bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-07-21: A Comparison of Two Methods for the Detection of Circulating Tumor Cells (CTCs) in Patients (pts) with Early and Metastatic Breast Cancer (BC): RT-PCR for Cytokeratin (CK) −19 mRNA Versus the CellSearch System.
Authors: Politaki E , Agelaki S , Apostolaki S , Perraki M , Hatzidaki D , Lianidou ES , Mavroudis D , Georgoulias V 
Published: June 2012

Abstract
Background: Different methods are available for the detection of CTCs in pts with BC, however, the variable performance of these assays, the heterogeneity of CTCs, and the possible treatment-induced alteration of the markers evaluated, imply that no ideal method currently exists. We compared the efficiency of two methods to detect CTCs in pts with BC.
Patients and Methods: Blood was obtained from 200 pts with early and 164 with metastatic BC before the start of adjuvant or first-line chemotherapy, respectively. Different aliquots of the same sample were evaluated by RT-PCR for CK-19 mRNA and by the CellSearch System. Blood samples were available after the end of adjuvant or first-line therapy in 99 and 93 pts, respectively. CTCs in 23 and 7.5 ml of blood were enumerated by CellSearch, in adjuvant and metastatic pts, respectively. Cut-off values of ≥1 and ≥2 CTCs/23 ml and ≥2 and ≥5 CTCs/7.5 ml were used. Twenty ml of blood were obtained for mRNA extraction in all RT-PCR experiments.
Results: In early BC, 18.0% of samples were positive prior to therapy by RT-PCR and 37.0% (CTC≥1) and 16.5% (CTC≥2) by CellSearch. No significant correlation was shown for the detection of CTCs between methods. Overall (positive and negative) concordance was 62% for CTC≥1 and 73.5% for CTC≥2 (Chi-Square, p=0.161 and p=0.307). Post-chemotherapy, the positivity rate was 33.6% (CTC≥1) and 18.8% (CTC≥2) by CellSearch and 11.6% by RT-PCR (Spearman, R=-0.031, p=0.761). Overall agreement was 60.6% (CTC≥1) and 71.4% (CTC≥2) (Chi-Square, p=0.771 and p=0.708). In the metastatic setting, 37.8% of the samples were positive by RT-PCR, and 50% (CTC≥2) or 32.3% (CTC≥5), by CellSearch (Spearman, R=0.373, p=0.0001). Overall agreement was 70.0% for CTC≥5 (Chi-Square, p=0.0001). Post-chemotherapy, 21% were positive by RT-PCR and 13.7% and 8.4% by CellSearch for CTC≥2 and ≥5, respectively (Spearman, R=0.194, p=0.063). Overall concordance for CTC≥5 was 79.6% (Chi-Square, p=0.017). Agreement was also observed for CTC≥2, pre-and post-chemotherapy (Chi-Square, p=0.0001 and p=0.010). The concordance rates in the adjuvant and metastatic settings are shown in Table 1.

Conclusions: A high concordance between the two methods was detected in metastatic but not in early disease. Patient follow-up will determine the clinical relevance of each individual assay or their combination in the assessment of patient prognosis.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-21.
P4-09-14: Differential Expression of the Akt1 Isoform in Mammary Ductal Carcinoma.
Authors: Sanders AJ , Mansel RE , Jiang WG 
Published: June 2012

