Abstract 3601A: Concordance of genomic alterations between primary and metastatic matched breast tumors

Cancer therapy exerts a strong selection pressure that shapes tumor evolution. Recent studies have demonstrated high rates of concordance (greater than 80%) between primary tumor and recurrences. The main objective of our study was to demonstrate the molecular evolution of breast cancer using next-generation sequencing (NGS) at initial diagnosis and after metastatic progression beyond at least 1 line of treatment. Methods: We conducted a retrospective analysis of tumors in patients with metastatic breast cancer (MBC). Breast cancer specimens from metastatic sites following at least 1 line of treatment were obtained and analyzed using NGS from an existing prospective molecular profiling study (NCT02416518). Eligible participants from this study had their archival primary tumor specimens obtained and analyzing using the same NGS techniques. Samples were analyzed using Foundation One NGS, evaluating 343 genomic alterations. Concordance of genomic alterations from initial diagnosis to disease progression after metastatic recurrence was the primary endpoint. This study population was from an integrated, community-based healthcare system, serving rural populations primarily in the Dakotas and Minnesota. Results: A total of 10 patients had evaluable primary tumors and matched metastatic specimens. For the 20 tumors evaluable for matched analysis, we found 126 unique gene alterations from the 343 genes assayed, of which 31 (24.6%) were actionable (defined as alterations with established or investigational therapeutics based on literature review). Each tumor had an average of 30.4 alterations (range 15-43) and 7 actionable alterations, (range 0-12). There was only 1 patient that had no actionable alteration in the primary or metastatic tumor. Taking the 10 individual patients into consideration, we found a concordance rate of 64% for all gene alterations and a 61.2% concordance rate for the actionable gene alterations between the two time points. The most common actionable alteration was the activating PIK3CA gene alteration, which had 100% concordance in the 6 patients that had the alteration. The other key actionable alterations with 100% concordance involved the AR, BRCA2, CCND1, CDKN2B, ERBB2, PTEN, and ROS1. Conclusion: Contrasting with prior studies, in our small sample there was moderate concordance of gene alterations between primary and metastatic tumor samples. Despite this, high concordance of key actionable alterations (PIK3CA, PTEN, CCND1, ERBB2) was maintained throughout the disease course. This suggests therapeutic potential early on in the disease course, as key actionable driver mutations are present at diagnosis and persist beyond metastatic disease progression. Citation Format: Anu G. Gaba, Steven F. Powell, Paul A. Thompson, Megan L. Landsverk, Chun-Hung Chan, Jennifer L. Weiss, Lora J. Black, James M. Ford. Concordance of genomic alterations between primary and metastatic matched breast tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3601A.