Proteomics analysis of tissue samples obtained before and during letrozole treatment in postmenopausal patients with locally advanced breast cancer.

Abstract

Abstract Abstract #3030 Introduction
 We report on the analysis of protein expression in the tumor tissue of postmenopausal patients before and after 4 months of letrozole treatment in the neoadjuvant setting. All patients had ER and/or PGR positive breast cancer and were enrolled in the “FAST-study”. Letrozole was given orally as 2.5 mg once daily. Tumor tissue was obtained by large, open biopsies prior to treatment and during final surgery (in general: mastectomy).
 Methods
 We used paired samples from 13 postmenopausal breast cancer patients. Breast cancer tissue and plasma samples were obtained prior to treatment and after 4 months of therapy with letrozole in the neoadjuvant setting. Thus, all in all 26 tumor samples were used from 13 individual patients. Proteins were extracted from 20-50 mg of breast cancer tissue, labeled with fluorescent dyes and separated using 2-dimensional difference gel electrophoresis (2-D DIGE). After image analysis, differentially expressed proteins (p<0.01, paired T- and Wilcoxon tests) were identified using MALDI tandem mass spectrometry.
 Results and discussion
 The 2-D DIGE based method allowed monitoring of 2000-2500 protein species in each sample. After alignment of all these patterns, around 25 cellular proteins were found to be differentially expressed in the pairwise pre-/post-treatment comparison, along with several plasma proteins. Among these cellular proteins were several reported tumor markers such as stathmin and NDPKA, chaperones such as HSP-60, and members of the annexin family. We are currently investigating the correlation between these proteins and the clinical parameters.
 To our knowledge this is the first report on proteomics analysis comparing samples obtained before and during treatment with a third-generation aromatase inhibitor. The study demonstrates the feasibility of performing a high-resolution proteomics analysis on tumor material derived from needle biopsies and yielded a number of potential markers, which will require further confirmation in a larger population. The results might be useful to elucidate adaptive mechanisms to estrogen suppression in vivo. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3030.