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题目:: Molecular characterisation of ER+ breast cancer before and during treatment with the aromatase inhibitors, letrozole and anastrozole.
作者:: Urruticoechea(A),Dowsett(M),Mackay(A),Dexter(T),Young(O),Miller(W R),Evans(D B),Dixon(G M)
状态:: 发布时间2016-12-12 , 更新时间 2016-12-12
期刊:: J Clin Oncol
摘要:: 9554 Background: Aromatase inhibitors (AIs) are becoming the preferred initial hormone treatment for ER+ primary breast carcinomas in postmenopausal women. The molecular determinants of response/resistance to AI treatment and the molecular changes underpinning response are unknown. We have therefore assessed whether the effects of withdrawing oestrogen with AIs can identify further important molecular features of these tumours.,Postmenopausal women with primary operable breast cancer were randomised to c.2 weeks pre-surgical treatment with letrozole 2.5mg/d or anastrozole 1mg/d. Biopsies were taken before treatment (core-cut) and at surgery (core-cut or excision) and were snap frozen. RNA was extracted, amplified (linear) and subjected to microarray gene expression profiling using Breakthrough Centre cDNA chips with 17,500 features. Change in Ki67 was measured by immunohistochemistry.,Good quality data was derived from 35 pairs of samples. The genes were filtered down to the c.40% that showed the greatest variability across the whole sample set. Hierarchical clustering of the 70 samples using a number of algorithms resulted in c.50% of the pairs co aggregate. Correlation coefficients between the pairs ranged from 0.40 to 0.92. At a false discovery rate of 1%, 1210 and 986 genes were found to increase and decrease, respectively between the pairs, including some well-known oestrogen-dependent genes (eg. TFF1, TFF3 and CCND1). Some of these genes showed reduced expression in >90% of cases. The number of genes whose expression changed by at least a given threshold was related to the degree of suppression of Ki67. There was no significant difference in the number of genes changing between the 2 treatments. Preliminary analysis indicates that there may be differences in some of the genes changing between the 2 treatments.,This is a novel approach to determining in vivo oestrogen-responsive genes for predicting response, guiding therapy and identifying new therapeutic targets. To date many genes have been identified that show profound and consistent changes in expression. These are candidate biomarkers for benefit from AI treatment. [Table: see text].
语言:: eng
DOI:

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