show Abstracthide AbstractCombination of CDK4/6 inhibitors and endocrine therapy improves clinical outcomein advanced estrogen receptor (ER)-positive breast cancer, however relapse isinevitable. Human breast cancer cell lines that have undergone long term estrogen deprivation were cultured in 1uM palbociclib until resistance developed. Exome sequencing was undertaken to identify mutations and copy number alterations associated with resistance.