Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-12

AUTHORS

Yudi Pawitan, Judith Bjöhle, Lukas Amler, Anna-Lena Borg, Suzanne Egyhazi, Per Hall, Xia Han, Lars Holmberg, Fei Huang, Sigrid Klaar, Edison T Liu, Lance Miller, Hans Nordgren, Alexander Ploner, Kerstin Sandelin, Peter M Shaw, Johanna Smeds, Lambert Skoog, Sara Wedrén, Jonas Bergh

ABSTRACT

INTRODUCTION: Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction. METHODS: We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years. Independent datasets of 76 treated population-derived Swedish patients, 135 untreated population-derived Swedish patients and 78 Dutch patients were used for validation. The inclusion and exclusion criteria for the studies of population-derived Swedish patients were defined. RESULTS: Among the 159 patients, a subset of 64 genes was found to give an optimal separation of patients with good and poor outcomes. Hierarchical clustering revealed three subgroups: patients who did well with therapy, patients who did well without therapy, and patients that failed to benefit from given therapy. The expression profile gave significantly better prognostication (odds ratio, 4.19; P = 0.007) (breast cancer end-points odds ratio, 10.64) compared with the Elston-Ellis histological grading (odds ratio of grade 2 vs 1 and grade 3 vs 1, 2.81 and 3.32 respectively; P = 0.24 and 0.16), tumor stage (odds ratio of stage 2 vs 1 and stage 3 vs 1, 1.11 and 1.28; P = 0.83 and 0.68) and age (odds ratio, 0.11; P = 0.55). The risk groups were consistent and validated in the independent Swedish and Dutch data sets used with 211 and 78 patients, respectively. CONCLUSION: We have identified discriminatory gene expression signatures working both on untreated and systematically treated primary breast cancer patients with the potential to spare them from adjuvant therapy. More... »

PAGES

r953

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/bcr1325

DOI

http://dx.doi.org/10.1186/bcr1325

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023450491

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16280042


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