Changes in expression of oestrogen regulated and proliferation genes with neoadjuvant treatment highlight heterogeneity of clinical resistance to the aromatase inhibitor, letrozole.

Breast Cancer Research : BCR
W R Miller, Alexey Larionov

Abstract

Clinical resistance is a major factor limiting benefits to endocrine therapy. Causes of resistance may be diverse and the mechanism of resistance in individual breast cancers is usually unknown. The present study illustrates how changes in the expression of proliferation and oestrogen-regulated genes occurring during neoadjuvant treatment with the aromatase inhibitor, letrozole, may define distinctive tumour subgroups and suggest different mechanisms of resistance in clinically endocrine resistant breast cancers. Postmenopausal women with large primary oestrogen-receptor (ER)-rich breast cancers were treated neoadjuvantly with letrozole (2.5 mg daily) for three months. Clinical response was determined by ultrasound changes in tumour volume. Tumour ribonucleic acid (RNA) from biopsies taken before, after 14 days and after three months of treatment was hybridized on Affymetrix U133A chips. Changes in expression of KIAA0101, TFF3, SERPINA3, IRS-1 and TFF1 were taken as markers of oestrogen regulation and those in CDC2, CKS-2, Cyclin B1, Thymidine Synthetase and PCNA as markers of proliferation. Fifteen tumours with < 50% volume reduction over three months of treatment were classified as being clinically non-responsive. Gene expres...Continue Reading

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Citations

Apr 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Luca MagnaniMathieu Lupien
Jan 27, 2012·Breast Cancer Research : BCR·William R Miller, Alexey A Larionov
Jan 24, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Cynthie Wong, Shiuan Chen
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Datasets Mentioned

BETA
GSE5462
GSE20181

Methods Mentioned

BETA
biopsies
chips
chip
PCR

Software Mentioned

Affymetrix
Primer3

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