bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD02-08: Development of DNA Aptamers That Inhibit Invasion, Migration, and Growth of Breast Cancer Cells
Authors: Kopco RL , Iida J , Lehman JR , Somiari S , Somiari R , Mural RJ , Shriver CD. 
Published: April 2011

Abstract
Triple negative (TN) breast cancers are defined by a lack of expression of estrogen, progesterone, and her-2/neu receptors. It is widely recognized that TN breast cancers have a poorer prognosis than other subtypes of breast caner. Given the lack of effective targeted therapies for TN breast cancer patients, understanding of the mechanisms of growth and invasion of these tumors will provide insight into developing novel approaches to lower the mortality from TN breast cancer.
We utilized three TN breast cancer cell lines (HCC38, HCC1806, HCC1937) as model systems to characterize mechanisms of growth, migration, and invasion. FACS analyses demonstrated that these TN cell lines showed a phenotype of CD44+CD24-/lowepithelial specific antigen (ESA)+. An inhibitory antibody against exon v10 of CD44 significantly inhibited three-dimensional (3D) growth of tumor cells. Importantly, this antibody also inhibited alpha2beta1/alpha3beta1 integrins-mediated migration and invasion into matrigel. These results suggest that CD44 harboring exon 10 facilitates progression and metastasis of TN breast cancer cells in vivo by enhancing growth, migration, and invasion. We also demonstrated that this exon interacts with a cell surface tyrosine kinase,
EphA2. Thus, we hypothesize that CD44 would form a molecular complex with EphA2 through exon v10 on TN breast cancer cells that plays a key role in facilitating invasion and metastasis.
In order to develop novel reagents to inhibit TN breast cancer invasion and metastasis, we have utilized SELEX (systematic evolution of ligands by exponential enrichment) to isolate DNA aptamers that specifically recognize exon v10 of CD44. DNA aptamers are functional molecules with the appropriate sequence and structure to form a complex with a target molecule. Typically, dissociation constants for these aptamer-target complexes are in the high pico-molar to low nano-molar range, which is comparable to antibodies. Given the fact of the ease of chemical synthesis and modifications of oligonucleotides, DNA aptamers that recognize cancer cells will be easier to develop and have a great impact for the next generation of strategies for cancer detection, diagnosis, and therapy. We describe the development of “function-blocking” DNA aptamers specific for exon v10 of CD44 that inhibits TN breast cancer invasion and metastasis.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD02-08.
Abstract PD04-07: Monitoring Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC) during Neoadjuvant Combination of Trastuzumab and Bevacizumab with Chemotherapy in HER2 Overexpressing Inflammatory Breast Cancer (IBC): An Ancillary Study of BEVERLY 2 Multicenter Phase II Trial
Authors: Pierga J-Y , Bidard F-C , Petit T , Delozier T , Ferrero J-M , Campone M , Gligorov J , Lerebours F , Roche H , Kraemer S , Mathiot C , Viens P. 
Published: April 2011

