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Ixabepilone (ixempra), a therapeutic option for locally advanced or metastatic breast cancer.

ABSTRACT: Ixabepilone (Ixempra) is a member of a new class of cytotoxic agents, the epothilones. Epothilones promote tubulin polymerization in vitro and demonstrate antitumor activity. This article reviews the preclinical and clinical data that have led to the approval of ixabepilone for patients with locally advanced or metastatic breast cancer for whom anthracycline and taxane treatments have failed.

SUBMITTER: Egerton N

PROVIDER: S-EPMC2730126 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Ixabepilone (ixempra), a therapeutic option for locally advanced or metastatic breast cancer.

Egerton Nancy N

P & T : a peer-reviewed journal for formulary management 20080901 9

Ixabepilone (Ixempra) is a member of a new class of cytotoxic agents, the epothilones. Epothilones promote tubulin polymerization in vitro and demonstrate antitumor activity. This article reviews the preclinical and clinical data that have led to the approval of ixabepilone for patients with locally advanced or metastatic breast cancer for whom anthracycline and taxane treatments have failed. ...[more]

PMID: 19750031

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Project description:BackgroundMetastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS "pathway" activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine.MethodsIn this study, we analyzed matched pairs of tumor specimens collected from 182 patients who received neoadjuvant systemic therapies (NST). Statistical analyses were conducted to determine whether EGFR/HER2/RAS pathway biomarkers and clinicopathological predictors, alone and in combination, are prognostic in breast cancer.FindingsSIAH and EGFR outperform ER, PR, HER2 and Ki67 as two logical, sensitive and prognostic biomarkers in metastatic breast cancer. We found that increased SIAH and EGFR expression correlated with advanced pathological stage and aggressive molecular subtypes. Both SIAH expression post-NST and NST-induced changes in EGFR expression in invasive mammary tumors are associated with tumor regression and increased survival, whereas ER, PR, and HER2 were not. These results suggest that SIAH and EGFR are two prognostic biomarkers in breast cancer with lymph node metastases.InterpretationThe discovery of incorporating tumor heterogeneity-independent and growth-sensitive RAS pathway biomarkers, SIAH and EGFR, whose altered expression can be used to estimate therapeutic efficacy, detect emergence of resistant clones, forecast tumor regression, differentiate among partial responders, and predict patient survival in the neoadjuvant setting, has a clear clinical implication in personalizing breast cancer therapy.FundingThis work was supported by the Dorothy G. Hoefer Foundation for Breast Cancer Research (A.H. Tang); Center for Innovative Technology (CIT)-Commonwealth Research Commercialization Fund (CRCF) (MF14S-009-LS to A.H. Tang), and National Cancer Institute (CA140550 to A.H. Tang).

Dataset Information

Ixabepilone (ixempra), a therapeutic option for locally advanced or metastatic breast cancer.

Publications

Ixabepilone (ixempra), a therapeutic option for locally advanced or metastatic breast cancer.

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