bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-09-33: Validity of Bone Marker Measurements for Monitoring Response to Bisphosphonate (BP) Therapy with Zoledronic Acid (ZOL) in Metastatic Breast Cancer (mBC): Useful or Not?
Authors: Aktas B , Kasimir-Bauer S , Lehmann N , Kimmig R , Kuemmel S. 
Published: April 2011

Abstract
BACKGROUND: Bone is the most common site of metastasis in breast cancer. The detection relies on imaging technology which is costly and can only be performed to a certain degree. Bone markers are noninvasive, inexpensive and potentially might serve as predictive and prognostive surrogate endpoints in detecting bone metastases and response to BPs. This study analyzes the value of the serum markers of type I collagen synthesis (PINP) and degradation (ICTP) as markers of bone metastases in mBC patients (pts) receiving ZOL. The results will be correlated with the levels of CEA and Ca 15-3 as well as the clinical response. MATERIALS AND METHODS: 38 mBC pts (mean age was 60 years: range, 35-86), with confirmed bone metastases who were received chemotherapy and/or hormonal therapy and ZOL iv q 4 wks were participating in our study. 5 ml blood were collected at the time of study start and q 3 months for one year for the analysis of PINP, ICTP, CEA and Ca 15-3 using radioimmunoassays and ECLIA System, respectively. Imaging of bone metastases was performed at the same time points. In this first analysis, data were correlated with the number of bone metastases at study start.
RESULTS: At study baseline, PINP, ICTP, CEA and Ca 15-3 were analyzed in all pts. In 28/38 pts (73%) more than 3 bone metastases were confirmed by imaging and 10/38 pts (27%) presented with 3 or less bone metastases. The median value for ICTP was 6 µg/l (interquartile range 3.9-12.7) and for PINP 58.7 µg/l (43.5-164). Serum PINP and ICTP concentrations were significantly different when pts were stratified into &gt; 3 bone metastases (median value ICTP 6.3 µg/l and PINP 75.3 µg/l) and 3 or less bone metastases (median value ICTP 4.1 µg/l and PINP 47 µg/l), respectively (P&lt;0.05, see Figure 1 for ICTP and 2 for PINP for logarithmized values). No significant differences were seen when tumor marker levels were correlated with the number of bone metastases (P&gt;0.2). Statistical analysis for follow-up measurements will be available after having completed sampling for all 38 pts in 5 months. Up to now, 135 samples of all patients have been analyzed and there seems to be an association between the number of bone metastases, serum levels for PINP/ICTP and response to therapy.
CONCLUSION: In contrast to serum tumor markers, the identification of PINP and ICTP permit to estimate the number of bone metastases and seems to be a useful tool for monitoring mBC pts undergoing BP therapy with ZOL for treatment of bone metastases. These results have to be confirmed in a larger prospective trial.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-33.
Abstract P2-09-38: Role of Oncotype 21 Gene Assay and Adjuvant! Online in Breast Cancer Adjuvant Treatment Decisions
Authors: Khalil DN , Schneider JG 
Published: April 2011

Abstract
Background: Based upon its validation as both a prognostic and predictive tool, the Oncotype 21 gene RS has been broadly adopted into clinical practice, but little has been reported on how RS actually influences clinical decision making in practice.
Methods: A retrospective chart review was performed on all patients for whom a RS was requested within a single faculty practice since the RS became commercially available in 2005. Data were collected to identify: (1) reasons for requesting RS; (2) reasons for RS cancellations; (3) traditional recurrence risk factors enabling alternative prognostic calculations including the Nottingham Prognostic Index and Adjuvant! Online (AOL) web based instrument; and (4) actual adjuvant treatment decisions. Clinician interviews were performed to confirm RS influence on clinician practice and to compare hypothetical and actual treatment decisions.
Results: 109 RS were requested by five different clinicians. 87 RS were obtained on ER+, node-negative patients. The 10-year relapse risk predicted by RS versus that predicted by AOL is plotted in Figure 1 where the actual adjuvant treatment decision is coded and lines are introduced to separate low, intermediate and high risk groups. In patients with a low RS for whom a treatment decision was made, only 1 of 17 (6%) with an intermediate AOL relapse rate, and 4 of 21 (19%) with a high AOL relapse rate, were treated with chemotherapy. These data suggest that a favorable RS recurrence rate influenced the decision not to initiate chemotherapy when the AOL-predicted relapse rate was less favorable. Two distinct areas of “clinical equipoise” were identified where the combination of AOL and RS risks left clinicians ambivalent about the use of adjuvant chemotherapy (AOL 23-26 with RS 11-15, and AOL 29-43 with RS 5-11). Apparent inconsistencies between RS and adjuvant treatment decisions as well as alternative reasons for obtaining RS were identified and reviewed with the treating clinicians. Conclusions: This single institution experience indicates appropriate use of RS in adjuvant ER+ node-negative breast cancer. The predominant effect in this group was to reduce the utilization of adjuvant chemotherapy in patients with intermediate and high relapse risk predicted by conventional prognostic factors. Figure available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-38.
Abstract P2-14-11: Vitamin D Deficiency in Post-Menopausal Breast Cancer Survivors
Authors: Friedman CF , DeMichele A , Su HI , Feng R , Kapoor S , Desai K , Mao JJ. 
Published: April 2011

