Predicting response and resistance to endocrine therapy

Abstract

Abstract 10.1002/cncr.23187.abs Selection for endocrine therapy requiresthe identification of markers that accurately predict response/resistance.In this report, the authors review their published work and abstractresults from an unpublished study to illustrate the potential ofRNA microarrays from sequential tumor biopsies from patients whowere offered neoadjuvant endocrine therapy treatment to identifythe molecular signatures associated with tumor sensitivity/resistance.Clinical response was assessed by serial ultrasound measurementsin postmenopausal women with large, primary, estrogen receptor-richbreast cancers who received neoadjuvant treatment with letrozolefor 3 months. Tumor RNA from biopsies that were taken before andafter 14 days of treatment was hybridized on Affymetrix U133A chipsto determine expression profiles. Classic estrogen-dependent genesand markers of proliferation were changed with treatment in mosttumors but were poorly associated with clinical response (they frequentlywere changed in letrozole-resistant tumors). Differential expressionpatterns could be used to identify heterogeneity in clinically resistanttumors. The results indicated that molecular profiling of early changeswith letrozole treatment offers the opportunity to distinguish betweenclinically responsive and nonresponsive tumors and provides importantinformation about the heterogeneity of endocrine resistance. Cancer2008. © 2007 American Cancer Society.