Abstract SP087: Epigenetic therapy against high-risk breast cancer

Abstract

Standard-of-care therapy in high-risk stage II-III ER+/HER2-negative and Triple-Negative Breast Cancer (TNBC) includes neoadjuvant chemotherapy (NAC) prior to surgery, which is then followed by adjuvant endocrine (for ER+) +/- salvage chemotherapy (for TNBC). These treatments are delivered with limited stratification by disease histology and, while many patients are cured, more than one third of those in whom invasive disease remains in the breast at the time of surgery experience early relapses of metastatic disease within the first few years. The poor survival rate stems from incomplete response to NAC and the lack of alternative tailored therapy against the chemo-resistant disease that recurs. Hence, there is an urgent need for new therapies to treat recurrence and improve outcome. Tumor progression following standard-of-care therapy arises from pre-existing resistant and/or adapting persister cancer cells committing to an expansion phase. These differ from treatment sensitive cells in the epigenetic landscape of their genome, regulating the on/off state of genes for instance. This underlies epigenetic variants, akin to genetic variants, that define vulnerabilities to new treatment strategies. Here, we demonstrate the value of epigenetic therapy in preclinical settings against high-risk breast cancer, putting forward new treatment options to be tested in clinical trials. Citation Format: M Lupien. Epigenetic therapy against high-risk breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP087.