Despite the success of endocrine therapy for estrogen receptor α positive (ER+) breast cancer, most patients develop resistance to therapy.Understanding the mechanisms regulating estrogen receptor (ER) function in breast cancer is imperative for rationale design of novel therapeutic combinations that will improve efficacy and overcome endocrine therapy resistance.Phosphorylation of ERα markedly regulates receptor function following endocrine therapies such as tamoxifen, implicating receptor phosphorylation as a therapeutic target for modulating therapeutic efficacy.