bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-06-19: Impact of hospital surgical volume on breast cancer mortality: A population based study in the Netherlands
Authors: Siesling S , Tjan-Heijnen VCG , de Roos M , Snel YEM , van Dalen T , Wouters MW , Struikmans H , Maduro JH , van der Hoeven KJM , Visser O 
Published: August 2014

Abstract
Background: For some low-volume tumour types hospital surgical volume is associated with better survival. For breast cancer there is still much debate. The aim of this study is to determine to what extent the yearly surgical hospital volume determines the mortality in invasive non-metastatic breast cancer patients.
Method: Women diagnosed with primary invasive breast cancer in the period 2001-2005 were selected from the Netherlands Cancer Registry. Hospitals were grouped by their annual volume of surgery for invasive breast cancer. Cox proportional hazard models were performed including all patients with primary non-metastatic breast cancer who underwent breast surgery. Gender, age at diagnosis, morphology, grade, size (pT), number of positive lymph nodes, year of diagnosis and socio economic status (SES) were included as covariates. Follow-up was complete until the 1th of February 2013.
Results: In total 58.982 patients with invasive non-metastatic breast cancer were diagnosed during the period 2001-2005. Hospitals were grouped by volume of surgery: less than 75 (n = 19), 76-100 (n = 30), 101-150 (n = 29), 150-199 (n = 9) and 200 or more (n = 14) surgeries per year. Non-metastatic patients had a 8% higher risk of death in a low volume hospitals than a hospital with &gt;200 surgeries per year (HR 1.08, 95%CI 1.02-1.14).
Cox regression multivariable analyses: the relation of the number of surgical treated invasive breast cancer per hospital per year and the mortality of patients with non-metastatic breast cancer in the Netherlands, 2001-2005Variable HR95%CINumber of operated invasive breast cancers per yearmore than 200reference 150-1991.030.98-1.09 100-1491.010.97-1.05 75-991.040.99-1.08 less than 751.081.02-1.14Corrected for age, gender, morphology, grade, pT, number of positive lymph nodes, year of diagnosis, socioeconomic status
Patient and tumour characteristics like age (HR 1.05, 95%CI 1.05-1.05) and SES (lowest vs highest; HR 1.12, 95%CI 1.07-1.16), grade (low vs high, HR 1.72, 95%CI 1.63-1.82), tumour size (1-2 cm vs 2-5 cm; HR 1.46, 95%CI 1.40-1.51), and a higher number of positive lymph nodes (0 vs 1-3; HR 1.40, 95%CI 1.34-1.46 and 0 vs &gt;10; HR 3.19, 95%CI 3.00-3.39) influenced death to a larger extend than surgical volume.
Conclusion: In the Netherlands, surgical hospital volume influences risk of death marginally, and far less than patient and tumour characteristics. No differences in mortality between hospitals with a surgical volume of more than 75 were revealed for invasive non-metastatic breast cancer patients compared to hospitals with more than 200 operations. Over the more recent period of 2007-2012, only 3 hospitals had less than 75 operations on average per year, resulting in an even more comparable mortality between hospitals in future.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-19.
Abstract P6-06-25: Usefulness of pretreatment NLR as prognostic factor of late recurrence, 5-year after primary treatment
Authors: Noh H , Lee J , Choi E , Han A 
Published: August 2014

Abstract
Background
Prognostic factor and predictive factors are well established in early-stage breast cancer, but less is known about recurrence, especially 5-year after primary treatment. While mortality of breast cancer is from organic dysfunction with metastatic disease, not from the diseased breast itself, still we do not have adequate information about metastatic disease as we do about primary breast cancer itself.
The aim of this study is to investigate of usefulness of pretreatment NLR(neutrophil to lymphocyte ratio) as prognostic factor that can tell risk of recurrence 5- year after primary treatment.
Patients and methods
A retrospective review of invasive breast cancer patients surgically resected between January 2001 and December 2007. Exclusion criteria were as followings: patients with recurrence or death within 5yrs.
Results
A total of 301 patients were included and 13 patients experienced with recurrence after 5 years.
