bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-05-17: Correlation between cyclin D1, estrogen and progesterone receptors in invasive breast cancer after short-term treatment with tamoxifen or anastrozole
Authors: Millen EC , Mattar A , Logullo AF , Nonogaki S , Soares FA , Gebrim LH 
Published: August 2014

Abstract
INTRODUCTION: Hormone therapy is associated with reduced breast cancer mortality. The use of biomarkers that are predictive of early cellular responses has been explored as a predictor of hormone resistance. Estrogen and progesterone receptor positivity and cyclin D1 have been associated with resistance to treatment with tamoxifen.
OBJECTIVES: The aim of this study was to investigate the variations in the levels of cyclin D1 and the estrogen and progesterone receptors (ER and PR, respectively) in postmenopausal patients with ER− or PR-positive breast cancer after short-term treatment (26 days) with tamoxifen, anastrozole or a placebo.
METHODS: This was a prospective, randomized double-blind study conducted in 71 patients with infiltrating ductal carcinoma (stages II and III) receiving care at either Pérola Byington Hospital or São Paulo Hospital (São Paulo, Brazil). The patients were divided into three groups based on their treatment during the preoperative period (26 days): P (placebo, N = 26), T (tamoxifen, 20 mg/day, N = 22) and A (anastrozole, 1 mg/day, N = 23). The biopsies were performed at diagnosis and after mastectomy (26th day), and the tumors were isolated by tissue microarray. Immunohistochemistry was performed using anti-cyclin D1 (Novocastra DCS-6), anti-ER (Dako-M7047) and anti-PR (Dako-M3569) antibodies. The semiquantitative analyses were performed using Allred criteria, and the statistical analyses were performed with the ANOVA parametric test (p ≤ 0.05).
RESULTS: A reduction in the mean PR level from 4.22 (pre-treatment) to 1.94 (post-treatment) was observed only in patients treated with anastrozole (p = 0.01). A positive linear correlation between cyclin D1 and PR levels was observed in group A (p = 0.0001), whereas group T exhibited a negative correlation (p = 0.0001). No correlation was observed in group P (p = 0.35).
CONCLUSION: PR and cyclin D1 are likely predictive of an early response to aromatase inhibitors in breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-17.
Abstract P2-05-18: Deregulation of the Abl interactor 1 signaling as a potential biomarker for metastatic breast cancer.
Authors: Tang Hongxing , Lockman Paul , Tao Yunxia , Dai Zonghan 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-18.
Abstract P2-06-02: Genomic evolution from primary breast cancers to distant metastases
Authors: Hoefnagel LDC , Moelans CB , van der Groep P , van der Wall E , van Diest PJ 
Published: August 2014

Abstract
Purpose: Genomic evolution is an accepted concept during cancer development and progression. However, little is known about the changes that occur during the metastatic process despite the fact that breast cancer metastases are the leading cause of death in breast cancer patients. The purpose of this study was therefore to investigate whether distant breast cancer metastases show progression in copy number changes of onco- and tumor suppressor genes compared to their primary tumor.
Material and methods: Multiplex ligation-dependent probe amplification (MLPA) was used to compare copy number of 21 established oncogenes and tumor suppressor genes between primary breast cancer samples and corresponding distant metastases in 55 patients. Genes studied were ESR1, EGFR, FGFR1, ADAM 9, IKBKB, PRDM14, MTDH, MYC, CCND1, EMSY, CDH1, TRAF4, CPD, MED1, HER2, CDC6, TOP2A, MAPT, BIRC5, CCNE1 and AURKA.
Results: Overall, there was no significant difference in mean copy number between primary tumors (1.26 +/− 0.6) and metastases (1.27 +/− 0.64) (p = 0.826), but on the individual gene level, mean copy number for PRDM14 (p = 0,023), MED1 (p = 0.001) and CCNE1 (p = 0.039) were significantly higher while TRAF4 (p = 0.038) copy number was significantly lower in the metastases. Using dichotomized MLPA data, MTDH amplifications were significantly more frequent in the primary cancers compared to the metastases (27.3% vs.14.6%, p = 0.039), while significantly more CDH1 losses were found in the metastases compared to the primary tumor (23.6% vs. 9.1%, p = 0.039).
Conclusion: Distant breast cancer metastases show genomic evolution from the primary cancer as reflected by copy number changes in several established onco- and tumor suppressor genes.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-06-02.
Abstract P2-10-12: How well predict the 2011 St Gallen early breast cancer surrogate phenotypes metastatic survival?
Authors: Vanderstichele A , Brouckaert O , Tuyls S , Amant F , Leunen K , Smeets A , Berteloot P , Van Limbergen E , Weltens C , Peeters S , Moerman P , Floris G , Paridaens R , Wildiers H , Vergote I , Christiaens M-R , Van Calster B , Neven P 
Published: August 2014