Abstract
Background: Breast cancer patients on aromatase inhibitors (AIs) are at an increased risk for decreased bone density and fractures. Given the important role vitamin D plays in bone metabolism, vitamin D deficiency may place these patients at an additional risk. Our objective was to examine the prevalence of and risk factors for vitamin D deficiency in post-menopausal breast cancer survivors (BCS) with current or past AI use. Materials and Methods: We conducted a cross-sectional study. Vitamin D levels were obtained utilizing the Diasorin radioimmunoassay using sera. Multiple logistic regression analyses were performed to identify independent risk factors associated with vitamin D deficiency. Results: In our cohort of 391 post-menopausal women with stage I to III breast cancer on AI therapy, the mean vitamin D level was 35 ng/mL, S.D. 12.49. Vitamin D levels were normally distributed in the cohort. Thirty five percent of women were vitamin D deficient, defined as a level less than 30 ng/mL. In our cohort, 73.4% of the participants had vitamin D supplementation documented in their chart; 26.8% of these women were still vitamin D deficient despite supplementation. Adjusting for demographic and clinical variables, non-white patients were more likely to be vitamin D deficient, adjusted odds ratio (AOR) of 2.00, 95% confidence interval (CI) 1.14-3.51, p=.004. Overweight (AOR 3.07, 95% CI 1.77-5.33, p&lt;.001) and obese (AOR 2.88, 95% CI 1.64-5.06, p&lt;.001) women were also at higher risk. In a second model, adjusting for the same covariates and chart-documented vitamin D supplementation, vitamin D supplementation was associated with lower risk for vitamin D deficiency (AOR .29, 95% CI .17-.48, p&lt;.001). The risk for non-white women (AOR 2.19, 95% CI 1.22-3.89, p=.009) and obese women (AOR 3.21, 95% CI 1.79-5.78, p&lt;.001) were increased after adjusting for vitamin D supplementation. Discussion: Hypovitaminosis D is common in BCS, and those who are non-white or have a BMI greater than 25 are at a higher risk of deficiency. When adjusting for vitamin D supplementation, the discrepancy between normal weight patients and obese patients became even more pronounced, suggesting that standard vitamin D supplementation may not be sufficient for these patients. In light of data linking hypovitaminosis D and bone health, oncologists should consider routine testing with particular attention to non-white or overweight patients, and repleting those patients who are deficient.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-11.
Abstract P2-16-01: Overall Survival Data from SOLTI-0701: A Multinational, Double-Blind, Placebo-Controlled, Randomized Phase 2b Study Evaluating the Oral Combination of Sorafenib and Capecitabine in Patients with Locally Advanced or Metastatic HER2-Negative Breast Cancer
Authors: Gomez P , Roché H , Costa F , Segalla JGM , Pinczowski H , Ciruelos EM , Cabral Filho S , Van Eyll B , Baselga J. 
Published: April 2011

