagnosis and treatment. We have performed the first large assessment of central IHC for ER, PR and HER2 by a South American (Caracas, Venezuela) Central Lab to Central Lab RT-PCR by Oncotype DX®.
Design: Breast cancer specimens from the Fundación BADAN were evaluated by IHC for ER (clone 1D5), PR (clone 636) using 1% staining for positivity using ASCO/CAP guidelines and HER2 (clone A0485) using ASCO/CAP guidelines of 3+ in ≥30%. Standardized quantitative RT-PCR analysis for ER and PR used Oncotype DX with the pre-defined cutoffs of 6.5 units and 5.5 units for positivity, respectively. For HER2 the standard pre-defined cutoffs were used: positive ≥11.5 units, equivocal &gt;10.7-&lt;11.5 units, and negative ≥10.7 units. For HER2 concordance analysis the equivocal range was excluded from both assays according to ASCO/CAP Guidelines (Wolff et al, 2006). For all quantitative RT-PCR assessments the reference normalized expression measurements ranged from 0 to 15, where each 1-unit increase reflects about a 2-fold increase in RNA.
Result: Evaluable data was obtained in 96 pts for ER, 95 pts for PR (1 patient assessment unavailable) and 89 pts for HER2 (7 patient assessments unavailable). Two-by-two tables (below) compare IHC versus RT-PCR for ER, PR and HER2. The overall concordance for ER between IHC and RT-PCR was 94% (Kappa 0.467; 95% CI 0.107, 0.828); for PR between IHC and RT-PCR was 92% (Kappa 0.668; 95% CI 0.457, 0.878); and for HER2 between IHC and RT-PCR was 97% (Kappa = 0.649; 95% CI 0.280, 1.000). Three IHC 2+ cases and 4 equivocal cases by Oncotype DX were excluded from Concordance and Kappa statistics.
Conclusion: RT-PCR by Oncotype DX for ER, PR and HER2 status is useful for active monitoring of IHC assays as mandated by ASCO/CAP guidelines. There is a high degree of overall concordance between central IHC performed in South America (Caracas, Venezuela) and central RT-PCR for ER, PR and HER2 status.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-22.
P1-08-03: Huge Improvement in Relapse-Free Breast Cancer Survival over the Last 25 Years.
Authors: Geurts SME , van Dijck JAAM , de Vegt F , Paquay Y , Siesling S , Verbeek ALM , Tjan-Heijnen VCG 
Published: June 2012

Abstract
Introduction The purpose of this study was to evaluate the dwindling risk of relapse in breast cancer patients treated with curative intent since the 1970s.
Patients and methods 8570 women diagnosed with invasive breast cancer in 2003 or 2004 were compared with 307 consecutively diagnosed patients with invasive breast cancer between 1972 and 1986 in the Netherlands. Five-year overall survival and 5-year risk of relapse, i.e. second primary breast cancer, locoregional recurrence or distant metastasis, were calculated using the Kaplan-Meier method. Multivariable Cox-proportional hazards modelling was applied to correct the period-specific risk of relapse for tumour size, lymph node involvement and age at diagnosis.
Results Median (range) age at diagnosis was 52 years (27-82 years) in 1972–1986 and 58 years (20-96 years) in 2003–2004. Patients diagnosed in 1972–1986 had a larger tumour size and similar nodal involvement as compared to patients diagnosed in 2003–2004. In 2003–2004 more women were treated with breast conserving surgery, chemotherapy, and hormonal therapy as compared to 1972–1986. The 5-year overall survival rate increased from 71% (95% CI: 65% — 76%) in the period 1972–1986 to 85% (95% CI: 84% — 85%) in the years 2003–2004. Five-year risk of any relapse decreased from 37% to 16% across the calendar years (table 1). This decrease was observed for the risk of locoregional recurrence and the risk of distant metastasis (table 1). Risk of second primary breast cancer was similar for both periods of diagnosis (table 1). After adjustment for tumour size, nodal status and age at diagnosis the decrease in risk of relapse remained significant for patients diagnosed in 2003–2004 compared to 1972–1986 (HR= 0.5, 95% CI: 0.4 - 0.6).
Conclusion Over the last decades, the risk of breast cancer relapse has tremendously decreased, also after adjustment for tumour stage and age at diagnosis. The improved prognosis can be explained by the more often administered and intensified systemic treatment procedures and, further, by an earlier detection. The similar nodal stage probably resulted from stage migration caused by a more thoroughly performed lymph node staging in 2003–2004 compared to 1972–1986.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-03.
P1-08-04: Obesity, Adjuvant Therapy, and Survival Outcomes in Early-Stage Breast Cancer.
Authors: Jiralerspong S , Wang T , Rimawi MF , Nangia JR , Schiff R , Giordano SH , Pollak MN , Chenault CC , Osborne CK , Hilsenbeck SG 
Published: June 2012