Abstract
Introduction: CTC detection in peripheral blood is an independent prognostic factor in early breast cancer but with a low detection rate of 10% to 23% of the patients (B. Rack, ASCO 2010, FC Bidard, Ann Oncol 2010). Changes in the HER2 status of CTC compared to the primary tumor have been reported (Riethdorf S CCR 2010). Predictive value of CEC for response to anti-angiogenic agents is debated.
Material and methods: CTC and CEC were detected in 7.5 ml and 4 ml of blood respectively in IBC (T4d) patients enrolled in the phase II multicenter trial, BEVERLY 2. This study is evaluating the efficacy of bevacizumab (15mg/kg q3w given concurrently) in combination with sequential neoadjuvant chemotherapy of 4 cycles of FEC followed by 4 cycles of Docetaxel-Trastuzumab. Bevacizumab was stopped 4 weeks before and reintroduced 4 weeks (w) after mastectomy. All patients had non metastatic IBC and over expressed HER2 (3+ in IHC or FISH +). The CellSearch™ System, combining EpCAM immunomagnetic selection (IMS) followed by anti-cytokeratin (A45B/B3) and anti-HER2 fluorescently staining for CTC and CD146 IMS and CD105 staining for CEC, was used at baseline, before cycle 5, before and after surgery.
Results: From Oct 2008 to Oct 2009, 52 patients were included in this study and 51 were evaluable for CTC. At baseline, 18 patients out of 51 had ≥ one detectable CTC (35.3%, 95%CI 22-48%, range 1 to 92).
Pathological complete response rate according to local review was 33/47 (70%) or 15/22 (68%) for centrally reviewed cases. At baseline, CTC level was not correlated with CEC level, neither with other patients and tumor characteristics’ (age, nodal status, PeV) nor pCR (centrally reviewed in
24). All positive cases for CTC detection had HER2 positive CTC. Five pts out of 18 (28%) had both HER2+ and HER2 negative CTCs in their blood. A lower level of CEC (&lt; 20/4ml) before C5 could be associated with a higher probability of pCR (Khi2 test, p=0.053). Conclusion: We observed a high CTC detection rate of 35% in this population of patients with HER2+ IBC and a dramatic drop in CTC level during treatment in concordance with the high efficiency of this combination of chemotherapy and targeted therapy. We observed heterogeneity in the HER2 status of CTC in some patients. CEC levels increased progressively during neoadjuvant treatment and decreased after its interruption. Longer follow-up will show if CTC and CEC variations are early predictive factors for this highly efficient combination in HER2+ IBC.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-07.
Abstract PD05-07: Use of Natural ER Beta Modulators in Treating Hormonal Therapy Resistant Breast Tumors
Authors: Ganapathy M , Hareesh NB , Kirma NB , Tagliaferri M , Cohen I , Krishnegowda N , Vadalamudi RK , Tekmal RR. 
Published: April 2011

Abstract
Although systemic hormone therapies that either block local estrogen production by aromatase inhibitors (AI) such as letrozole or block actions of estrogen/ER actions by anti-estrogens (AEs) like tamoxifen are well tolerated, unfortunately, essentially all breast cancers in women with advanced breast cancer develop resistance to these two classes of agents, and the benefit of adjuvant therapy (where micrometastatic disease is present but cannot be directly observed) is also limited by the development of resistance. In addition, side effects associated with the systemic inhibition of aromatase with current compounds limits their long-term utility of them as chemopreventative agents. We have investigated whether treatment of letrozole resistant breast cancer cells with selective plant-derived ER beta agonists (Liquiritigenin; LIQ or Nyasol; NYA) alone or in combination with letrozole affects the growth of AI resistant breast cancer cells, thereby restores sensitivity to AI. To test whether combination therapy restores sensitivity to letrozole, we have treated letrozole resistant breast cancer cells [LTLTca, derived from MCF-7-aromatase tumors resistant to letrozole] with either letrozole alone or with a combination of letrozole and LIQ/NYA. In addition, effects of these compounds on cell growth was also tested using different breast cancer cells including MCF-7, MCF-7-aromatase, ZR-75-1, ZR-75-aromatase, MDA-MB-231 along with tamoxifen resistant MCF-7 or MCF-7- PELP/ZR-75-PELP1. Compared to single agents, combination treatment not only restored sensitivity to letrozole but also resulted in decreased cell proliferation and increased apoptosis as well as increased ERα and decreased ERα levels in resistant cells. Combination of LIQ or NYA not only diminished cell growth in MCF-7-HER2, MCF-7-PELP1, and SKBR-3 breast cancer cells (that express endogenous aromatase) but also affected the expression of aromatase. Detailed investigations indicated that LIQ/NYA affects the induction of aromatase by specifically inhibiting breast cancer specific aromatase promoter 1.3 as well as its activity through inflammatory cytokine-mediated actions. These studies suggest the therapeutic benefit of LIQ or NYA ERα agonist to resensitize breast cancer cells that are resistant to AEs or AI and their ability to selectively inhibit tumor induction of aromatase. Our study suggests a novel role of natural ER beta agonists as valuable therapeutic modulators to treat endocrine sensitive as well as resistant tumors. (Supported by V-Foundation & P30 CA 54174, RRT)
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD05-07.
Abstract PD05-08: Lack of Significant Association between CYP2D6 Polymorphisms and Clinical Outcomes of Adjuvnt Tamoxifen Therapy
Authors: Kim H , Shin H-C , Yom CK , Ahn S , Moon H-G , Han W , Noh D-Y. 
Published: April 2011

