Breast cancer research and treatment
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Breast Cancer Res. Treat. · Jan 2009
TSC22D1 and PSAP predict clinical outcome of tamoxifen treatment in patients with recurrent breast cancer.
Purpose Two genes, TSC22 domain family, member 1 (TSC22D1) and prosaposin (PSAP) were identified in an in vitro functional screen for genes having a causative role in tamoxifen resistance. These genes were also present in our previously established 81-gene signature for resistance to first-line tamoxifen therapy. The aim of this study was to investigate the predictive value of these genes for tamoxifen therapy failure in patients with recurrent breast cancer. ⋯ In multivariate analysis, patients with high mRNA levels of both genes associated significantly with no clinical benefit (OR = 0.19, 95% CI = 0.06-0.62, P = 0.006) and had the shortest PFS (HR = 2.05, 95% CI = 1.29-3.25, P = 0.002). Conclusion These results confirm our previous in vitro and tumor-related findings and are indicative for the failure of tamoxifen treatment in breast-cancer patients. Both TSC22D1 and PSAP are associated with clinical outcome and may have a functional role in therapy resistance.
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Breast Cancer Res. Treat. · Jan 2009
Comparative StudyComparison of gene expression profiles predicting progression in breast cancer patients treated with tamoxifen.
Molecular signatures that predict outcome in tamoxifen treated breast cancer patients have been identified. For the first time, we compared these response profiles in an independent cohort of (neo)adjuvant systemic treatment naïve breast cancer patients treated with first-line tamoxifen for metastatic disease. ⋯ The 78-gene tamoxifen response profile, the 21-gene set and the HOXB13-IL17BR ratio were all significantly associated with TTP in an independent patient series treated with tamoxifen. The addition of multigene assays to ER (IHC) improves the prediction of outcome in tamoxifen treated patients and deserves incorporation in future clinical studies.
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Breast Cancer Res. Treat. · Dec 2008
Extending the benefits of adjuvant therapy in early HR+ breast cancer.
The benefits of adjuvant tamoxifen are well documented, but therapy is limited to 5 years because of reports of an unfavorable risk: benefit profile in later years. However, the risk of relapse continues beyond the end of therapy. Before the MA.17 trial, no agent given after the standard 5 years of adjuvant tamoxifen had been shown to provide additional benefit, leaving women unprotected against the ongoing risk of late recurrences of breast cancer. ⋯ In subsequent intention-to-treat analyses, the benefit of letrozole persisted, despite a significant proportion of patients in the placebo arm having crossed over onto late extended adjuvant letrozole. In additional pre-unblinding, retrospective analyses derived from the core MA.17 data, the benefits of extended adjuvant letrozole increased with treatment duration, at least upto 4 years, and the efficacy of letrozole appeared to vary in defined patient subgroups. Current data strongly support the use of extended adjuvant letrozole to protect postmenopausal women with HR+ early breast cancer against the risk of late recurrence of disease, and suggest that all women should be considered for letrozole, even if several years have elapsed since tamoxifen was completed.
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Breast Cancer Res. Treat. · Dec 2008
Randomized Controlled TrialA phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses.
Lapatinib is a small molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER2). Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Updated efficacy and initial biomarker results from this trial are reported. ⋯ The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive, advanced breast cancer progressing after treatment with anthracycline-, taxane-, and trastuzumab-based therapy. Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine.