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- Bjohle, J, et al.
(författare)
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Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial
- 2013
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Ingår i: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 139:3, s. 751-758
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum (TM) assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p andlt; 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26-2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum (TM) predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.
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- Hatschek, T, et al.
(författare)
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Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial
- 2012
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Ingår i: Breast Cancer Research and Treatment. - New York, USA : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 131:3, s. 939-947
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Tidskriftsartikel (refereegranskat)abstract
- Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.
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- Linderholm, B. K., et al.
(författare)
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Angiogenic factors in relation to clinical effect in a phase II trial of weekly paclitaxel
- 2013
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Ingår i: Breast. - : Elsevier BV. - 1532-3080. ; 22:6, s. 1142-1147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several anticancer agents including paclitaxel have an inhibitory effect on angiogenesis. Aims: To compare the overall response rate and time to progression with changes in circulating angiogenic factors during palliative treatment with weekly paclitaxel. Material and methods: Patients with metastatic BC, ECOG 0-2, received weekly paclitaxel, concomitant with trastuzumab if HER2+ BC (n = 7). Circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined at base-line and before start of new course. Results: Fifty-five of 63 included patients were evaluable. The overall response rate including stable disease >= 24 weeks (CR + PD + SD) was obtained in 25 of the evaluable patients (45%). The median time to progression (TTP) was 5.3 months and overall survival (OS) 16.7 months. Patients with triple negative breast cancer (TNBC) showed a trend towards higher base-line VEGF compared with hormone receptor positive or HER2+ tumours and had shorter TTP. Significant differences in VEGF and bFGF levels at 12 weeks were found between patients with longer versus shorter TTP (VEGF: p = 0.046, bFGF: p = 0.005) and between patients gaining versus lacking clinical benefit (VEGF: p = 0.05, bFGF: p = 0.02). Conclusions: The clinical utility of circulating VEGF may be a useful tool for monitoring treatment efficacy. (C) 2013 Elsevier Ltd. All rights reserved.
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| 9. |
- Nemes, Szilard, 1977, et al.
(författare)
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Integrative genomics with mediation analysis in a survival context
- 2013
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Ingår i: Computational and mathematical methods in medicine. - : Hindawi Limited. - 1748-6718 .- 1748-670X. ; 2013, s. 413783-
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Tidskriftsartikel (refereegranskat)abstract
- DNA copy number aberrations (DCNA) and subsequent altered gene expression profiles may have a major impact on tumor initiation, on development, and eventually on recurrence and cancer-specific mortality. However, most methods employed in integrative genomic analysis of the two biological levels, DNA and RNA, do not consider survival time. In the present note, we propose the adoption of a survival analysis-based framework for the integrative analysis of DCNA and mRNA levels to reveal their implication on patient clinical outcome with the prerequisite that the effect of DCNA on survival is mediated by mRNA levels. The specific aim of the paper is to offer a feasible framework to test the DCNA-mRNA-survival pathway. We provide statistical inference algorithms for mediation based on asymptotic results. Furthermore, we illustrate the applicability of the method in an integrative genomic analysis setting by using a breast cancer data set consisting of 141 invasive breast tumors. In addition, we provide implementation in R.
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| 10. |
- Shubbar, Emman, 1974, et al.
(författare)
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Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome.
- 2013
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Breast cancer is a potentially fatal malignancy in females despite the improvement in therapeutic techniques. The identification of novel molecular signatures is needed for earlier detection, monitoring effects of treatment, and predicting prognosis. We have previously used microarray analysis to identify differentially expressed genes in aggressive breast tumors. The purpose of the present study was to investigate the prognostic value of the candidate biomarkers CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 in breast cancer. METHODS: The expression levels and subcellular localization of the CCNB2, ASPM, CDCA7, KIAA0101, and SLC27A2 proteins were measured using immunohistochemistry (IHC) on a panel of 80 primary invasive breast tumors. Furthermore, the mRNA levels of CCNB2, KIAA0101, and SLC27A2 were subsequently examined by qRT-PCR to validate IHC results. Patient disease-specific survival (DSS) was evaluated in correlation to protein levels using the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of aberrant protein expression of the candidate biomarkers on patient DSS and to estimate the hazard ratio at 8-year follow-up. RESULTS: Elevated cytoplasmic CCNB2 protein levels were strongly associated with short-term disease-specific survival of breast cancer patients (<= 8 years; P<0.001) and with histological tumor type (P= 0.04). However, no association with other clinicopathological parameters was observed. Multivariate Cox regression analysis specified that CCNB2 protein expression is an independent prognostic marker of DSS in breast cancer. The predictive ability of several classical clinicopathological parameters was improved when used in conjunction with CCNB2 protein expression (C-index = 0.795) in comparison with a model without CCNB2 expression (C-index = 0.698). The protein levels of ASPM, CDCA7, KIAA0101, and SLC27A2 did not correlate with any clinicopathological parameter and had no influence on DSS. However, a significant correlation between the expression of the CCNB2 and ASPM proteins was detected (P = 0.03). CONCLUSION: These findings suggest that cytoplasmic CCNB2 may function as an oncogene and could serve as a potential biomarker of unfavorable prognosis over short-term follow-up in breast cancer.
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