Abstract
BACKGROUND: The five prognostic surrogate phenotypes, defined by the 2011 St Gallen consensus, predict metastatic relapse following early breast cancer treatment (Brouckaert et al Ann Oncol 2012). It is unknown to what extent these surrogate phenotypes defined on the primary tumor predict metastatic survival (MS) in a cohort of consecutive women with metachronous metastases.
PATIENTS & METHODS: All 4318 patients with primary operable breast cancer, diagnosed between 01–01-2000 and 31–12-2009 and treated in our center were prospectively entered in our institutional database. We included 345 patients with a (distant) metastatic relapse during their follow-up. We observed metastatic survival as the time between the diagnosis of the relapse and death. Tumor subtype was defined according to the 2011 St Gallen recommendations in 5 groups: luminal A (ER+/HER2−, grade 1–2), luminal B1 (ER+/HER2−, grade 3), luminal B2 or luminal-HER2 (ER+/HER2+), HER2-like (ER−/HER2−) and triple-negative. We focused on the value of the primary tumor subtype as a major prognostic determinant, but also assessed age at diagnosis, tumor size, lymph node involvement, tumor subtype, PR-status, primary detection (screening vs. palpation), histology, adjuvant therapy, distant-metastasis free interval (DMFI), first-line metastatic hormonal therapy, recurrence sites (isolate or multiple) and metastasis detection (clinical vs. biochemical).
RESULTS: In our cohort, we recorded a median metastatic survival (MS) of 22.3 months (95% CI: 19.7–25.6) and a 5-year survival probability of 15%. Significant differences in median MS were noted when considering the primary tumor subtype (cf. table).
We observed an independent prognostic effect for multiple recurrence sites (HR = 1.78, 95% CI 1.37–2.32), first-line metastatic hormonal therapy (HR = 0.30, 95% CI 0.18–0.49), DMFI (HR = 0.92 CI 0.85–0.98) and, finally, primary tumor subtype.

CONCLUSION: Our results showed that primary tumor subtype, DMFI, solitary recurrence and first-line metastatic hormonal therapy act as independent prognostic factors in metastatic breast cancer.
In order to overcome the biological complexity of metastatic breast cancer, we must appreciate the primary tumor subtype in our therapeutic approach.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-12.
Abstract P2-10-14: Triple Negative Breast Cancer: prognosis of triple-negative breast cancers and non-triple-negative breast cancers in a large registry of certified breast units
Authors: Kern P , Rezai M 
Published: August 2014

Abstract
Background: Prognosis of Triple-Negative Breast Cancer (TNBC) and non-TNBC has been evaluated predominantly in smaller subset of patients, and pooled analyses include various subsets of institutional standards.
The West German Breast Center includes more than 200 certified breast units covering approx. 65 % of all breast cancer cases in the country.
Material and Methods: We included all primary breast cancer cases of the last 3 years whenever patients received any kind of neoadjuvant or adjuvant chemotherapy in all certified breast units affiliated to the West German Breast Center.
Data was submitted in a computer-based registry, where standardized data is prospectively collected. Data monitoring and benchmarking is held 6-monthly which guarantees a high standard of performance.
Results: 34 675 non-TNBC patients achieved a DFS of 92,4 % at 2 years and 81,2 % at 3 years whereas out of 3728 TNBC-patients only 79 % were disease-free at 2 years and 57,4 % at 3 years.
With regards to overall survival 97,3 % of non-TNBC patients were alive at 2 years and 92,2 % at 3 years, whereas 89,3 % TNBC-patients were alive at 2 years and 82,9 % at 3 years.
Conclusion: In this large registry of certified breast units from the West German Breast Center we could underline the significant differences of prognosis as to DFS and OS between the non-TNBC and TNBC-subgroup of patients, displaying survival rates with modern 3rd generation chemotherapy, surgical treatment and radiotherapy in a controlled setting with prospectively collected data.
To is, to our best knowledge, one of the largest data sets ever exploring the differences in prognosis between TNBC and non-TNBC-patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-14.
Abstract P2-10-24: Independent validation of Recurrence Online using 1,638 breast cancer microarray samples
Authors: Györffy B , Weltz B , Benke Z , Timar J , Sztupinszki Z , Schaefer R 
Published: August 2014

