Abstract 3386: Molecular profiling of breast cancer organ-specific metastases
Authors: Kimbung Siker , Johansson Ida , Kovács Anikó , Lövgren Kristina , Bergh Jonas , Carlsson Lena , Einbeigi Zakaria , Frostvik-Stolt Marianne , Linderholm Barbro , Lindh Brigitta , Loman Niklas , Malmberg Martin , Sundquist Marie , Söderberg Martin , Walz Thomas , Hatschek Thomas , Fernö Mårten , Hedenfalk Ingrid 
Published: August 2012

Abstract
Background: Breast cancer molecular subtypes preferentially metastasize to specific organs, but the underlying molecular mechanisms are not well understood. While several studies have attempted to delineate these mechanisms by making predictions from primary tumours, the likelihood of missing further relevant biological differences which may be enriched or distinctively present in the metastases cannot be overlooked. In addition, survival after relapse is influenced by the anatomical location of the metastasis, with visceral involvement associated with the poorest survival, suggesting that differences in biology and response to treatment may exist. However, the scarcity of clinical material from metastatic lesions has largely prevented detailed molecular characterization of breast cancer site-specific metastases. Material and Methods: We performed global gene expression profiling on 122 fine needle aspirates of metastatic lesions from different anatomical sites obtained from breast cancer patients treated within the Swedish randomized trial (TEX) of chemotherapy for metastatic breast cancer. Sub-classification was performed using unsupervised hierarchical clustering, while differentially expressed genes and modulated pathways in metastases from different sites and sub-classes were identified using Significance Analysis of Microarrays (SAM) analysis. Breast cancer survival after relapse was also compared between patients. Results: We confirmed the observation that breast cancer metastasis to visceral organs is associated with the poorest outcome. Molecularly, samples were sub-classified into groups with strong correlations with the previously described breast cancer intrinsic subtypes and also striking overlap with pathological characteristics of the primary tumour. Metastasis pairs from the same individual were more similar to each other than to independent metastatic lesions from other patients. More interestingly, liver metastases formed a unique sub-cluster which could be distinguished from the other sites by the expression of several genes (and pathways) involved in focal adhesion, matrix remodelling, and wnt signalling. Conclusions: Our data suggest that breast cancer molecular subtypes and primary tumour characteristics are to a large extent maintained in recurrences and further that liver metastases may be notably different and represent a distinct entity with a separate underlying biology which may hence require specific targeted therapeutic management.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3386. doi:1538-7445.AM2012-3386