Using a combination of integrative analysis of primary tumors and functional characterization in in vitro models, we have provided evidence that 1) copy number profiles can alter in a subset of ER-positive breast cancers in response to AI treatment, and 2) distinct copy number aberrations (such as CHKA amplification) can influence the sensitivity of cancer cells to estrogen deprivation, providing evidence to suggest that specific copy-number aberrations may result in resistance to AI therapy. This evidence concerns the gene ESR1 and cancer.