About 20% to 40% of patients with breast cancer eventually develop recurrences in distant organs, which are often not detected until years to decades after the primary tumor diagnosis. This phenomenon is especially pronounced in estrogen receptor-positive (ER(+)) breast cancer, suggesting that ER(+) cancer cells may stay dormant for a protracted period of time, despite adjuvant therapies. Multiple mechanisms have been proposed to explain how cancer cells survive and remain in dormancy, and how they become reactivated and exit dormancy. These mechanisms include angiogenic switch, immunosurveillance, and interaction with extracellular matrix and stromal cells. How to eradicate or suppress these dormant cancer cells remains a major clinical issue because of the lack of knowledge about the biologic and clinical nature of these cells. Herein, we review the clinical manifestation of metastasis dormancy in ER(+) tumors, the current biologic insights regarding tumor dormancy obtained from various experimental models, and the clinical challenges to predict, detect, and treat dormant metastases. We also discuss future research directions toward a better understanding of the biologic mechanisms and clinical management of ER(+) dormant metastasis. ©2013 AACR.