Table 1. Patients' characteristics Total (n = 301) N (%)Age*48.8(±11.4)Age ≤3525(8.3)35&lt; ≤50165(54.8)50&lt;111(36.9)Histology Ductal270(89.7)Lobular7(2.3)Others24(8.0)Tumor size (cm)*2.73(±1.64)T stage T1126(41.9)T2158(52.5)T317(5.6)N stage N0199(66.1)N167(22.3)N220(6.6)N311(3.7)unknown4(1.3)Histologic grade I72(23.9)II110(36.5)III70 (23.3)unknown49(16.3)Estrogen receptor Negative111(36.9)Positive185(61.5)unknown5(1.6)Progesterone receptor Negative129(42.9)Positive167(55.5)Unknown5(1.6)HER-2 Negative196(65.1)Positive98(32.6)unknown7(2.3)Molecular subtype Luminal A136(45.2)Luminal B66(21.9)HER-2 enriched32(10.6)Triple negative60(20.0)unknown7(2.3)Late recur Yes13(4.3)No288(95.7)*mean±SD
Overall average of NLR value was 2.16, median value was 1.83. The average NLR were 2.80±1.68 in patients with recurrences occurred after 5 years and 2.13±1.15 in patients without recurrence. The NLR cutoff value of 1.83 was determined by median value.
In 1.83≤NLR group has a higher incidence of recurrence after 5 years compared with NLR&lt;1.83 group (8yr DFS 99.2% vs. 93.3%, p = 0.021). Especially in luminal A(ER (+) or PR (+), HER-2(-)), 1.83≤NLR group has a higher incidence of recurrence after 5 years compared with NLR&lt;1.83 group (8yr DFS 100% vs. 87.0%, p = 0.015).
Conclusion
We found that pretreatment NLR is associated with late recurrence that occurs after five years. And we suggest that NLR could be used as one of the prognostic factor that can tell about late recurrence, 5-year after primary treatment.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-25.
Abstract P6-06-30: Are synchronous and metachronous bilateral breast cancers different? An immunohistochemical analysis aimed at intrinsic tumor phenotype
Authors: Senkus E , Szade J , Pieczynska B , Zaczek A , Pikiel J , Sosinska-Mielcarek K , Karpinska A , Jassem J 
Published: August 2014

Abstract
Background: The biology and pathomechanism of bilateral breast cancers is not fully understood: the risk of developing second (metachronous) breast cancer is 4-6 times higher than that of first primary in general population, whereas for synchronous breast cancers the number of cases is about 100 times higher than could be expected by chance alone. We compared the morphological and immunohistochemical characteristics of primary synchronous (sBBC) vs. metachronous (mBBC) bilateral breast cancers), with special focus on intrinsic tumor phenotype.
Methods: Tumor morphology and expression of 8 immunohistochemical markers were assessed in tissue microarrays containing primary breast tumor cores from 113 mBBC and 61 sBBC. Analyzed markers included hormone receptors (estrogen receptor, progesterone receptor), HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor. Surrogate intrinsic phenotypes were determined according to St Gallen 2011 criteria.
Results: mBBChad higher incidence of ductal histology (p = 0.037), lower estrogen receptor expression (p = 0.047), and higher expression of cytokeratin 5/6 (p = 0.017) and of vimentin (p = 0.008); in multivariate analysis only vimentin retained the significance (p = 0.01). Ten (13%) and 11 (26%) of mBBCand sBBC, respectively, had luminal A phenotype, 39 (50%) and 15 (36%) were luminal B HER2-negative, 13 (17%) and 12 (28%) - luminal B HER2-positive, 3 (4%) and 2 (5%) - HER2-positive (not luminal), and 12 (16%) and 2 (5%) had triple negative phenotype (p = 0.07).
Characteristics of mBBC and sBBCFeaturemBBC (%)sBBC (%)p valueDuctal histology98 (87)47 (77)0.037Grade 346 (41)17 (28)0.09Extensive intraductal component26 (23)18 (29)0.42Strong ER expression73 (67)48 (81)0.047Strong PR expression55 (49)38 (63)0.07HER2 positivity (2+, 3+)51 (46)29 (50)0.6Ki76 ≤14%24 (22)21 (35)0.06Surrogate intrinsic phenotype luminal A10 (13)11 (26) luminal B HER2-39 (50)15 (36) luminal B HER2+13 (17)12 (28)0.07triple negative12 (16)2 (5) HER2+ (non luminal)3 (4)2 (5) CK5/6 &gt;10%28 (26)6 (11)0.017Vimentin &gt;10%25 (23)4 (7)0.008E-cadherin (+)88 (83)49 (83)0.99EGFR (+)35 (32)11 (19)0.07
Conclusion: mBBC, compared to sBBC, are characterized by more aggressive phenotype, expressed by lower expression of estrogen receptor and stronger expression of cytokeratin /6 and vimentin; this does not, however, translate into substantial differences in the proportion of intrinsic tumor phenotypes.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-30.