Abstract
Introduction:
AKT1 is an oncogenic protein and controls numerous cellular processes in both normal and cancerous cells. There are three isoforms, Akt1 (PKBα), Akt2 (PKBβ) and Akt3 (PKBγ). Frequently, regulation of the Akt pathway is disrupted in cancerous cells and interest within the scientific community has focused on the use of this pathway in treating cancer. However, recent studies have also implicated that Akt1 may act to limit invasive migration of breast cancer cells suggesting the potential of this isoform to have both pro- and anti- tumorigenic roles. In the current study we examined the expression profile of Akt1 in a cohort of ducal carcinoma of the breast. Methods:
Quantitative transcript analysis was used to assess the expression levels of Akt1 in a range of ductal carcinoma of the breast (n=85) and normal samples. Expression levels were used in conjunction with clinical and pathological data, as well as the clinical outcomes of the patients (median follow-up 120 months).
Results:
Expression of Akt1 levels in the mammary ductal carcinoma cohort demonstrated a lower level of transcript expression in the lower grade and stage cancers. Levels of Akt1 were found to be significantly lower in grade 1 ductal breast carcinomas compared to the combined higher grade 1 and 2 carcinomas (ductal carcinoma grade 1 median = 3.7 vs ductal carcinoma grade 2,3 median = 33.6, p = 0.01). In addition to this, median transcript levels of Akt1 were found to increase with increasing TNM stage of the ductal carcinoma (Median values of Akt1 in ductal carcinoma TNM 1 = 5.9, TNM 2 = 63.6, TNM 3 = 533 and TNM 4 = 13680). This enhanced expression of Akt1 in higher TNM stages, compared to TNM stage 1, was found to be significant in most cases (TNM1 vs TNM2, p = 0.03; TNM1 vs TNM3, p = 0.15; TNM1 vs TNM4, p = 0.03).
Conclusion:
Variable expression of Akt1 was seen throughout the mammary ductal carcinoma cohort and correlated with a number of prognostic factors. Akt1 transcript levels were found to be significantly reduced in the low grade 1 and TNM1 stages when compared to the higher grades and TNM stages. Our current data suggests that low levels of Akt1 may be associated with better clinical patient prognosis in mammary ductal carcinoma.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-14.
P4-09-18: Australian Decision Impact Study: The Impact of Oncotype DX Recurrence Score (RS) on Adjuvant Treatment Decisions in Hormone Receptor Positive (HR+), Node Negative (N0) and Node Positive (N+) Early Stage Breast Cancer (ESBC) in the Multidisciplinary Clinic (MDC).
Authors: de Boer RH , Baker C , Speakman D , Mann B 
Published: June 2012

Abstract
Introduction: There has been increasing interest in more accurately defining the need for chemotherapy in patients with HR+ ESBC. Oncotype DX® has been shown to provide prognostic and predictive information beyond traditional histopathological factors. Prior clinical impact studies have focused on decisions made by individual practitioners. In Australia, the MDC has become the standard forum for determining treatment decisions. In this study, we have assessed how the RS influences adjuvant systemic treatment decisions in the MDC at 4 separate hospitals. Methods: Patients with unifocal HR+, HER2−ve ESBC, N0 and N+ (1-3 positive nodes, including micrometastases and isolated tumour cells) and no contraindication to adjuvant chemotherapy (CTx) or endocrine therapy (H) were eligible. A total of 150 patients will be entered. Systemic adjuvant treatment recommendations were made and recorded in the MDC, both before and after testing with Oncotype DX. The primary endpoint was the overall change in the treatment recommendation. Other endpoints included confidence in recommendations, assessment of impact of the RS, and treatment the patient actually received. Results: Currently, RS results on 84 patients are available. Patient age range is 33–82 years. There are 56 (67%) N0 pts and 28 (33%) N+. Overall, 37 (44%) women had low, 36 (43%) intermediate and 11 (13%) high RS. The RS changed the initial treatment recommendations in 20 (24%) patients. Of the 34 patients initially recommended CTx+H, there was a shift to H alone for 12 (35%), whilst of the 50 patients initially recommended H alone, 8 (16%) shifted to CTx+H. A shift in treatment recommendations was reported for 8/37 (22%) pts with low, 8/36 (22%) with intermediate and 4/11 (36%) with high RS. 13/56 (23%) of N0 pts had a change in recommendation, whilst 7/28 (25%) N+ pts changed (table 1). 5 patients have decided against the final MDC recommendations: 3 chose CTx+H after recommendation of H (RS of 13,19 and 21 respectively), and 2 declined a CTx+H recommendation (RS of 19 and 25). Conclusion: Early results of our Australian study suggest an impact of Oncotype DX RS on adjuvant treatment decision making in the MDC setting. Updated results on the full 150 patients will be presented at the meeting.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-18.
P4-09-19: PCNA+ Tumor Associated Macrophages Are Associated with M1 and M2 Gene Expression, and Confer Poor Prognosis in the Absence of Anti-Tumor Immune Environment.
Authors: Mukhtar R , Wolf D , Tandon V , Zhu J , Lenburg M , van't Veer L , Campbell MJ 
Published: June 2012