Abstract
Background: Sorafenib (SOR) is an oral multikinase inhibitor with antiangiogenic and antiproliferative activity. We previously reported data from the primary analysis of SOLTI-0701 demonstrating a progressionfree survival (PFS) benefit with the oral regimen of SOR + capecitabine (CAP) vs placebo (PL)+CAP in patients with advanced breast cancer (BC). Here we describe overall survival (OS), a secondary endpoint of SOLTI-0701.
Methods: SOLTI-0701 is a multinational (Brazil, France, Spain) phase 2b study in HER2-negative patients with locally advanced or metastatic BC and ≥1 prior chemo regimen for advanced BC. Patients were randomized (1:1) to receive CAP (1000 mg/m2 po, twice daily [BID], 14 of every 21 days) with PL or SOR (400 mg po, BID). The primary endpoint was PFS. The sample size was estimated at 220 patients based on patient accrual projections and the estimated rate of PFS events. OS analysis was planned after 120 events.
Results: A total of 229 patients were enrolled (115 SOR+CAP and 114 PL+CAP) from August 2007 to December 2008. Treatment arms were balanced for age (mean 55.2 y), ECOG status 0 (68%) and 1 (30%), stage IV disease (91%), and visceral metastases (75%). In the primary analysis, median PFS was 6.4 mo for the SOR arm vs 4.1 mo for the PL arm (hazard ratio 0.58; 95% CI, 0.41-0.81; 1-sided P=0.0006); the most common Grade 3/4 toxicity was hand-foot skin reaction/syndrome (45% vs 13%, respectively); discontinuation of treatment due to adverse events was infrequent (15% vs 7%, respectively). OS data are expected by the 3rd quarter of this year and will be presented, as well as updated safety data. Conclusions: The oral combination of SOR+CAP significantly improved PFS in patients with advanced BC. The regimen was tolerable with a manageable toxicity profile. An ongoing phase 3 registration trial is evaluating the combination of SOR+CAP for advanced BC. The secondary endpoint of OS will better characterize the potential role of SOR in advanced BC as randomized controlled trials thus far have yet to demonstrate any survival benefit with antiangiogenic agents.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-01.
Abstract P2-16-06: Final Overall Survival Results, Including Analysis of Patients with Triple-Negative Disease and Aged ≥70 Years, from the ATHENA Study Evaluating First-Line Bevacizumab-Containing Therapy for Locally Recurrent/Metastatic Breast Cancer
Authors: Pritchard KI , Thomssen C , Pierga J-Y , Cortes-Funes H , Biganzoli L , Guan Z , Manikhas G , Jendiroba D , Uziely B , Boyle F , Jagiello-Gruszfeld A , Van Arkel C , Tung Y , Dunne A-A , Smith IE. 
Published: April 2011

Abstract
Background: First-line bevacizumab combined with chemotherapy significantly improves efficacy versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). ATHENA, a multinational, open-label, single-arm study, further evaluated first-line bevacizumab in combination with standard chemotherapy in patients treated in routine oncology practice.
Patients and methods: Eligible patients had HER2-negative LR/mBC, ECOG performance status 0-2, and had received no prior chemotherapy for LR/mBC. They received bevacizumab 10 mg/kg q2w or 15 mg/kg q3w in combination with taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease progression, unacceptable toxicity, or patient withdrawal. The primary endpoint was safety; secondary endpoints included time to progression (TTP) and overall survival (OS). Results: Between September 2006 and March 2009, 2264 patients began therapy with bevacizumab, combined with single-agent paclitaxel (34%), single-agent docetaxel (33%), taxane-based combination therapy (11%), non-taxane-containing therapy (10%), or sequential chemotherapy (switching chemotherapy regimen before disease progression while continuing on bevacizumab; 12%). After final data cut-off in July 2010, the median duration of follow-up was 20.1 months (range 0.1-43.6 months). Bevacizumab therapy was continued for ≥1 year in 473 patients (21%). The safety profile and median TTP were very similar to those previously reported after median follow-up of 12.7 months and are consistent with findings from randomized phase III trials. Final OS results in the overall population and in clinically important subgroups are reported below for the first time.
Conclusion: Median OS in the overall population is consistent with OS results reported from three randomized phase III trials in the first-line setting (25.2-30.2 months). OS results in subsets of patients with TN disease or aged ≥70 years suggest that bevacizumab-containing therapy is an effective option for these patients, who typically have fewer treatment options available.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-06.
Abstract P2-16-08: Administration of the Novel Antiangiogenic PTC299 in Combination with Aromatase Inhibitors Is Feasible and Shows Antitumor Activity in Metastatic Breast Cancer
Authors: Tiersten A , Schneider BP , Dickler M , Volm M , Speyer J , Novik Y , Lehman R , Callahan LA , Darby CH , Miller LL , Miao H. 
Published: April 2011

