Abstract 5030: Intra-patient tumor evolution analysis in dogs with many mammary tumors identifies signatures of tumor aggression in early-stage breast cancers

Abstract

Abstract Despite tremendous improvements in breast cancer detection, it remains unclear which early-stage tumors will later become aggressive. Dogs provide a unique opportunity to unravel early-stage tumor evolution, as dogs frequently develop multiple naturally occurring mammary tumors. To identify which early-stage human breast tumors will later become malignant, we analyzed mutational profiles of mammary tumors from two canine cohorts to identify patterns of tumor evolution. We compared our dog tumor signatures with human breast cancers. We found that dogs and humans share many known cancer driver mutations. Additionally, three of the five dogs with at least five mammary tumors had a single driver mutation present in most of their tumors. Despite sharing patient-level exposures and environment, passenger mutations significantly differ between these tumors, suggesting independent primaries initiated by a catalyzing factor causing the same driver mutation in each tumor. However, tumors from the same dog with the same driver gene mutations rarely exhibit the same expression-based breast cancer subtypes. Our analysis highlights the mutational similarities of dog and human breast cancers and provides insight into their development. Citation Format: Kiley Graim. Intra-patient tumor evolution analysis in dogs with many mammary tumors identifies signatures of tumor aggression in early-stage breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5030.