Abstract
Purpose: CYP2D6 variant alleles have been suspected to influence on the clinical efficacy of tamoxifen because CYP2D6 is an enzyme which metabolizes tamoxifen into its active forms, endoxifen and 4-hydroxytomoxifen. This study was performed to investigate the correlation between the polymorphisms in CYP2D6 and the clinical outcome of patients receiving tamoxifen. Methods: Between April 2001 and February 2010, 481 patients with hormone receptor-positive, invasive breast cancer receiving tamoxifen monotherapy in Seoul National University Hospital were studied. we analyzed the patients’ CYP2D6 alleles with the technique of PCR and SNaPshot using the blood samples cultured just before the every surgery and investigated the relationships of allelic variants of CYP2D6 to the disease-free survival by the Kaplan-Meier method and Log rank test Results: Each part of all patients’ alleles was genotyped into CYP2D6*1, CYP2D6*2, CYP2D6*5, CYP2D6*10, CYP2D6*41 and All the patients were categorized into 3 types, i.e. 51 homogenous wild type patients, 217 heterogenous variant type ones and 213 homogenous variant type ones according to their allelic types. There was no difference in age, pT, pN, follow up period among these patients. The rate of events which is defined as locoreginal metastasis, distant metastasis, contralateral breast cancer was 7.1%(34 patients totally). Only 2 patients were died due to pulmonary complication with distant metastasis. The number of variant alleles were not associated with the disease free survival.(P = .162; 95% CI in patients with one variant allele vs patients without variant allele and P = .215; 95% CI in patients with two variant alleles vs patients without variant allele) And the number of non-functional alleles were not associated with the disease free survival either.(P = .171; 95% CI in patients with one non-functional allele(CYP2D6*5, CYP2D6*10, CYP2D6*41) vs patients with two functional alleles(CYP2D6*1, CYP2D6*2) and P = .187; 95% CI in patients with two non-functional alleles vs patients with two functional alleles) Even in the subgroups of stage I, stage II or more, premenopause, and postmenopause, there was no difference found in disease free survival. Conclusion: Out results suggest the clinical outcome of the patients who are receiving tamoxifen therapy is independent of the patients’ polymorphisms in CYP2D6 and need more sophisticated investigation into the relationship of the process metabolizing tomoxifen to the clinical effect in the patient's body. Key Words: tomoxifen, CYP2D6, polymorphism
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD05-08.
Abstract PD06-06: Novel Surgical Technique To Assess the Response of Metastatic Axillary Lymph Nodes to Neoadjuvant Chemotherapy in Breast Cancer Patients
Authors: Vrancken Peeters M-JTFD , Straver M , Donker M , Loo C , Wesseling J , Holtkamp M , Rutgers ETJ , Rodenhuis S. 
Published: April 2011