Abstract P6-06-32: 4EVER: Does mTOR inhibition have a major clinical impact on bone health in postmenopausal women with hormone receptor positive (HR+) locally advanced breast cancer treated with everolimus (EVE) in combination with exemestane (EXE)?
Authors: Hadji P , Tesch H , Fasching PA , Lueftner DI , Janni W , Lux MP , Schneeweiss A , Decker T , Belleville E , Kreuzder J , Muth M , Wallwiener D 
Published: August 2014

Abstract
Introduction:
BOLERO-2, a multi-national, double-blind, placebo-controlled, phase 3 study in postmenopausal women with HR+, HER2- advanced breast cancer (BC) progressing after non-steroidal aromatase inhibitors (NSAI), showed significant benefit in PFS with the addition of the mTOR inhibitor EVE to EXE compared to EXE alone (Baselga J 2012). The BOLERO-2 bone sub study indicated an influence of EVE on bone health after 6 and 12 weeks of treatment (Gnant M 2012). To further investigate the long term influence of mTOR inhibition on bone health, we initiated the phase IIIb, multi-center, open label study 4EVER for postmenopausal women with HR+ locally advanced or metastatic breast cancer treated with EVE +EXE. The primary endpoint is the overall response rate (ORR) after 6 months. Secondary endpoints include progression free survival after 6 and 12 months, ORR after 12 months, overall survival, quality of life, health utilities and health care resources. The exploratory objectives focus amongst others on the assessment of biomarkers of bone turnover.
Methods:
Main inclusion criteria were postmenopausal women with metastatic or locally advanced, ER+, HER2- breast cancer refractory to NSAI. Markers of bone turnover (P-I-NP, CTX, OPG, RANKL, vitamin D, FSH and estradiol) are being assessed at baseline and after 4, 12 and 24 weeks on treatment.
Results:
Baseline characteristics: 334 postmenopausal patients were screened and 297 were enrolled in 5 months. The hormone receptor assessment was performed in 71.0% from primary tumor and in 29% from the metastases (ER+/PgR+ 77.5%, ER+/PgR- 21.5%). The mean time since initial diagnosis was 9.2 years. Mean time since first recurrence/ metastasis was 48.1 months and mean time since most recent recurrence / metastasis 2.4 months. The stage at primary diagnosis was M0 74.2% and M1 22.0%. 68.7% of the patients had bone lesions. Most recent antineoplastic medications were in the adjuvant (24.8%), neoadjuvant (1.1%) and palliative setting (71.0%). 25.6% of the patients had one, 16.4% two and 57.9% three and more prior therapies in metastatic setting.
The results of the baseline bone and hormone maker analysis for baseline and after 4, 12 and 24 weeks on treatment will be presented.
Conclusion:
This exploratory bone study will provide further insights into the influence of mTOR inhibition on bone turnover and overall bone health in women with advanced breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-32.
Abstract P6-06-34: Comparing recurrence risk scores derived from 4 immunohistochemistry stains (IHC4) versus oncoType DX
Authors: Miller DV , Jensen TA , Covington AD , Rosenthal R , Avent JM , Hansen J , Peck L , Wise PD , Leavitt MO , Wallentine JC , Rowley B 
Published: August 2014

Abstract
Background: Prognostically relevant biomarkers in breast cancers can be assayed using nucleic acid (e.g. OncoType DX) or protein based (e.g. immunohistochemistry (IHC)) detection stratagies. Nucleic acid tests measure many more markers compared to immunohistochemistry, but are weighted heavily for ER, PR, and HER2 in their prognostic scoring algorithms. Recent data suggest that a panel of 4 IHC stains (IHC4) may have equivalent prognostic ability to multigene assays. The aim of this study was to retrospectively compare IHC4 scores to OncoType DX recurrence scores in a large cohort of patients in our statewide health system.
Methods: Formalin-fixed paraffin-embedded breast cancer samples previously submitted for OncoType DX testing between 2008 and 2011 were obtained and sections stained for ER, PR, HER2, and Ki67 (the IHC4 staining panel). Stained slides were scanned digitally and scored using customized pathologist assisted image analysis algorithms (Leica Biosystems Aperio, Vista CA). The resulting data were used in the modified “Magee Equation 3” (Klein et al. Mod Pathol. 2013. PMID: 23503643) to calculate an IHC4 recurrence score on a numerically comparable scale to that used in the OncoType score. The IHC4 and Oncotype DX scores were directly compared for concordance and correlation.