Abstract
Background
Tumor associated macrophages (TAMs) promote breast tumor progression through the production of angiogenic factors, stromal breakdown factors, and the suppression of adaptive immunity. TAMs are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 anti-tumoral and M2 pro-tumoral phenotypes. We previously identified a population of PCNA+ TAMs associated with high grade, hormone receptor (HR) negative tumors with poor outcomes. We hypothesized that high PCNA+ TAMs would be associated with expression of M2 related genes.
Methods
We used immunohistochemistry to measure PCNA+ TAM levels (double positive for PCNA and CD68) in 135 invasive breast cancer cases from the I-SPY 1 Trial, a prospective neoadjuvant trial with serial core biopsies and gene array data. We developed gene-sets representing M1 related, M2 related, and anti-tumoral immune response (represented by cytotoxic T cells and MHC Class II) genes based on literature review. We compared PCNA+ TAM levels, expression of these gene-sets, and outcomes.
Results
Higher than mean PCNA+ TAM counts were associated with increasing grade (p &lt; 0.001), HR negativity (p &lt; 0.001), and decreased recurrence free survival (RFS, p = 0.05). Among subjects who had a pathologic complete response (pCR), there was no difference in RFS between those with high versus low PCNA+ TAMs. Among subjects without pCR, those with high PCNA+ TAMs had significantly worse RFS than those with low PCNA+ TAMs (p = 0.0028). In the 95 subjects with both PCNA+ TAM results and gene expression arrays available, high PCNA+ TAM levels were associated with more M1 than M2 related genes. The gene-set representing anti-tumoral immune environment was not by itself associated with RFS. However, those subjects with both high PCNA+ TAMs and the absence of anti-tumoral immune response gene expression had significantly worse RFS than those with high PCNA+ TAMs but the presence of anti-tumoral immune related genes (p = 0.01).

Conclusions
High PCNA+ TAMs had different effects on outcomes depending on tumoral immune environment. Instead of being purely M2 macrophages, PCNA+ TAMs likely represent a heterogeneous mixture of TAMs with different polarization states. Additional markers are needed to distinguish anti-tumoral from pro-tumoral PCNA+ TAMs.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-19.
P4-09-24: Correlation of Aurora Family Member Expression with Clinical Breast Cancer Prognosis.
Authors: Annakesavan A , Sanders AJ , Harding KG , Jiang WG 
Published: June 2012

Abstract
Introduction:
Aurora-A, Aurora-B and Aurora-C are a family of protein kinases which have been identified as key regulators of the mitotic cell division process. Members of this group have been linked with pro-tumorigenic effects and have been reported as being up-regulated in certain cancers. Our current study examines the expression profile of the Aurora-A, Aurora-B and Aurora-C members in a breast cancer cohort in relation to a number of predictive factors.
Materials and Methods:
The expression of Aurora-A, Aurora-B and Aurora-C was examined in a breast cancer cohort using quantitative real time PCR (normal samples n = 34, tumour samples n = 109) and immunhistochemistry (IHC). Expression of the aurora members was related to clinical parameters such as staging and Nottingham prognostic index (NPI).
Results:
Examination of Aurora-A levels in the breast cancer cohort revealed an association of Aurora-A expression with NPI grouping. High levels of Aurora-A levels were seen in NPI-1 and NPI-2 stages (NPI-1 median = 66.0, NPI-2 median = 64.3), with expression reducing significantly at the higher NPI-3 group (NPI-3 median = 20.3; p = 0.029 vs NPI-2 and p = 0.009 vs NPI-1 respectively). Additionally, Aurora-A levels were found to be significantly lower in grade 3 cancers compared to grade 1 (median grade 1 = 86.5 vs median grade 3 levels = 52.6, p = 0.04). In contrast to this, examination of Aurora-C levels in the cohort identified a relatively low level of Aurora-C in NPI-1 and NPI-2 group (median values NPI-1 = 88, NPI-2 = 34.4) compared to a substantial increase in Aurora-C expression in NPI-3 (median value = 1602, p = 0.05 vs NPI-1 and p = 0.06 vs NPI-2). Aurora-B expression levels did not exhibit any significant differences within the breast cancer cohort.
Conclusions:
Differential expression of Aurora-A, Aurora-B and Aurora-C were observed within the breast cancer cohort. Higher Aurora-A expression was associated with low NPI groups and grades and potentially with better patient prognosis whereas lower levels were seen in the poorer prognostic NPI-3 group and higher grades. An opposite trend was seen in Aurora-C where lower levels were associated with the NPI-1 and NPI-2 groups and significantly higher levels were seen in the NPI-3 group. Aurora-B levels appeared to have no predictive function. This data suggests that together Aurora-A and Aurora-C levels, within a patient may be useful for predicting patient outcome.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-24.
P4-09-29: A Nomogram To Predict Prognosis in Node-Negative Breast Carcinoma.
Authors: Mazouni C , Spyratos F , Romain S , Fina F , Bonnier P , Ouafik L , Martin P-M 
Published: June 2012

Abstract
Background: Currently, the usefulness of conventional markers for breast carcinoma is limited to assess individual outcome. A statistical model was developed to improve the prognostic accuracy using multiple conventional and emerging prognostic biomarkers.
Methods: A total of 305 node-negative breast carcinomas who underwent surgery (+/− radiotherapy) but no adjuvant treatment was selected. Putative prognosis factors including age, tumor size, ER, PR, SBR grading, urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and thymidine kinase (TK) were evaluated. The developed model was internally validated using Harrell's concordance index and calibrated. An external validation of the new model is warranted.
Results: Age (p&lt;0.001), PR (p= 0.02), and PAI-1(p=&lt;0.001) were included in the Cox regression model predicting overall survival at 5-years. Internal validation revealed a concordance index of 0.711 to 0.694 before and after calibration.
Conclusion: A nomogram can be used to predict probability survival curves for individual breast cancer patients and the effect of treatment options can be evaluated using these models.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-29.
P4-09-33: The Prognostic Significance of Metaplastic Carcinoma of the Breast – A Comprehensive Comparison Study with Common Breast Cancers.
Authors: Lai H-W , Kuo S-J , Chen D-R , Chen S-T 
Published: June 2012

Abstract
Purpose : Metaplastic carcinoma of the breast (MCB) is a rare histological subtype of breast cancer with incidence less than 1%. Due to its rarity, the clinical characteristics and prognostic significance of MCB compared with other common breast cancer, such as infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) are not clear and controversial between different reports. We performed a multi-institutional cases collective comparison study to evaluate the clinical characteristics and prognostic status with IDC and ILC.
Materials and methods : Cases of MCB were enrolled from 4 medical centers in Taiwan. Forty-five MCB patients combined with 1777 IDC and 53 ILC patients from cancer registry database of Changhua Christian Hospital (CCH) comprised the current study. The patients’ demographic data, tumor characteristics and prognosis of MCB were analyzed and compared with IDC, and ILC. To further clarify the prognostic difference between MCB and IDC, a case control analysis was performed to minimize the effect of tumor size, lymph node status and other clinicopathologic factors. The disease free survival (DFS) and overall survival (OS) between groups were compared.
Results : Compared with IDC, MCB was associated with older age, larger tumor size, lesser lymph node positive rate, higher distant metastasis, higher tumor grade, lower ER positive tumor, and higher triple negative breast cancer subtype (TNBC). Compared with IDC, MCB was associated with worse OS (p=0.031), but no difference in DFS (p=0.071). While MCB was not statistically different from ILC in both DFS and OS (p=0.132 and 0.289, respectively). To eliminate the influence of other prognostic factors, 135 cases controlled IDC with comparable clinicopathologic parameters were enrolled to compare with those 45 MCB patients.

Compared with cases controlled IDC group, the MCB patients remained showed poorer OS (p=0.040), but not different in DFS (p=0.439).
Conclusion : MCB was associated with poorer OS compared with IDC, and this poorer prognosis was related to tumor behavior rather than clinicopathologic factors.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-33.
P4-09-34: Luminal Infiltrating Lobular Carcinoma of the Breast: Clinical and Prognostic Features.
Authors: Valdiviezo NI , Vega E , Castañeda C , Flores C , Mendiola CD , Manso LM , Dorta M , De Velasco GA , Cortés-Funés H , Ghanem I , Ciruelos EM 
Published: June 2012