Abstract
Background: RecurrenceOnline.com uses Affymetrix microarrays to compute the recurrence score and to measure estrogen receptor and HER2-receptor status for breast cancer patients. Our aim was to assess the efficacy of measuring HER2 status as well as the accuracy of survival prediction using an independent set of breast cancer gene expression profiles.
Methods: In GEO, we mined new datasets published after the release of Recurrence Online containing detailed clinical characteristics of the profiled cancer patients. The raw microarray data were downloaded and each array was analyzed by running the algorithm available at www.recurrenceonline.com. Then, the subgroups were compared using Kaplan-Meier analysis. For HER2 status determination, the immunohistochemistry (IHC)-based HER2 results were correlated to the microarray results. The cut-off value for HER2 mRNA positivity was set to 4,800. The accuracy was assessed using chi-square tests.
Results: Altogether 1,638 new breast cancer samples were analyzed in 9 GEO datasets (these include GSE16446, GSE17907, GSE19615, GSE25066, GSE20711, GSE26971, GSE31448, GSE31519, and GSE20685). The average relapse-free survival among these patients was 4.51 years, 68% of patients were ER positive and 672 were lymph node positive. RecurrenceOnline was capable to classify all patients into good and bad prognosis groups with high accuracy in all patients (p = 2.04E−09), and with p = 1.6E−03 after excluding lymph node positive samples. HER2 IHC data were published for 1,177 patients, with 12% of the patients being positive. HER2 status was correctly assessed for 93% (p &lt; 7E−20) of the patients.
Discussion. We verified the classification accuracy of RecurrenceOnline using independent datasets. Our results further support the feasibility of using genome-wide microarrays for patient classification.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-24.
Abstract P2-10-33: Mitotic Component of Grade Can Distinguish Breast Cancer Patients at Greatest Risk of Local Relapse
Authors: Done SJ , Miller NA , Wei Shi W , Pintilie M , McCready DR , Liu F-F , Fyles A 
Published: August 2014

Abstract
Background: With the recent recognition of many different molecular subtypes of breast cancer a desire to more specifically categorize tumors to allow tailoring of treatment to individual patients has developed. This has largely involved the development of molecular tests rather than the re-examination of current pathologic criteria. We wanted to evaluate standard pathologic features to determine their ability to predict for local recurrence.
Materials and Methods: Slides were retrieved for review from 280 of 769 women who had participated in a trial of tamoxifen with or without breast irradiation between December 1992 and June 2000 and for whom outcome data up to 18 years was available. All women were 50 years of age or older at the time of enrollment and had T1 or T2 node negative breast cancer. The cases for which slides were obtained were representative of the whole group. The slides were reviewed by two breast pathologists (SJD and NAM). Several features were evaluated; modified Nottingham histologic grade and its components- degree of tubule formation, nuclear pleomorphism and mitotic count. Mitotic component of grade was calibrated to the microscopic field size used. The presence of lymphatic/vascular space invasion was also scored. A statistical analysis was performed to relate these pathologic features to local recurrence at up to 18 years.
Results: The strongest predictor of local recurrence was the mitotic component of the Nottingham histologic grade with 5.7% for mitotic score 1/3 (n = 200), 19.6% for mitotic score 2/3 (n = 37) and 19.8% for mitotic score 3/3 (n = 43)(Gray's p-value = 0.0021). Overall grade was also able to predict for local recurrence with 2.6% for Grade 1 (n = 49), 10.6% for Grade 2 (n = 162) and 17.9% for Grade 3 (n = 71)(Gray's p-value=0.026). However, neither architecture (0% vs. 9.5% vs. 9.8%, Gray's p-value=0.74) nor degree of nuclear pleomorphism (0% vs. 7.9% vs. 11.5%, Gray's p-value=0.37), the other components of histologic grade, showed a statistically significant difference for recurrence. The presence or absence of endothelial lined space invasion was also found to be not statistically different (9.3% vs. 13%, Gray's p-value=0.55).
Conclusion: Within this cohort of tamoxifen treated T1 and T2 breast cancer patients 50 years of age or older, mitotic index could stratify women into groups with high and low risk of recurrence. If validated this may be a useful way of allocating patients to different treatment groups. Additional validation studies are planned on similar groups of patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-33.
Abstract P2-10-38: Prognostic factors uPA/PAI-1: measurement in core needle biopsies
Authors: Vetter M , Landstorfer B , Lantzsch T , Buchmann J , Große R , Ruschke K , Holzhausen H-J , Thomssen C , Kantelhardt E-J 
Published: August 2014

