Abstract PD4-1: Comparison of mutations and protein expression in potentially actionable targets in 5500 triple negative vs. non-triple negative breast cancers

Abstract Introduction Triple negative breast cancer is a heterogeneous disease with no established targeted treatment options for patients with metastatic disease. Methods A cohort of 5500 patient samples was evaluated for differences and similarities in gene mutation (Sanger or Illumina Truseq), protein expression (immunohistochemistry), and/or amplification/rearrangement (CISH or FISH) between triple negative and non-triple negative breast cancers, with 16% of those patients identified as triple negative by IHC testing. Results PIK3CA and P53 gene mutations, PIK3CA, TOP2A, and EGFR amplification (measured as ≥ 4 copies in 40% or more tumor cells by FISH), and AR, EGFR, SPARC, and TS protein expression were shown to differ between the triple negative and non-triple negative breast cancer patients. The rate of mutation of the P53 tumor suppressor gene, measured by sequencing was twice as high in TNBC patients as in non-TNBC patients (60% versus 30%), while PIK3CA was mutated in half as many TNBC patients (12% versus 31% of non-TNBC patients). Amplification of Her2, PIK3CA, cMYC, and TOP2A was significantly greater in the non-TNBC patient population, while amplification of EGFR was significantly higher in the TNBC patient population (24% versus 13% of non-TNBC patients). Androgen receptor was expressed in 56% of the non-TNBC cohort but in only 15% of the TNBC cohort. Conclusions The gene mutation and protein expression differences in the triple negative subset of breast cancer patients, such as EGFR amplification, SPARC protein expression and P53 gene mutation, could inform new therapeutic possibilities for these difficult to treat, often more aggressive cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD4-1.