bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract OT3-2-01: Influence of strength and endurance training on selected physical and psychological parameters and on immune system, metabolism and circulating tumor cells during adjuvant chemotherapy
Authors: Mundhenke C , Weisser B , Keller L , Sanders L , Summa B , Duerkop J , Schmidt T , Jonat W 
Published: August 2014

Abstract
Background: Reduced quality of life, limited performance and fatigue are commonly observed side effects of breast cancer systemic treatment. In previous studies sport therapy could improve these symptoms. Sport has also been reported to positively impact the clinical course of the disease. So far it has remained unclear if these influences on clinical outcome are caused by alterations in the immune system or in tumor biology or in glucose or fat metabolism.
The aim of this study is to analyse the implications of individual interventions in exercise therapy on endurance, muscle strength, fatigue and quality of life, alterations in the immune system or in tumor biology or in glucose or fat metabolism for breast cancer patients during chemo therapy.
Method: The trial is prospectively randomised and controlled and will involve 60 breast cancer patients receiving adjuvant chemotherapy. 20 patients each are randomized into a strength training group, an endurance training group or a control group (with standard care). At the beginning and after 12 weeks the following tests are undertaken: isometric maximum strength test, a PWC 150 test to determine the endurance of patients. The standardised questionnaire EORTC QLQ C30 including module BR23 to measure quality of life and the questionnaire MFI-20 to determine symptoms of fatigue are filled in. Questionnair D2 measures ability to concentrate. Immunologic parameters as CD4, CD8 and T-REG-cells (FACS-Analysis), the number of the circulating tumour cells (measured by density gradient centrifugation) and also the concentration of glucose, insulin, leptin and adiponectin are being measured at study entry and after 12 weeks.
Momentarily patients are being screened, recruited and randomised into the trial. The final evaluation of the results is planned II/ 2013.
Discussion: The purpose of this study is to show if additional value can be added by individualized strength- or endurance training. Stabilisation or improvement of maximum strength and endurance during chemotherapy, as well as increase of quality of life and reduction of symptoms of fatigue would be a major improvement. Knowledge about effects of physical activity on circulating tumour cells as well as on immunologic alterations and on glucose and fat metabolism under chemotherapy could lead to a more specific counseling of patients and an individualized training program during chemotherapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-2-01.
Abstract OT3-3-01: Eniluracil + 5-fluorouracil + leucovorin (EFL) vs. capecitabine phase 2 trial for metastatic breast cancer
Authors: Rivera E , Chang JC , Semiglazov V , Gorbunova V , Manikhas A , Krasnozhon D , Kirby G , Spector T 
Published: August 2014

Abstract
Based on a modified dosing protocol designed to optimize efficacy, an open-label EFL vs. capecitabine (4:3 randomization) Phase 2 trial for metastatic breast cancer is in progress. Eniluracil inactivates dihydropyrimidine dehydrogenase, thereby preventing the formation of α-fluoro-β-alanine, and conferring 100% oral bioavailability and a 5 hr half-life on 5-fluorouracil (5-FU). Study drugs are administered orally for 1st- or 2nd-line treatment for metastatic disease in patients previously treated with an anthracycline and a taxane. Arm 1: eniluracil (40 mg) taken 11–16 hr before 5-FU (30 mg/m2); leucovorin (30 mg) taken with 5-FU and the next day. The regimen is administered once/week for 3 weeks/4 weeks. Arm 2: capecitabine (1000 mg/m2) taken bid for 14 days/21days. Arm 2 patients with disease progression could crossover to take EFL in Arm X. Two sites in the USA and 19 in Russia are enrolling. Currently, 115 patients (21% are 1st-line, 70% had previous 5-FU treatment) are enrolled and 83 have had tumor assessments. EFL was well tolerated with no unexpected toxicities. As of May 2012, there were 11, 7, & 1 partial responses in Arms 1, 2, & X, respectively. The primary endpoint, progression-free survival, will be determined approximately 7.5 months after the trial is enrolled with 140 evaluable patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-01.
Abstract P1-01-19: Prediction of axillary lymph node status in male breast carcinoma
Authors: Vaysse C , Sroussi J , Mallon P , Feron J-G , Rivain A-L , Ngo C , Belichard C , Lasry S , Pierga J-Y , Couturaud B , Fitoussi A , Laki F , Fourchotte V , Alran S , Kirova YM , Vincent-Salomon A , Sastre-Garau X , Sigal-Zafrani B , Rouzier R , Reyal F 
Published: August 2014