Abstract
Background: The urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 are validated as prognostic factors at the highest level of evidence within the node-negative group of breast cancer patients (Harris L et al., JCO 2007; 25:5287).
Usually, patients receive a core-needle biopsy before surgery. A prior feasibility study showed that the method of sampling (ex vivo from the surgical specimen using a small core needle or the larger excision specimen) doesn't influence the uPA and PAI-1 results (Thomssen et al., J Natl Cancer 2009; 101:1028). With the current study, we assessed how well uPA and PAI-1 values obtained from the core needle biopsy (in vivo) predict the expression level of these prognostic factors in the later surgical specimen.
Material and Methods: Fresh frozen material of 2–3 core needle biopsies (min 10 mg each) and the corresponding tumor material (min 50 mg) removed by subsequent surgery were collected from 110 patients in two hospitals. Only areas of the surgical specimen were selected for testing that had a sufficient distance to the needle biopsy defect. The uPA and PAI-1 concentrations were analysed using a commercially available ELISA test (FEMTELLE™; American Diagnostica, Inc., Stamford, CT). The predictive values (and sensitivity/specificity) of the core-needle biopsy data were calculated to forecast the uPA and PAI-1 values of the corresponding surgical specimen results.
Results: Sensitivity, specificity, the positive (ppv) and negative (npv) predictive values for uPA, PAI-1 and for the combination of uPA/PAI-1 are listed in table 1. Low concentrations of uPA in the core needle biopsies correlate with low concentrations in the surgical specimens across the entire study cohort as well as in the group with an intermediate (G2, N0) risk (npv = 0.91).
The clinical and pathological data of the cohort and the risk assessment will be presented.

Conclusion: Most important, low uPA/PAI-1 results in core-needle biopsies predict low results in the surgical specimen. In some cases, core-needle biopsies and surgical specimen show discordant data. These cases do not correlate with any clinical or pathological factors such as time between needling and surgery, grading, tumor size or hospital. We assume that these discordances are caused by pre-surgical manipulations, which change expression patterns in the remaining tissue as it is reported also from multi-gene tests.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-38.
Abstract P2-10-42: Gene expression profiling to predict the risk of locoregional recurrence in breast cancer
Authors: Drukker CA , Nijenhuis MV , Elias SG , Wesseling J , Russell NS , de Snoo F , van't Veer LJ , Beitsch PD , Rutgers EJT 
Published: August 2014

