Biomarker (panels), either analysed by immunohistochemistry, expression arrays, qRT-PCR or nCounter have been developed. In recent years, it became evident that biomarkers based on tumour biology may have additional value in predicting patient outcome when combined with parameters that merely reflect anatomical issues. For this purpose, nomograms such as the UK-based PREDICT tool or the recently renewed new adjuvant online website may be used to support the shared decision-making process. In daily practice, the risk of recurrence and the need of adjuvant systemic therapy are generally established by considering factors such as nodal status, tumour size, histological grade and/or KI-67, HER2 status and hormone receptor status. However, although much has been achieved, the risk of recurrence persists despite the use of adjuvant endocrine therapy with an annual hazard of recurrence for post-menopausal patients of 2–3% from 10 to 20 years after diagnosis. Treating patients with 5 years of aromatase inhibitor or with 2 to 3 years of tamoxifen followed by aromatase inhibitor (sequential therapy) results in a further reduction of 5-year recurrence rates with 30% compared to tamoxifen alone. In the overviews from the Early Breast Cancer Trialist Collaborative Group (EBCTCG) for hormone receptor-positive breast cancer, it was shown that 5 years of adjuvant tamoxifen therapy reduces the risk of breast cancer recurrence by approximately 40%. The improved outcome can be explained by increased early detection in national screening programmes as well as improved systemic treatment options. In addition to the usual clinical risk factors, the results of this study may identify predictors of high recurrence risk in hormone receptor-positive breast cancer patients treated with sequential tamoxifen and aromatase inhibitor therapy.īreast cancer is one of the leading causes of cancer-related death for women, although mortality has steadily decreased over the last decade. This study was designed to avoid common pitfalls in marker discovery studies such as selection bias, confounding and lack of reproducibility. The trans-DATA study uses a cohort derived from a clinical randomised trial. Selected candidate genes will subsequently be validated in the remaining patients using qMSP. Differentially methylated regions of interest will be selected based on Akaike’s Information Criterion, Gene Ontology Analysis and correlation between methylation and expression levels.
A genome-wide DNA methylation discovery assay will be performed on 60 patients that had a distant recurrence and 60 patients that did not have a distant recurrence using the Infinium Methylation EPIC Bead Chip platform.
Primary breast tumour tissue will be collected, subtyped and used for DNA isolation. Patients from the DATA study are included in the trans-DATA study. The trans-DATA study is a translational sub-study aiming to identify DNA methylation markers prognostic of patient outcome. However, subgroup analysis showed post hoc statistically significant benefits in certain sub-populations. This study found no statistically significant effect of prolonged aromatase therapy. The effect of extended adjuvant aromatase inhibition in hormone-positive breast cancer after sequential tamoxifen, aromatase inhibitor treatment of 5 years was recently investigated by the DATA study.
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