Abstract
Background
Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are the two most common histologic types of invasive breast cancer. Previous studies have demonstrated distinctive clinical and biologic characteristics, however some features of ILC are yet uncertain like the relationship with the particular subtypes according to the gene expression profile.
The purpose of our study is to analyze how the patients with ILC differ from IDC regarding of percentage of luminal subtype, the tumor factors, treatment and patterns of recurrence.
Patients and Methods
We assessed 1190 breast cancer patients treated at the Hospital Universitario 12 de Octubre between 1995 and 2006 categorized as having ILC or IDC pure types.
Results: One thousand one hundred ninety tumors were included, being ILC 223 patients (18, 7%), IDC 967 patients (81, 3%) and 200 patients (10%) were luminal HER2+. The current analysis is limited to the 990 patients classified as luminal HER2−.
Median age was 59, 2 years for ILC and 58, 8 for IDC, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T3: 15, 2% vs. 4, 8%, ***p&lt;0.01), lesser nodal involvement (35% vs 42, 7% p 0.048) and lower Ki67 expression (62, 6% vs. 52, 2% p=0.01). The proportion of luminal A subtype was greater in ILC (56, 3% vs. 46, 7% p=0.01). Mastectomy was more frequently performed for ILC (61, 2 % vs. 47, 7%, p=0.01). Regarding systemic therapy, 127(62,4%) ILC patients and 450 (57, 2%) IDC patients received adjuvant chemotherapy (QT). That was anthracycline-based in most cases (47, 2% for ILC and 46,4% for IDC). Adjuvant hormonal treatment was prescribed equally among both groups (196, 96% ILC and 739, 94% IDC), being the most commonly used drug ***tamoxifen.
With a median follow-up of 94 months, 45 ILC patients (22%) and 159(20, 2%) IDC relapsed. No differences were observed in DFS (p=0, 81) or OS (p=0, 47).
The most frequent metastatic site was bone (33% for ILC and 40, 8% for IDC), followed by local relapses (17, 7% for ILC vs. 17% for IDC) and liver (15, 5% for ILC vs. 15, 7% for IDC). ILC was associated with an increased incidence of peritoneal/mesenteric metastases (8 pts 17, 7% vs. 1pts 0,6% ***p&lt;0.01) and a lower incidence of lung relapses (8, 8% vs. 19, 4 % pts p&lt;0.05).
Conclusion: Luminal HER2− Infiltrating lobular carcinoma carries distinct clinicopathological features. In our study, ILC had similar prognosis as IDC.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-34.
P4-10-06: Evaluation of BRCAPro Risk Assessment Model in Patients with Ductal Carcinoma In Situ.
Authors: Muse KI , Elsayegh N , Gutierrez-Barrera AM , Kuerer H , Valero V , Litton JK , Hortobagyi GN , Arun BK 
Published: June 2012

Abstract
Background: The BRCAPRo model is used to predict a patient's likelihood to possess a BRCA1 or BRCA2 gene mutation based upon personal and family history. Ductal carcinoma in situ (DCIS) is considered a non-invasive condition which can progress to an invasive breast cancer if left untreated. Currently, DCIS is not specifically accounted for in the BRCAPro model, thereby causing DCIS to be weighted in the same manner as an invasive breast cancer diagnosis. Historically, a diagnosis of DCIS has been entered as having developed into an invasive breast cancer ten years later. However, there are no standard guidelines of how DCIS should be entered. We sought to determine if there were any differences in how DCIS was treated in the BRCAPro model to predict the more effective method in calculating the BRCAPro. Methods: Women with pure DCIS, who were referred for genetic counseling and underwent genetic testing, were included in the study. The likelihood of carrying a BRCA mutation was calculated using the BRCAPRO model (Version 5.1). Patient characteristics which were entered into the BRCAPro model include: tumor markers (estrogen receptor-ER and progesterone receptor-PR), history of oophorectomy prior to diagnosis, family history of 1st and 2nd degree relatives with breast and ovarian cancer, race and Ashkenazi Jewish ancestry. Each patient's BRCAPro risk estimate was calculated and compared by entering DCIS at the presenting age of diagnosis and by adding 10 years to the age of diagnosis. Descriptive statistics and a student's t-test were used to compare BRCAPro estimates between the two groups. Results: Ninety-five patients with pure DCIS underwent genetic counseling and testing. The average age of DCIS diagnosis was 45 years (range 26–65). Of the 95 DCIS patients included in the study 21% (n=20) tested positive for a BRCA gene mutation (8 BRCA1 and 12 BRCA2), 77% (n=74) test negative and 0.01% (n=1) had a variant of uncertain significance. Overall, DCIS patients who tested positive for a BRCA mutation had a higher BRCAPro (40%) than patients who tested negative (12%) when presenting age of diagnosis was assessed. When 10 years was added, the BRCAPro estimate was still higher amongst BRCA positive patients (28%) than BRCA negative patients (8%). The mean BRCAPro probability when DCIS was entered at presenting age of diagnosis was 18% (0.1−95.4) versus 12% (0.1−89.9) when calculated 10 years later. Conclusion: In our cohort there was no significant difference in BRCAPro probability whether DCIS was entered at the presenting age of diagnosis or 10 years later (p=0.1). However, future studies are needed to determine the most effective method to incorporate DCIS into the BRCAPro model in order to determine those individuals who may or may not be at increase risk to possess a BRCA gene mutation.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-06.