Abstract
Subclonal evolution during primary breast cancer treatment is largely unexplored. We performed whole exome sequencing of tumor biopsies extracted before and after sequential epirubicin and docetaxel in 51 patients included in a neoadjuvant phase II trial. There was a profound and differential redistribution of subclones during epirubicin and docetaxel treatment. While trunk mutations and main subclones persisted, smaller subclones frequently appeared or disappeared during treatment. Reassessment of raw data, beyond formal mutation calling, indicated that the majority of subclones appearing during treatment were present in pretreatment breast cancers below conventional detection limits. No single mutations or mutational profiles predictive of treatment response were identified. A significant drop in tumor mutational burden (TMB) was observed in epirubicin responders (p=0.043), whereas subsequent docetaxel treatment decreased TMB among non-responders (p=0.006). Copy number analysis demonstrated specific genomic regions to be systematically lost or gained during treatment with each compound.
Dr. Andreas Venizelos
FIELD APPLICATIONS SCIENTIST @ OXFORD NANOPORE TECHNOLOGIES
My research interests include genomic alterations and subclonal evolution dynamics in tumours, as well as the genomic profiling of a hitherto understudied cancer type, gastroenteropancreatic neuroendocrine carcinomas (NECs).