Abstract
Background: An important benefit of neoadjuvant chemotherapy (NAC) is the increase in breast-conserving surgery. At present the response of axillary lymph node metastases to chemotherapy is not assessed accurately, since SN biopsy either before or after NAC will not provide an accurate answer. Therefore a reliable axilla-conserving therapy is not yet a benefit. We developed a new surgical technique to evaluate the axillary nodal response by Marking of the Axillary lymph node with Radioactive Iodine seeds (= the MARI procedure)
Method: Prior to NAC, tumor positive axillary lymph nodes were marked with a Iodine-125 seed under ultrasound guidance (the MARI node). After NAC, the marked lymph node was selectively removed with the use of a gamma-detection probe. A complementary axillary lymph node dissection was performed to assess whether the pathological response in the marked node was indicative for the pathological response in the additional lymph nodes.
Results: In 44 patients who were scheduled for NAC the MARI procedure was attempted. In 42 patients the tumor-positive axillary lymph node was successfully marked with a radioactive Iodine-125 seed. Two patients appeared to have overt distant metastasis and did not undergo complete axillary dissection. Thus, in 40 patients the MARI node was selectively removed after NAC. In all these patients a complementary axillary lymph node dissection was performed. In 24 patients the MARI node contained a macrometastasis after NAC. In 4 patients only isolated tumor cells (ITC) were present in the MARI node. In 24 of these 28 patients further nodal involvement was found. More importantly: in 12 patients (=30%) no residual tumor was present in the MARI node (pathological complete response= pCR) and 10 of them also showed a pCR in the complementary axillary lymph node dissection. In one patient a macrometastasis, and in one, ITC were found in one of the additional nodes. Conclusion: In this study we present the first results of a new surgical technique to assess the response of metastatic lymph nodes in the context of NAC for breast cancer; the MARI procedure. We conclude that marking tumor-positive lymph nodes before NAC and selectively removing them after NAC is feasible. Moreover we report that this MARI node is indicative for the response to NAC in the other axillary nodes: in 30% of the treated patients an axillary pCR was found which was correctly indicated by a negative MARI node in all but one patient. Thus the MARI procedure will enable us to select patients in which axillary lymph node dissection can be avoided after NAC.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-06.
Abstract PD06-10: Clinical Score for Deciding a Sentinel Node Biopsy(SNB) after Neo Adjuvant Treatment(NAC) for Breast Cancer
Authors: Cagnat J , Alran S , Savignioni A , Pierga J-Y , Belichard C , Kirova Y , Salmon RJ. 
Published: April 2011

Abstract
Rationale: Selection of the best candidates for SNB after NAC remains under discussion. A retrospective study identified predictive factors for negative axillary dissection. A score was developed to select patients at high and low risk for metastatic SNB after NAC.
Patients and methods: In 776 patients receiving NAC, clinico biologic patterns were evaluated by a multivariate logistic regression model in order to to predict the negativity of axillary dissection after surgical treatment.
A 4 class score was created using the three significant factors: Initial clinical node status, oestrogen receptors positivity and clinical response to treatment. This model was then prospectively applied tto 180 patients between 2006-8
Results: The probability of having a negative axillary dissection in patients with a score 0, 0-2 and over 2 was respectively 80%, 56% and less than 50%.
Conclusion: We developed a simple and reproducible score to predict the likelihood of having a negative axilla after NAC and consequently to better select the good candidates for SNB after NAC
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-10.
Abstract PD07-05: In Situ Immune Response after Neoadjuvant Chemotherapy for Breast Cancer Predicts Survival
Authors: Ladoire S , Coudert B , Fumoleau P , Arnould L , Ghiringhelli F. 
Published: April 2011

Abstract
Purpose: Accumulating preclinical evidence suggest that anticancer immune responses contribute to the success of chemotherapy. However, the prognostic value of tumor infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival.
Patients and Methods: In a series of 111 consecutive HER2 and a series of 51 non HER2 overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumor infiltration by Foxp3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modeling were used to assess relapse-free survival (RFS) and overall survival (OS). A prognostic scoring system using American Joint Committee on Cancer (AJCC) pathologic staging and immunological markers was created.
Results: Association of high CD8 and low Foxp3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p=0.02) and OS (p=0.002), and outperformed classical prognostic factors in multivariate analysis. A combined score associating CD8/Foxp3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with favorable prognosis in an independent cohort of HER2 negative breast cancer patients.
Conclusion: Immunological CD8 and Foxp3 cell infiltrate after treatment is a novel independent prognostic factor of survival in breast cancer patients treated with neoadjuvant chemotherapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-05.
Abstract PD08-06: Duloxetine for Treatment of Aromatase Inhibitor (AI)-Associated Musculoskeletal Syndrome (AIMSS)
Authors: Henry NL , Banerjee M , Blossom D , Wicha M , Van Poznak C , Smerage JB , Schott AF , Griggs JG , Hayes DF. 
Published: April 2011