Abstract
Background: To evaluate whether predictive factors of axillary lymph node metastasis in female breast cancer (BC) are similar in male BC.
Patients and methods: From January 1994 to May 2011, we recorded 80 non-metastatic male BC treated at Institut Curie. We analysed the calibration and discrimination performance of two nomograms (Institut Curie (IC), Memorian Sloan-Kettering Cancer Center (MSKCC)) originally designed to predict axillary lymph node metastases in female BC.
Results: 55% and 24% of the tumours were pT1 and pT4 respectively. 46% demonstrated axillary lymph node metastasis. 99% were estrogen receptor positive and 94% HER2 negative. Lymph node status was the only significant prognostic factor of overall survival (p = 0.012). The area under curve (AUC) of IC and MSKCC nomograms were 0.66 (95%CI, 0.54–0.79) and 0.64 (95% CI, 0.52–0.76) respectively. The calibration of these two models was inadequate (Table 1).

Conclusion: Multivariate models designed to predict axillary lymph node metastases for female BC weren't effective in our male BC series. Our results may be explained by a) small sample size b) different biological determinants influencing axillary metastasis in male BC compared to female BC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-19.
Abstract P1-01-20: Clinicopathlogic Analysis of Invasive Breast Carcinoma with Micropapillary Component
Authors: Yamanaka T , Suganuma N , Yamanaka A , Kojima I , Nishiyama S , Mukaibashi T , Nakayama H , Matsuura H , Matsuzu K , Chiba A , Inaba M , Rino Y , Yoshida A , Shimizu S , Masuda M 
Published: August 2014

Abstract
Background: Invasive micropapillary carcinoma(IMPC) is a rare variant of invasive breast cancer that is associated with a high incidence of lymph node(LN) metastasis. But, the meaning of focal micropapillary component has not been fully elucidated.
Methods: We retrospectively reviewed 88 invasive breast carcinoma cases with IMPC and focal micropapillary component.
Results: Sixty-four cases had micropapillary component only in operative specimens, 18 cases had only in core-needle specimens, and 6 cases had in both. Sixteen were diagnosed as IMPC, and 72 cases had focal micropapillary component with other histological type of invasive breast carcinoma; 65 cases with invasive ductal carcinoma, 6 cases with mucinous carcinoma and one with metaplastic carcinoma. There was one male patient. Mean age was 56.5 years old. Median tumor size was 2.5 cm. Forty two (47.7%) cases were nuclear grade(NG)1, 16 (18.2%) were NG2 and 30 (34.1%) were NG3. Seventy eight cases (90%) were ERand/orPgR positive and 18.5% were HER2 positive. Six cases had distant metastasis at initial diagnosis. LN metastases were observed in 63.6% of all cases, and this high rate of LN metastasis could be seen even in small tumor group; 45.5% in cases with tumor equal or less than 2 cm. In the group of IMPC, 40.0% had LN metastasis, and 56.9% in cases with focal micropapillary component. There was no significant difference between IMPC and focal micropapillary component by univariate analysis(p = 0.055). Multivariate analysis of all cases showed that tumor size(&gt;2cm)(p = 0.047), NG(1 vs 2&3, p = 0.017), and lymphatic invasion(p = 0.001) were significantly associated with LN metastasis. No significant difference between IMPC and focal micropapillary component was showed by multivariate analysis also (p = 0.60). Hormone receptor status or HER2 status were also not correlated(p = 0.92, p = 0.27 respectively). Among female patients without neoadjuvant chemotherapy, sentinel lymph node biopsy(SLNB) were underwent in 38 cases, and 16 cases (42.1%) had positive sentinel lymph node(SLN). Fourteen patients underwent additional axillary dissection and 7 cases (50%) had non-SLN metastases. Among patients with SLNB, 12 patients had micropapillary component in needle biopsy specimens, and 6 (50%) cases had positive SLN.
Conclusion: Our data showed very high rate of LN metastasis in patients with micropapillary component, and this tendency still exists in cases with only focal micropapillary pattern. High positivity of SLNB was observed in these groups, and our data suggests that the findings of micropapillary component in CNB specimen could be used as a predictor of SLN metastasis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-20.
Abstract P1-01-23: Increased Diagnostic Performance of Sentinel Lymph Node Biopsy Combined with Radiologic-pathologic Factors After Neoadjuvant Chemotherapy in Breast Cancer Patients with Cytologically Proven Node Metastasis at Diagnosis
Authors: Park S , Koo JS , Kim MJ , Park JM , Cho JH , Hwang H , Park HS , Kim E-K , Kim SI , Park B-W 
Published: August 2014

