Abstract P4-21-21: Her2 is not a cancer subtype but rather a driver found in all intrinsic subtypes and highly enriched in molecular apocrine tumors

Abstract Her2-enriched (Her2E) breast tumors defined by molecular profiling are discrepant from Her2-amplified tumors defined by clinical assessment – over half of all Her2-amplified tumors are not Her2E, while one-third of Her2E tumors are not Her2-amplified. We explored this discordance using genomic profiles of 4,000 breast tumors. We find clear support that Her2 amplification is a discrete cancer driver event and not a subtype, with little genomic impact other than in expression of genes on the amplicon. Many Her2-amplified tumors clearly belong to the basal, luminal A, or luminal B subtypes. After accounting for the Her2 amplicon, most tumors classified as Her2E appear to be molecular apocrine, expressing high levels of androgen receptor and low to moderate levels of ER. The high rate of Her2 amplification in this group (63%) suggests that additional growth drivers are required for molecular apocrine tumors. Her2 amplification is also a driver across subtypes of several non-breast tumor types. Her2 is amplified in 2% of 5,400 non-breast tumors, spanning 23 tumor types. The Her2 region in non-breast cancers shows a similar range of amplification and breadth of the amplicon, and a comparable rate of overexpression of genes within the amplicon for most Her2A tumors. These discoveries reveal therapeutic opportunities for combining anti-Her2 therapy with endocrine or anti-androgen agents for breast cancer, and for expanding anti-Her2 therapy to other tumor types. Citation Format: Daemen A, Manning G. Her2 is not a cancer subtype but rather a driver found in all intrinsic subtypes and highly enriched in molecular apocrine tumors [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-21.