Prediction of hormone response in breast cancer by microarray analysis of sequential tumour biopsies from patients receiving neoadjuvant therapy with letrozole

Abstract

3025 Background: Changes in tumour gene expression may be monitored in sequential biopsies of individual tumours taken during neoadjuvant therapy and analysed by microarray analysis. In the present study, the changes occurring within 10–14 days have been related to clinical and pathological response status assessed after 3 months of treatment. Methods: 69 postmenopausal women with large operable ER-rich breast cancers were treated for 3 months with neoadjuvant letrozole. Clinical response was based on clinical and ultrasound changes; pathological response on histological changes. Cancers were sampled at diagnosis, 10–14 days and 3 months; RNA was extracted and hybridized on Affymetrix HG U133A GeneChips. Results: 43 cases were assessable for response; 33 (77%) responded (>50% reduction in tumour volume) and 30 (70%) had a pathological response. No gene changed with treatment in all cases; however consistent up-regulation of 3 genes and down-regulation of 65 genes occurred in 50 cases. Clustering techniques identified changes in gene expression with treatment and produced groups with distinct patterns of molecular changes. Significant differences were detected between non-responders and responders in 125 genes. Combination of gene changes increased discrimination. Conclusions: Changes in pattern of gene expression can be detected in biopsies taken before and after 14 days treatment with neoadjuvant letrozole. These may elucidate the mechanisms of tumour response and allow early recognition of response/resistance. No significant financial relationships to disclose.