Abstract
Background: Approximately 50% of postmenopausal women with hormone receptor positive early stage breast cancer treated with an aromatase inhibitor (AI) develop arthralgias. Standard analgesics are relatively ineffective. Duloxetine is a serotonin and norepinephrine receptor inhibitor with proven efficacy for treatment of multiple chronic pain states. We investigated the hypothesis that duloxetine would be efficacious for treatment of AIMSS.
Methods: We performed a single-arm, open-label phase II study of duloxetine in 35 postmenopausal women who had been treated with AI therapy for at least 2 weeks and who developed new or worsening pain after starting AI therapy that was rated at least 4 on a 10 point Visual Analog Scale. Enrollment was completed in June 2010. Subjects were treated with duloxetine 30 mg daily for one week, and then 60 mg daily for 3 weeks. Depending on patient-perceived response to therapy, patients had the option of continuing duloxetine 60 mg daily or increasing the dose to 60 mg twice daily for the subsequent 4 weeks. Change in patient-reported pain was assessed. Outcome measures included the Brief Pain Inventory (BPI) and modified Health Assessment Questionnaire (HAQ). Benefit from therapy was defined as a 30% decrease in average pain score from baseline to 8 weeks. Paired t tests were used for statistical analysis.
Results: Of the 35 enrolled subjects, 20 subjects completed the 8-week study period, 6 subjects discontinued therapy early because of duloxetine-associated toxicity, and 9 subjects had been enrolled less than 8 weeks at the time of this analysis and were therefore not evaluable. In an intent-to-treat analysis, 16 of 26 evaluable subjects (61.5%) experienced at least a 30% decrease in average pain, and 14 of 20 subjects (70%) who completed all 8 weeks of protocol-directed treatment chose to continue duloxetine therapy. There were statistically significant reductions in average pain severity (p &lt; 0.0001) and maximum pain severity (p &lt; 0.0001) from baseline to 8 weeks. The mean percent reduction in average pain severity between baseline and 8 weeks was 56.1% (95% CI 37.9%-74.2%) and in maximum pain severity was 55.7% (95% CI 37.3%-74.1%). No grade 3 or 4 adverse events were reported. The most common adverse events were fatigue and drowsiness, xerostomia, nausea, and headache.
Conclusions: Duloxetine appears to be effective and well-tolerated for treatment of AIMSS. Final results from the entire cohort will be presented. Future randomized, placebo-controlled studies are warranted. Clinicaltrials. gov NCT01028352.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-06.
Abstract PD08-07: The Impact of 1-Year Supervised Exercise Training on Physical Performance and Quality of Life of Breast Cancer Patients — A Randomise Prospective Phase III Trial
Authors: Saarto T , Penttinen H , Sievänen H , Kellokumpu-Lehtinen P-L , Blomqvist C , Nikander R , Huovinen R , Hakamies-Blomqvist L , Luoma M-L. 
Published: April 2011

Abstract
The BREX study is the largest randomised prospective study to investigate the effect of physical exercise in rehabilitation of breast cancer survivors shortly after adjuvant treatments.Patients: 537 Finnish breast cancer patients(aged 35-68 years) were enrolled into the 1-year aerobic exercise intervention study (BREX) between 2005 and 2007. Patients were randomly allocated into exercise or control group. Methods: The exercise intervention consisted of weekly supervised step aerobics and home training. The physical performance was tested by a 2-km walking test and figure-8 running. The intensity of physical activity was measured by a two-week diary (METs) and Quality of life (QoL)by the EORTC QLQ-C30 and BR-23, FACIT-F and BDI before the intervention and after 6 and 12 mo's. Results: 500/537 patients were included in the final analyses (263 exercise and 237 control group). Patients participated in the supervised weekly exercise training median 32/52 times, vigorous home training 1.6 and endurance 1.4 times per week. Results are shown in table 1 and 2. Conclusions: Supervised aerobic exercise training improved significantly physical performance, even though physical activity increased in both groups. Physical activity correlated positively to QoL during the intervention irrespectively of the study group. However, the intervention itself did not influence on QoL.
Table 1.
Table 2.
Factors association to QoL change from baseline. Change versus change.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-07.