Abstract 822: The molecular diversity of Luminal A breast cancer.

Abstract

Abstract Breast cancer is a collection of diseases with distinct molecular traits, prognosis, and therapeutic options. Luminal A breast cancer is the most heterogeneous, both molecularly and clinically. Using genomic data from nearly 1000 Luminal A tumors from multiple studies, we identified at least four major subtypes defined by distinct copy-number and mutation profiles. Here we show an atypical Luminal A subtype characterized by high genomic instability, TP53 mutations, and increased Aurora kinase signaling. These genomic alterations lead to a worse clinical prognosis. Copy number heterogeneity comes in tandem with distinct mutation spectra. We find a prevalence of PIK3CA, GATA3, and AKT1 mutations in the subtypes characterized by relatively diploid genomes subtypes. Moreover, we highlight a strong association between MAP3K1 mutations and gains and losses of chromosomes 8 and 16. Finally, an unbiased pathway analysis revealed multiple rare, but mutually exclusive, alterations linked to loss of activity of co-repressor complexes N-Cor and SMRT. These rare alterations are prevalent in Luminal A tumors and may predict response to endocrine therapy. Our work shows how comprehensive genomic characterization of tumor subtypes is fundamental to inform clinical trials and to move towards personalized therapies. Figure 1: Luminal A subtypes as determined by copy-number clustering. Citation Format: Ciriello Giovanni, Charles M. Perou, Chris Sander, Nikolaus Schultz. The molecular diversity of Luminal A breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 822. doi:10.1158/1538-7445.AM2013-822 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.