Abstract
Background: PTC299 is an investigational new drug that suppresses tumor growth by selective post-transcriptional inhibition of tumor VEGF expression. PTC299 demonstrates antitumor activity in both hormone-receptor-positive (HR+) and-negative (HR-) breast cancer xenograft models and eliminates established tumors in aromatase-overexpressing human breast cancer xenografts when given alone or in combination with letrozole.
Methods: This study is assessing the feasibility of PTC299 administration in combination with aromatase inhibitors (AIs) in women with HR+ metastatic breast cancer and natural or induced post-menopausal levels of ovarian function. Patients already receiving or newly initiating a standard dose of an AI are coadministered 100 mg BID of oral PTC299 continuously until disease progression.
Results: To date, the study has enrolled 24 women with a median [range] age of 57 [26-82] years, ECOG PS of 0 (n=12) or 1 (n=12), to receive PTC299 together with letrozole (n=11), anastrozole (n=6), or exemestane (n=7) for a median [range] duration of ∼16 [3-36] weeks. Combination therapy has been generally well tolerated; AEs have been predominantly Grade 1-2, have usually not been PTC299-related. The most frequent AEs have been headache (25%) and hot flashes (25%). No PTC299 dose reductions or discontinuations due to AEs have occurred. Measures of PTC299 plasma exposure have shown ∼2-fold accumulation, with values reaching steady state by -21 days of treatment; trough values have exceeded those maximally active in xenograft models. Relative to baseline, therapy has been associated with on-study reductions in circulating VEGF concentrations and decreases in tumor perfusion as assessed by DCE-MRI. Antitumor activity includes 3 CRs by PET/CT, 1 PR by PET/CT, and 3 PRs by PET scan. To date, 7/24 (29%) patients have received ≥24 weeks of treatment and 10/24 (42%) patients continue on treatment.
Conclusions: Combining PTC299 100 mg BID with standard AI treatment appears feasible. Safety, exposure, pharmacodynamic, and antitumor activity observations have been encouraging. Supported by a grant award from the Department of Defense
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-08.
Abstract P2-17-01: Phase II Study of Bevacizumab in Combination with Docetaxel and Capecitabine for the First-Line Treatment of Patients with Locally Recurrent or Metastatic Breast Cancer
Authors: Musolino A , Bisagni G , De Matteis A , Nuzzo F , Ardizzoni A , Crinò L , Gamucci T , Passalacqua R , Gnoni R , Boni C. 
Published: April 2011

Abstract
Background: Docetaxel (T; Taxotere) with capecitabine (X) is active against metastatic breast cancer (MBC); bevacizumab (B) has demonstrated efficacy with taxanes in the first-line setting. This study was conducted to assess the efficacy and safety of TX-B in patients (pts) with MBC. Patients and methods: In this single-arm, multicenter phase II study, pts received first-line bevacizumab 15 mg/kg and docetaxel 60 mg/m2 on day 1, plus capecitabine 900 mg/m2 twice per day on days 1-14 every 21 days. The treatment was administrated for 3 cycles and in case of objective response or stable disease at that time, pts were treated with 3 additional cycles. More courses of chemotherapy were administered at Investigator's discretion. Bevacizumab was continued until progressive disease, patient refusal, or unacceptable toxicity. Primary end point was progression-free survival (PFS) and secondary end points were tumor response rate (RR), overall survival (OS), and toxicity.
Results: We report data from the first 30 pts enrolled. Median age was 54 (37-72). Eight (27%) pts had triple-negative disease, while 18 (60%) were hormone-receptor positive. HER2 status was recognized as negative in 25 (84%) pts. TX-B was administered for a median of seven cycles. Five complete and 13 partial responses were observed (overall RR 60%). Median response duration was 12 months. Median OS and PFS were 26 and 11 months, respectively. Grade 3/4 adverse events included tromboembolism (10%), neutropenia (23%), hand-foot syndrome (13%), stomatitis (10%). The median TX doses administered per cycle were 60 mg/m2 and 660 mg/m2, respectively. Ten (33%) pts required dose reductions of docetaxel, while capecitabine dose was reduced in 15 (50%) pts. Results of all the 80 assessable pts entered in the study will be presented at the meeting.
Conclusion: TX-B demonstrated significant activity with an acceptable toxicity profile. Maintenance therapy with B is possible for a long period of stable tumor disease.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-17-01.
Abstract P2-19-01: Modulating Response to Phosphoinositol-3-Kinase/mTOR Inhibition in ER Positive Breast Cancer Cell Lines after Acquired Resistance to Estrogen Deprivation
Authors: Sanchez CG , Crowder RJ , Phommaly C , Ellis MJ. 
Published: April 2011