Abstract
BACKGROUND: Obesity has risen to epidemic proportions and is associated with worse breast cancer (BC) prognosis in most studies. However, the effects of obesity according to adjuvant therapy choice are largely unknown. To address this issue, we examined the relationship between body mass index (BMI), adjuvant therapy, and survival outcomes in a large cohort of early-stage BC patients.
METHODS: We retrospectively studied patients from the Baylor Breast Center Tumor Bank treated from 1970–1995. Patients were divided into 3 BMI classes: normal/underweight (N, BMI&lt;25), overweight (Ov, BMI 25–30), obese (Ob, BMI≥30); and 4 treatment groups: no adjuvant therapy, chemotherapy (mainly CMF), endocrine therapy (mainly tamoxifen), both chemo- and endocrine therapy. Time-to-recurrence (TTR), disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups via the log-rank test. Multivariate analysis was conducted via Cox proportional hazards models.
RESULTS: There were 4,368 patients. Median age was 58. 74% were postmenopausal. 72% had stage I-II disease, 28% stage III. 76% were estrogen receptor (ER)-positive, 24% ER-negative. Patients distributed into BMI classes as follows: N 48%, Ov 30%, Ob 22%. Higher BMI was associated with postmenopausal status and increasing age, tumor size, positive lymph nodes, and stage, as well as a higher likelihood of receiving treatment. Median follow-up was 5 years. Kaplan-Meier analysis showed that TTR was significantly shorter in the Ov and Ob groups as compared to the N group (p=0.019), due to distant (p=0.001) rather than local (p=0.970) recurrences. DFS was also significantly worse in the Ov and Ob groups (p=0.002), as was OS (p=0.001). The Table shows the hazard ratios for the various survival outcomes after adjustment for age, tumor size, nodal status, and treatment groups. For all patients, TTR, DFS, and OS were significantly worse in the Ob vs. N groups. TTR and DFS were significantly worse in the chemo treated Ob vs. N groups. DFS and OS were significantly better in the endo treated Ov vs. N groups.
DISCUSSION: In this large cohort of BC patients, survival outcomes (TTR, DFS, OS) were significantly worse in the obese group. This remained true after adjustment for multiple factors. Obesity was associated with worse survival outcomes in the chemo treated (CMF) group. Overweight was associated with better survival outcomes in the endo treated (tamoxifen) group. These results confirm and extend the results of previous studies. Further studies to discover the reasons for these differences in outcomes are underway.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-04.
P1-08-06: Breast Cancer among Patients with Diabetes, Obesity and Abnormal Blood Lipids – A Population-Based Register Study in Sweden.
Authors: Olsson H , Attner B , Landin Olsson M , Lithman T , Noreen D 
Published: June 2012

Abstract
Objective: To study how the incidence of breast cancer is related to diabetes, obesity or abnormal blood lipids.
Methods: Diagnosis of diabetes, obesity or abnormal blood lipids was studied 0–10 years prior to the diagnosis of cancer in 2724 cases of cancer and in 20542 controls matched regarding age, sex and domicile in a population based material. Diagnoses were obtained by using out and inpatient population based registries. Also the use of glargine and metformin was studied in relation to cancer risk in diabetic patients using the national pharmacy prescription registry. Conditional logistic regression was used for the analyses.
Results: Diabetes was significantly more common prior to diagnosis in patients with breast cancer with diabetes diagnosed 0–4 years prior to the cancer diagnosis. The findings remained after adjusting for obesity and high blood lipids. Obesity was significantly more common in patients with breast cancer above the age of 60 years in those where obesity was diagnosed close to the diagnosis of cancer. High blood lipids were significantly less common in patients with breast cancer close to diagnosis.
Glargine use was associated with a doubled risk 2.88 (1.15−6.64) and metformin use with a lower risk of cancer in diabetic patients 0.92 (0.82−1.09).

Conclusions: Within 4 years of diagnosis diabetes, obesity after age 60 and low blood lipids are associated with breast cancer. Glargine use seems to increase overall cancer risk.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-06.