Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial

Hatschek, Thomas; Carlsson, Lena; Einbeigi, Zakaria; Lidbrink, Elisabet; Linderholm, Barbro; Lindh, Birgitta; Loman, Niklas; Malmberg, Martin; Rotstein, Samuel; Söderberg, Martin; Sundquist, M.; Walz, Thomas; Hellström, Mats; Svensson, Harry; Åström, Gunnar; Brandberg, Yvonne; Carstensen, John; Fernö, Mårten; Bergh, Jonas

doi:10.1007/s10549-011-1880-9

Cited by 25 publications

(22 citation statements)

References 26 publications

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“…The estimated HRs (not reported) showed that for many treatments the assumption of proportional hazards is not tenable due to the markedly change of HRs through time, suggesting that the use of this more flexible methodology is more appropriate than the analysis based on the HRs alone. Hatschek [59] 2012 EPI ? PAC Table S2A), the estimates of the difference in the expected PFS/TTP between EXE/EVE versus each single chemotherapy-based treatment are represented.…”

Section: Resultsmentioning

confidence: 99%

A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer

Generali

Venturini

Rognoni

et al. 2015

Breast Cancer Res Treat

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The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods extend standard pairwise meta-analysis to allow simultaneous comparison of multiple treatments while maintaining randomization of individual studies. The method enables "direct" evidence (i.e., evidence from studies directly comparing two interventions) and "indirect" evidence (i.e., evidence from studies that do not compare the two interventions directly) to be pooled under the assumption of evidence consistency. We used NMA to evaluate progression-free survival (PFS) and time to progression (TTP) curves in 34 studies, and response rate (RR) and the hazard ratios (HRs) of the PFS/TTP in 36 studies. A number needed to treat (NNT) analysis was also performed as well as descriptive comparison of reported toxicities. The NMA for PFS/TTP curves and for HR shows EXE/EVE is more efficacious than capecitabine plus sunitinib, CMF, megestrol acetate and tamoxifen, with an average of related-PFS/TTP difference ranging from about 10 months for capecitabine plus sunitinib to more than 6 months for tamoxifen. The NMA for overall RR shows that EXE/EVE provides a better RR than bevacizumab plus capecitabine, capecitabine, capecitabine plus sorafenib, capecitabine plus sunitinib, CMF, gemcitabine plus epirubicin plus paclitaxel, EVE plus tamoxifen, EXE, FEC, megestrol acetate, mitoxantrone, and tamoxifen. Finally, the NMA for NNT shows that EXE/EVE is more beneficial as compared to BMF, capecitabine, capecitabine plus sunitinib, CMF, FEC, megestrol acetate, mitoxantrone, and tamoxifen. The combination of EXE/EVE as first- or second-line therapy for ER+ve/HER2-ve metastatic breast cancer is more efficacious than several chemotherapy regimens that were reported in the literature. Toxicities also favored EXE/EVE in most instances.

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Section: Resultsmentioning

confidence: 99%

A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer

Generali

Venturini

Rognoni

et al. 2015

Breast Cancer Res Treat

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“…The test cohort consisted of 304 women with metastatic breast cancer who were enrolled in a randomized phase III trial conducted between 2002 and 2007 in Sweden, comparing two different first‐line chemotherapy regimens (Hatschek et al., 2012). Patients with brain metastases, HER2 amplified tumors, or other malignancies diagnosed within five years of enrollment were excluded from the trial.…”

Section: Methodsmentioning

confidence: 99%

Claudin‐2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences

et al. 2013

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Keywords:Breast cancer Liver metastasis Claudin-2 Prognostic biomarker A B S T R A C TBackground: Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer.Methods: Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used.Results: CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites. Claudin-2 protein was more frequently expressed in primary tumors from patients who subsequently developed liver metastases (P ¼ 0.02) and high expression was associated with a shorter metastasis-free interval (cohort 1, HR ¼ 1.4, 95% CI ¼ 1.0e1.9; cohort 2, HR ¼ 2.2, 95% CI ¼ 1.3e3.5). Specifically, a significantly shorter interval between primary tumor diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR ¼ 2.3, 95% CI ¼ 1.3e3.9). Conclusion:These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor.ª 2013 Federation of European Biochemical Societies.Published by Elsevier B.V. All rights reserved.Abbreviations: BCSS, breast cancer specific survival; CI, confidence interval; CLDN2, claudin-2 mRNA; ER, estrogen receptor; HR, hazard ratio; IHC, immunohistochemistry; LiMFS, liver metastasis-free survival; LNM, lymph node metastasis; OR, odds ratio; PR, progesterone receptor; RFS, relapse-free survival; TMA, tissue microarray.

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“…The median follow-up for postrecurrence survival was 45 months (range, 9-135 months) for patients alive at last update (July 2013). Detailed information regarding the design and outcome of the trial has been published (22). Fine-needle aspirates (FNA) of at least one metastatic lesion were collected before commencement of treatment whenever possible.…”

Section: Patients and Tumorsmentioning

confidence: 99%

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

Kimbung

Johansson

Danielsson

et al. 2016

Clinical Cancer Research

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in collaboration with the TEX study group Abstract Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis.Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n ¼ 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested.Results: Liver relapse was associated with estrogen receptor (ER) expression (P ¼ 0.002), luminal B subtype (P ¼ 0.01), and was prognostic for an inferior postrelapse survival (P ¼ 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P ¼ 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P ¼ 0.001) among luminal A tumors.Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer.

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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

Cited by 25 publications

References 26 publications

A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer

A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer

Claudin‐2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

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