Abstract
Background: We have recently shown that acquired resistance to aromatase inhibitors (AI) can, in some instances, be reversed low-dose estradiol treatment until progression followed by repeat treatment with an aromatase inhibitor (Ellis, M. JAMA 302:774, 2009). We have also demonstrated that simultaneous inhibition of phosphoinositol-3-kinase (PI3K) and ER (though estrogen deprivation) activates cell death through apoptosis, which is reversed by estradiol, revealing a link between ER activation and the efficacy of PI3 kinase inhibition (Crowder, R. Cancer Res 69:3955, 2009). Consistent with this concept we have also shown that long term estrogen deprived (LTED) cells are co-resistant to both classes of agent (SABCS 2009 Abs#3131). We therefore studied ways to overcome resistance to PI3 kinase inhibitors in LTED cell lines using second line endocrine therapy strategies that could be offered to patients with AI resistant advanced disease.
Methods: ER+ MCF7 and T47D (PIK3CA mutant) cells were cultured in phenol-red free media containing charcoal-stripped serum for 12 months to create long term estrogen deprivation (LTED) variants that mimicked clinical endocrine therapy resistance. A variant of the MCF7 LTED line that regained estrogen-dependent proliferation was created by re-exposure to estradiol for 4 months (MCF7 LTED-R). The effects of the PI3K isoform inhibitor BKM120, the mTOR inhibitor RAD001 and the dual PI3K/mTOR inhibitor BGT226 in MCF7 LTED and T47D LTED were assessed in combination with estrogen deprivation and fulvestrant. MCF7 LTED-R cells were treated with PI3 kinase pathway inhibitors after acute estradiol withdrawal. Apoptosis was measured using TUNEL flow cytometry. Results: MCF7 LTED were resistant to all three PI3 kinase inhibitors, but combination treatment with fulvestrant restored apoptosis to levels seen with parental MCF7 cells after acute estrogen-deprivation. Acute estrogen deprivation in MCF7 LTED-R cells was also effective in restoring an apoptotic response to BGT226. T47D LTED cells, which, unlike MCF7 cells, have markedly down-regulated ER expression, become more sensitive to PI3 kinase monotherapy than the parental T47D cell line, particularly in response to BKM120, and fulvestrant did not increase the apoptotic response.
Conclusions: The MCF7 cell results suggest that PI3 kinase inhibitors will be effective in endocrine therapy resistant advanced breast cancer if these agents are administered with appropriate second line endocrine strategies. Potentially efficacious approaches include fulvestrant combinations and second-line aromatase inhibition, but only after restoration of AI sensitivity with estradiol. The T47D experiments suggest that in the setting of ER+ tumors that lose ER upon disease progression PI3 kinase inhibitors may be very effective.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-19-01.
Abstract P2-19-04: Anti-Jak2 and Breast Cancer Activity of NIM811, a Non-Immunosuppressive Cyclosporine A Analog
Authors: Clevenger CV , Zheng J , Harrington K , Zeng X. 
Published: April 2011

Abstract
Cyclophilin A (CypA) is a member of the immunophilin family of peptidyl prolyl isomerases (PPI) that catalyze the cis-trans interconversion of proline imide bonds of peptides. In this role, cyclophilins have been found to function as signaling switches, regulating the activity of receptors, kinases and transcription factors. The PPI activity of CypA is inhibited by the immunosuppressive drug cyclosporine A (CsA), and in turn the CypA-CsA complex inhibits calcineurin-mediated NFAT activation. Our laboratory has recently demonstrated that CypA is necessary for the prolactin (PRL)-induced activation of Jak2/Stat5 signaling and gene expression (Cancer Res 68:7769, 2008). In addition, we have also shown that CsA inhibits the in vitro and in vivo growth and progression of both ER+ and ER-breast cancer cell lines. Here, we show that the non-immunosuppressive CsA analog NIM811 blocked PRL-stimulated activation of the Jak2/Stat5 pathway, and the kinases AKT and MAPK in T47D cells. NIM811 also inhibited ER+, ER-, and Her2+ breast cancer cell proliferation, survival, motility and anchorage independent growth in a dose-dependent manner. NIM811 inhibited PRL induced gene expression, such as CISH and Cyclin D1. NIM811 also blocked the PRL-induced association between Stat5 and cMyb, and at higher doses, triggered PARP cleavage. In summary, these results indicate that non-immunosuppressive cyclophilin inhibitor NIM811 has significant potential as a novel for breast cancer therapeutic.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-19-04.