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Over the past several decades, multiple laboratories have identified numerous mechanisms of antiestrogen resistance expressed by estrogen receptor positive (ER+) breast cancer in the pre-clinical setting.In recent studies, our laboratory has uniquely determined a key role for autophagy in the development of acquired (de novo) antiestrogen resistance in the ER+ MCF-7 breast cancer model [Mol Cancer Ther 2008; 7:2977-87].Our studies showed that blockade of autophagy in ER+ breast cancer cells undergoing antiestrogen therapy led to a robust enhancement of caspase-9 mediated apoptotic cell death.