Results: 280 breast cancer samples comprised the study cohort. The mean (median) IHC4 score was 20.13 (19), range: 11-42. The mean (median) OncoType score was 18.48 (16), range: 0-75. Using cut-offs of 0-17 for low risk, 18-30 for intermediate risk, and &gt;30 for high risk, the concordance data is shown in Table 1.
Comparison of scores from IHC4 and OncoType by Risk Category OncoType RS LowIntermedHigh Low80201IHC4 RSIntermed816819 High029RS = Recurrence Score
Pearson's correlation coefficient for the entire set was 0.6669. The overall concordance was 56.1%; one-step discordance 43.6%; and two-step discordance: 0.3%. Eliminating the intermediate scores, the concordance was 98.8%.
Conclusions: Reasonable agreement was seen between risk scores derived by IHC4 and OncoType DX. Only one discrepancy among 280 scores would have resulted in a different treatment recommendation (low risk by IHC4 and high risk by OncoType). If the IHC4 score is clearly high or low, one would not expect a dramatically different result from Oncotype DX, and the Oncotype DX test may not be needed.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-34.
Abstract P6-06-39: Chest wall invasion is a more significant prognostic factor than nodal spread, triple-negative or Her2 receptor status in stage III breast cancer: A large, single institution retrospective analysis
Authors: Ansley KC , Batten KG , Singel SM 
Published: August 2014

Abstract
Background
There is a significant variation in response to systemic treatment in stage III breast cancer that is not explained by hormone/Her2 receptor status alone. Identification of additional prognostic factors is needed to further stratify patients for additional treatment. According to the National Cancer Data Base, patients with stage IIIB breast cancer, characterized by having direct chest wall involvement regardless of lymph node spread, have a worse prognosis than patients with stage IIIC breast cancer, generally with significant lymph node involvement (41% vs. 49% 5-year overall survival). We hypothesized that chest wall invasion is an independent prognostic factor and may be more significant than regional nodal spread, triple-negative or Her2 -receptor status, or ethnicity.
Methods
Our retrospective study included 135 patients with stage IIIB or IIIC breast cancer seen at a large county hospital in Dallas, TX between 2008 and 2013. Patients were stratified into two groups based on whether they had chest wall invasion (T4) or not. Cases of inflammatory breast cancer (T4d) were excluded. Kaplan-Meier survival curves, the Log-Rank test, univariate and multivariate methods were used for statistical analysis. We evaluated the effects of chest wall involvement, ethnicity, and hormone receptor/Her2 status on overall survival.
Results
In patients with stage III breast cancer, those with chest wall invasion (T4) have a significantly decreased 5-year overall survival (OS) compared to patients with significant regional nodal spread (N3) (62% vs. 81%, p = 0.022, HR 2.3, 95% CI: 1.1-4.9). Univariate analysis of hormone receptor, Her2 status, African-American or Hispanic ethnicity, the presence of chest wall involvement, and significant regional lymph node involvement (N3 disease or not) showed that ER receptor status and the presence of chest wall involvement were the only significant prognostic factors (p = 0.006 and p = 0.022, respectively). Notably, the combination of ER-negativity and the presence of chest wall invasion predicts for worse prognosis than either alone (p = 0.0011, HR 1.6, 95% CI: 1.2-2.2).
Conclusion and Discussion
Chest wall invasion was an independent predictor for decreased overall survival in stage III breast cancer. This could explain in part why patients with stage IIIB breast cancer have worse overall survival than patients with stage IIIC. There may be an intrinsic biological difference between breast cancer cells that directly invade surrounding chest wall and those that have nodal spread as the main route of metastasis. An inflammatory component in those with chest wall invasion may allow these tumors to be more aggressive and additional research is needed to target potential genes for therapy.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-39.
Abstract P6-06-40: Analysis of outcome according to risk factors in the randomized phase III TURANDOT trial evaluating first-line bevacizumab-containing therapy for HER2-negative locally recurrent/metastatic breast cancer (LR/mBC)
Authors: Brodowicz T , Pienkowski T , Beslija S , Melichar B , Lang I , Inbar MJ , Anghel R , Spanik S , Ahlers S , Zielinski C 
Published: August 2014

Abstract
Background: The randomized phase III TURANDOT trial compared first-line bevacizumab (BEV) + paclitaxel (PAC) vs BEV + capecitabine (CAP) in HER2-negative LR/mBC [Lang, Lancet Oncol 2013]. At the prespecified interim analysis there was no detectable difference in overall survival (OS; primary endpoint) between treatment groups, but the secondary endpoints of progression-free survival (PFS) and objective response rate (ORR) favored BEV-PAC. We sought to identify patient populations defined by risk factors that may be most appropriately treated with one or other of the regimens.