Abstract
Background: It is undetermined whether sentinel lymph node biopsy (SLNB) is feasible and accurate for predicting final nodal status after neoadjuvant chemotherapy (NCT) in breast cancer patients with cytologically proven node metastasis at the time of diagnosis, although currently completion node dissection is a standard surgical procedure for the management of axilla. The aim of this study was to investigate diagnostic performance of SLNB after NCT in this subgroup.
Methods: Of 374 patients with T1-T3 breast cancer who received NCT, 178 had initially biopsy proven axillary/supraclavicular metastasis and subsequently underwent SLNB using radioisotope alone followed by completion node dissection between 2008 and 2011. Detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV), and accuracy of SLNB were retrospectively analyzed and it was explored using regression analysis whether combination with clinicopathologic factors improved performance.
Results: At initial presentation, 60.7% of patients were cT2 stage and 88.2% treated with concurrent or sequential anthracycline plus taxane preoperatively. SLNB was successfully performed in 169 (94.9%) patients. The mean number of sentinel and regional nodes retrieved was 2.1 ± 1.6 and 12.8 ± 6.3, respectively. Tumoral non-responder and extensive residual nodal disease were significantly associated with detection failure of SLNB. Conversion to node-negative disease was noted in 69 (40.8%) patients. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0%, 22.0%, 75.8%, and 87.0%, respectively and diagnostic performance increased when ≥ 3 sentinel nodes were evaluated. By logistic regression model, tumoral and nodal responder, absent lymphovascular invasion (LVI), estrogen receptor (ER)-negativity, and HER2-positivity were significantly associated with node-negative disease after NCT. Area under the receiver operating characteristic curve increased from 0.890 to 0.949 when considering radiologic-pathologic factors and FNR was the lowest value of 14.3% in 46 patients with tumoral responder, absent LVI, and ER-negative tumor.
Conclusions: SLNB was technically feasible but solely showed higher FNR in this study. Improved diagnostic performance of SLNB combined with radiologic-pathologic characteristics suggests possible clinical value of SLNB after NCT in highly selected patients with node metastasis at diagnosis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-23.
Abstract P1-01-24: Which combinations are helpful to predict axillary lymph node metastasis in T1 breast cancer with ultrasonography and contrast-enhanced MRI and contrast-enhanced 18F-FDG PET-CT?
Authors: Hwang SO , Park HY , Jung JH , Kim WW , Lee YH , Lee JJ , Choi HH , Hwangbo SM 
Published: August 2014

Abstract
Backgrounds: Axillary lymph node(ALN) status has been important factor of treatment and prognosis for patients with breast cancer. Even though the better ultrasonographic instruments have been developed, it is still difficult to predict axillary lymh node metastasis (ALNM) with only ultrasonography(US) in T1 breast cancers which most of newly diagnosed breast cancers are recently since T1 breast cancers have low rate and less tumor burden of ALNM. This study evaluated the accuracy of prediction of ALNM in T1 breast cancer with US, contrast-enhanced MRI (cMRI) and contrast-enhanced 18F-FDG PET/CT (cPET/CT) and found out adequate combinations of these modalities.
Method: Retrospectively, we reviewed 351 breast cancer patients with tumors(T1) ≤2cm in size between January 2008 and December 2011 who were preoperatively examined with US, cMRI, and cPET/CT and underwent pathologic evaluation of axillary lymph nodes acquired by sentinel lymph node biopsy or axillary dissection.

