Abstract PL05-01: Heterogeneity in DCIS and invasive breast cancers.

Abstract

Abstract Intratumor genetic and phenotypic heterogeneity of cancer cells underlies tumor progression and therapeutic resistance; thus, it is a major clinical problem. We have characterized intratumor genetic and phenotypic heterogeneity by immunoFISH (iFISH) in DCIS (ductal carcinoma in situ), primary invasive tumors, lymph node and distant metastases, as well as breast tumor biopsies before and after treatment. We found the highest genetic diversity in distant metastases but surprisingly these lesions were less divergent than primary-lymph node pairs. Intratumor diversity was also associated with tumor subtype and response to treatment. We also developed preclinical models to address the functional relevance of intratumor clonal heterogeneity in breast cancer and found cooperative interactions that promote tumor growth and metastatic progression. Our analyses of clonal frequency and drivers of tumor growth have revealed some unexpected findings. Our results emphasize the need to understand the cancer cell populations that compose tumors to be able to predict tumor evolution. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):PL05-01. Citation Format: Kornelia Polyak. Heterogeneity in DCIS and invasive breast cancers. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr PL05-01.