Methods: Patients with HER2-negative LR/mBC who had received no prior chemotherapy for LR/mBC were randomized to either BEV-PAC (BEV 10 mg/kg d1 & 15 + PAC 90 mg/m2 d1, 8, & 15 q4w) or BEV-CAP (BEV 15 mg/kg d1 + CAP 1000 mg/m2 bid d1-14 q3w). The study population was categorized into three cohorts: triple-negative (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High-risk and low-risk HR+ were defined, respectively, as having ≥2 vs ≤1 of the following four risk factors: disease-free interval ≤24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; ≥3 metastatic sites.
Results: Baseline characteristics, efficacy, and safety by treatment arm are summarized below for the three cohorts. Although PFS results in all cohorts favored BEV-PAC, interim OS results showed a trend in favor of BEV-PAC in TNBC patients and in favor of BEV-CAP in low-risk HR+ patients. Grade ≥3 adverse events were less common with BEV-CAP than BEV-PAC in all three cohorts.
TNBCHigh-risk HR+Low-risk HR+ BEV-PAC (n = 63)BEV-CAP (n = 67)BEV-PAC (n = 146)BEV-CAP (n = 162)BEV-PAC (n = 75)BEV-CAP (n = 50)Median age, years545658576161ECOG PS 0,%756068666366PFS Events, n (%)50 (79)54 (81)93 (64)125 (77)33 (44)35 (70)Median, months (95% CI)9.0 (7.8-10.7)5.6 (4.9-8.0)11.1 (10.4-13.4)8.3 (7.1-10.7)14.4 (10.4-20.5)11.5 (8.1-16.3)HR (95% CI)a1.37 (0.93-2.02)1.29 (0.98-1.69)1.39 (0.86-2.25)OS Events, n (%)28 (44)34 (51)50 (34)52 (32)18 (24)11 (22)1-year OS rate,%786380828590HR (95% CI)a1.33 (0.80-2.19)0.97 (0.66-1.43)0.80 (0.38-1.69)Grade ≥3 AEs,%634261516148aBEV-CAP vs BEV-PAC
Conclusion: The simple risk factor index is prognostic for both PFS and OS and may be used to guide treatment choice when selecting BEV-containing therapy, balancing outcome with safety profile and patient preference. Final analysis of OS is expected in 2014.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-40.
Abstract P6-06-44: Role of uPA and PAI-1 mRNA expression as prognostic factors in molecular subtypes of breast cancer
Authors: Witzel I , Milde-Langosch K , Schmidt M , Karn T , Rody A , Wirtz R , Jänicke F , Müller V 
Published: August 2014

Abstract
Background: Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) determined by ELISA from fresh-frozen tumor tissue have been evaluated as prognostic factors in prospectively randomized trials in node-negative breast cancer. However, uPA and PAI-1 mRNA expression might reveal new clinically relevant information using paraffin-embedded tumor tissue.
Methods: We evaluated uPA and PAI-1 mRNA expression with the Affymetrix HG-U 133A array also within molecular subgroups of breast cancer in a finding cohort of breast cancer patients (cohort A; n = 548). We validated mRNA expression in a cohort of HER2 positive breast cancer patients (cohort B, n = 347). For uPA and PAI-1, mRNA values below and above the median were compared in two different probesets. “Luminal”, “triple-negative” and “HER2 positive” subcohorts were defined by ESR1 and ERBB2 mRNA expression using pre-defined cut-offs.
Results: In cohort A, elevated PAI-1 mRNA expression was associated with shorter disease-free survival (DFS) and overall survival (OS), elevated uPA mRNA expression was associated with shorter OS. Regarding different molecular subgroups, 71% (n = 388) of tumors had a luminal, 13% (n = 69) a HER2 positive and 17% (n = 91) a triple-negative subtype. Only in the HER2 positive subgroup, elevated PAI-1 mRNA expression was associated with shorter disease-free survival and overall survival (p = 0.003 for DFS and p = 0.012 for OS). Same results were found for uPA in HER2 positive patients (DFS, p = 0.027 and OS, p = 0.011). In contrast, no association between both markers and DFS and OS could be seen in the luminal or triple-negative subgroups. In the HER2 positive validation cohort B elevated uPA and PAI-1 mRNA expression showed a strong association with shorter DFS (p = 0.013 for PAI-1, p = 0.001 for uPA).
Conclusion: Results of this study demonstrate that the prognostic impact of uPA and PAI-1 mRNA expression was observed mainly in patients with HER2 positive tumors.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-44.