Abstract P1-15-22: Clinicopathological significance of diversity index for c-MYC copy number variation after primary systemic therapy in breast cancer

Abstract

Abstract Background: Chemotherapy can alter tumor cell populations by exerting selection pressure. This study was performed to evaluate the change in Shannon diversity index for c-MYC copy number variation after primary systemic therapy (PST) and its clinical implications in breast cancer patients treated with PST. Materials and Methods: One hundred and forty-four breast cancer patients who had residual disease after anthracycline- or anthracycline and taxane-based PST were included in the study. Associations between Shannon index for c-MYC copy number variation in pre- and post-PST breast cancer samples and clinicopathologic features of tumors as well as patient survival were analyzed. Results: Among the 119 patients with both pre- and post-PST samples available for comparison, 17 (14.3%) underwent change in c-MYC amplification status and 40 (33.6%) in c-MYC copy number gain status with most cases showing positive to negative conversion. In the whole group, Shannon index for c-MYC copy number variation was decreased in post-PST specimens compared to pre-PST specimens. Especially, the chemo-responsive group showed a more significant decrease in Shannon index after PST. However, there was no difference in diversity indices between pre- and post-PST specimens in the chemo-resistant group. c-MYC copy number gain and high Shannon indices for c-MYC copy number variation in both pre- and post-PST specimens were associated with adverse clinicopathologic features of breast cancer. In survival analyses, high Shannon indices for c-MYC copy number variation in post-PST samples as well as pre-PST samples were revealed as an independent prognostic factor for decreased disease-free survival. Upon subgroup analysis according to hormone receptor status, high Shannon indices before and after PST were associated with adverse clinical outcome in hormone receptor-positive group but not in hormone receptor-negative subgroup. Conclusions: These results suggest that a change in Shannon index for c-MYC copy number variation after PST reflects chemo-responsiveness and that Shannon index after PST can be used as a prognostic factor in breast cancer patients who receive PST. Citation Format: Kim G, Chung YR, Kim HJ, Kim M, Ahn S, Park SY. Clinicopathological significance of diversity index for c-MYC copy number variation after primary systemic therapy in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-22.