Abstract
Background The 70-gene signature (Mammaprint™) has been developed to predict the risk of distant metastases in breast cancer and select those patients who will have benefit in survival from adjuvant treatment. Aside from distant metastases, the development of locoregional recurrence is a significant predictor of survival. Given the strong association between locoregional recurrence and distant recurrence, we hypothesize that the 70-gene signature will be predictive of locoregional recurrence as well.
Methods We updated follow-up and radiotherapy details for all 1053 unique breast cancer patients treated at the NKI-AVL who previously participated in various 70-gene signature validation studies. Diagnosis was between 1984 and 2006. All patients were primarily treated surgically with either breast-conservation therapy or mastectomy. Adjuvant treatment consisted of radiotherapy, chemotherapy and/or endocrine therapy as indicated. Known risk factors for locoregional recurrence including age, tumor free resection margins, tumor size, grade, ER status, Her2 status, nodal irradiation and tumor bed boost were included in our analysis in addition to the 70-gene signature result.
Results Through 10 years of follow-up, 80 locoregional recurrences occurred. Patients with a 70-gene signature high risk result (n = 492) had a locoregional recurrence risk of 8.8% (95%CI: 6.3–11.3) at 5 years and 13.5 % (95%CI: 10.2–16.8) at 10 years, which was 2.6% (95%CI: 1.2–4.0) at 5 years and 5.7% (95%CI:3.5–7.9) at 10 years for patients with a low risk 70-gene signature (n = 561)(Logrank: p &lt; 0.0001). Accordingly, patients with a high risk 70-gene signature had an approximately 3 times higher risk of locoregional recurrence than patients with a low risk 70-gene signature (univariable hazard ratio (HR) 2.89; 95%CI: 1.80–4.63). Adding the 70-gene signature to a Cox proportional hazard model containing age, size, grade, ER status, involvement of axillary lymph nodes, surgical treatment and adjuvant treatment (radiotherapy, chemotherapy and/or endocrine therapy), significantly improved the model (likelihood ratio: p = 0.007). In that model, the multivariable HR for high versus low 70-gene signature risk was 2.27 (95%CI: 1.24–4.15).
Conclusion The 70-gene signature is able to predict the risk of locoregional recurrence, independent of known risk factors. Using the 70-gene signature may help in selecting those patients who will benefit from extensive adjuvant treatment. Additionally, the 70-gene signature may also select a group of patients at a low risk of locoregional recurrence who may be cured with limited local treatment alone.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-42.
Abstract P2-11-11: Patient Reported Outcomes after Breast Cancer Surgery and Adjuvant Therapy from a German Breast Cancer Centre
Authors: Feiten S , Dünnebacke J , Heymanns J , Köppler H , Thomalla J , van Roye C , Wey D , Weide R 
Published: August 2014

Abstract
Objectives: Evaluation of the subjectively experienced physical, psychological, social and job-related consequences of breast cancer.
Methods: Standardized paper pencil interview of patients with the initial diagnosis of breast cancer who had their primary surgery between 01/2006 and 12/2010 at an accredited breast cancer centre followed by systemic adjuvant treatment. The data collection was conducted with the help of a self-developed scanner-readable questionnaire which had been evaluated in a pretest.
Results: 1260 patients were contacted, 871 completed questionnaires (return rate 72%) were analyzed. Median age of the patients (99.5% women) at the time of the interview was 65 years (30–91). 6% relapsed during the observation period. 91% were “satisfied” or “very satisfied” with the surgical result. 67% indicated a complete freedom of pain. 23% received lymphatic drainage at the time of the questioning (11/2011), 33% complained about limitations of arm and/or shoulder function. 76% received anti-hormonal therapy, 13% stopped the anti-hormonal medication prematurely. Patients received a mean of 1.3 different anti-hormonal therapies, 54% took Tamoxifen. Psychological distress, cognitive limitations and physical consequences were rated on a scale from 1 – “not at all” to 4 – “very much”. The highest average values were found for the items sleep disturbances (2.3) and exhaustion (2.3), the lowest for depression (1.7) and word-finding difficulties (1.8). After therapy only 39% described a complete recovery of their physical capacity, 62% regained their previous mental capacity. 44% were in employment before their disease. 67% returned to their workplace but only 65% of them with their previous number of hours. 15% indicated disadvantages in their workplace due to the breast cancer disease. For 75% their partnership did not change, 12% experienced a deterioration, 13% an improvement. Before the illness 9% consulted a psychiatrist/psychotherapist, after the illness 18%. Before the diagnosis of breast cancer 13% received antipsychotic drugs, after the disease 25%.
Conclusions: Breast cancer diagnosis and therapy leads to long lasting impairment of physical, psychological, social and job-related functioning in a significant number of patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-11.