Results: 94(26.8%) patients of 351 had ALNM. The sensitivity, specificity, positive predictive value(PPV), negative predictive value (NPV), and accuracy of ALNM with US were 0.457, 0.887, 0.597, 0.817, 0.772, respectively. cMRI had similar results with US. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of ALNM with cPET/CT were 0.447, 0.942, 0.737, 0.823, 0.809, respectively. The sensitivity if any one or more modalities were suspicious was 0.563. The specificity if all modalities were suspicious was 0.992. The PPV if cMRI and cPET/CT were suspicious was highest than if other combinations were suspicious.
Conclusion: US, cMRI, and cPET/CT are helpful in prediction of ALNM of T1 breast cancers. However, there are no definite modality and combination of modalites to predict ALNM of T1 breast cancers.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-24.
Abstract P1-01-28: What is the actual impact of micrometastases in sentinel lymph nodes in regards to global survival and disease free survival
Authors: Barbosa EM , Araujo Neto JT , Filho EC , Infante KP , Felzener MM , Matielle CR , Modesto MG , Basso R , Goes JCS 
Published: August 2014

Abstract
OBJECTIVE: Assess the clinical relevance of micro metastasis in sentinel lymph nodes in the overall survival and disease free survival of 1,211 patients undergoing sentinel lymph node biopsy.
METHODS: Retrospective cohort study including 1,211 patients undergoing consecutive SLB from 1998 to 2010. SLB were performed in patients with invasive carcinoma of the breast with clinically negative axilla. Age, tumor size, and histologic grades, estrogen and progesterone receptors expression, HER-2, lymphovascular invasion and size of metastases in lymph nodes were assessed. Tumor sizes were divided according to pathologic staging into pT1(&lt; 2,0mm) and pT2(&gt;2,0mm). Lymph nodes were classified as negative (pN0), positive with micro metastases with diameter ranging from 0,21mm to 2,0mm(pN1mi) and positive with macro metastases with diameter greater than 2,0mm(pN1). Statistical analyses were performed by the Likelihood ratio test or Chi-square test for insufficient samples between macro metastases and micro metastases in SLB. Time was considered in months and the overall follow-up time was 125 months and mean time was 65 months. Local regional and distant recurrences were considered as events for disease free survival and Kaplan-Meier survival functions were constructed, testing time between metastases sizes in SLB using the Log-rank test, with a significance level of 5%.
RESULTS: Of the studied variables, lymphovascular invasion(p = 0,068) and local regional and distant metastases(p = 0,002) had a statistically significant association with overall survival. Tumor size(p = 0,016); lymph vascular invasion(p = 0,002) and metastases types in sentinel lymph node(p &lt; 0,001) were associated to disease free survival. In the association tests with types of metastases in sentinel lymph node, the following were statistically significant: age(p = 0,004), tumor size(p &lt; 0,001), lymph vascular invasion(p &lt; 0,001) and local regional and distant recurrences. In the interim and final Cox regression analysis, macro metastases were the only statistically relevant factor for disease free survival(p &lt; 0,001).
CONCLUSION: The presence of micro metastases(pN1mi) in sentinel lymph node is associated to a prognosis similar to that of negative axilla patients(pN0), indicating that other risk factors for local regional and systemic recurrences should be taken into account.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-28.
Abstract P1-04-02: The role of the mTORC1/S6K1 signaling pathway in ER-positive breast cancer.
Authors: Holz MK , Unger HA , Sedletcaia A 
Published: August 2014

Abstract
The mammalian target of rapamycin complex 1 (mTORC1) is a central signaling node in mediating cellular responses to mitogens, hormones and nutrients. The 40S ribosomal S6 kinase 1 (S6K1) is a conserved serine/threonine protein kinase that belongs to the AGC family of protein kinases, which also includes Akt, RSK and many others. S6K1 is the principal kinase effector downstream mTORC1. S6K1 is sensitive to a wide range of signaling inputs, including growth factors, amino acids, energy levels, and hypoxia. S6K1 relays these signals to regulate a growing list of substrates and interacting proteins in control of oncogenic processes, such as cell growth and proliferation, cell survival and apoptosis, and cell migration and invasion.
Growing evidence indicates that there exists a close interaction between the mTORC1/S6K1 pathway and estrogen receptor (ER) signaling. Notably, endocrine resistance is often associated with ligand-independent activation of ERα signaling due to hyperactivation of the mTORC1 signaling pathway, and can be reversed by the mTORC1 inhibitor everolimus in vitro.
Several lines of evidence suggest an important role for S6K1 in ER-positive breast cancer. We demonstrated that S6K1 directly phosphorylates ERα on Ser167, leading to activation of its transcriptional activity. While the MAPK-regulated p90 RSK also contributes to phosphorylation of this site, its contribution is early and transient, while the phosphorylation of Ser167 by S6K1 is prolonged and sustained. Intriguingly, we also found that S6K1 expression is estrogenically regulated. This regulation involves the transcription factor GATA-3 and others. Thus it appears that S6K1 expression is maintained in two modes: a basal level of expression, typical of normal cells, and an estrogen/ERα-dependent specific upregulation. Therefore, there exists a feed-forward regulatory loop whereby S6K1 activates ERα transcriptional activity, leading to increased expression of S6K1. This finding is of great interest since it not only sheds light on the mode of transcriptional regulation of S6K1 expression, but may help understand the role of S6K1 overexpression and activation in the development and progression of breast cancer.
Therefore, hyperactivation of mTORC1/S6K1 signaling may be closely related to ER-positive status in breast cancer, and may be utilized as a marker for prognosis and a therapeutic target.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-04-02.
Abstract P1-05-13: CLIC3 is associated with invasive behaviour and poorer prognosis in estrogen receptor-negative breast cancer.
Authors: Macpherson IR , Dozynkiewicz M , Kalna G , Speirs C , Chaudhary S , Edwards J , Timpson P , Norman J 
Published: August 2014

Abstract
Background: We previously described a Chloride Intracellular Channel-3 (CLIC3)-dependent recycling pathway which trafficked active integrins from late endosomes to the cell surface and which was required for the migratory and invasive behaviour of A2780 ovarian cancer cells in vitro. We also demonstrated that elevated expression of CLIC3 was associated with poor prognosis in pancreatic cancer. We therefore set out to investigate the role of CLIC3 in breast cancer.
Materials and Methods: CLIC3 expression was assessed by immunohistochemistry and the weighted histoscore method in a tissue microarray (TMA) consisting of triplicate cores from 141 patients diagnosed with invasive estrogen receptor (ER)-negative early breast carcinoma between 1995 and 1998. Full clinicopathological and follow-up data were available. Further data were obtained from publicly available gene expression datasets (Desmedt, GSE7390) and Oncomine™. Knockdown of CLIC3 in the ER-ve MDA-MB231 breast cancer cell line was achieved by nucleofection of 2 different siRNA sequences (Dharmacon). Inverse invasion assays measured invasion into a plug of matrigel supplemented with fibronectin over 72 hours whilst organotypic invasion assays measured invasion into a fibroblast-containing collagen matrix over 6 days.
Results: CLIC3 mRNA expression was significantly elevated in breast cancer in comparison to normal breast tissue in two independent data sets. High CLIC3 protein levels were associated with significantly shorter breast cancer specific survival (p = 0.026) in a TMA of 141 ER-ve patients. This finding was corroborated by the observation that high CLIC3 mRNA levels were associated with shorter overall survival in 198 patients in the Desmedt dataset (p = 0.038). Transient silencing of CLIC3 expression using two independent siRNA sequences had no effect on proliferation of MDA-MB231 cells but significantly reduced their invasiveness by 46% and 93% respectively in an inverse invasion assay and by 36% and 42% respectively in an organotypic invasion assay. CLIC3 was found to co-localise with Rab7 and LAMP1 in late endosomes/lysosomes in MDA-MB231 cells.
Conclusions: Our clinical and in vitro data indicate an important role for CLIC3 in the invasive and metastatic behaviour of some breast cancers. Further work to elucidate molecular mechanisms is underway and will be presented.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-05-13.