Erica Dalla1,5, Amulya Sreekumar2,5, Julio A. Aguirre-Ghiso3 and Lewis A. Chodosh2,4 1Division of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Department of Oncological Sciences, Black Family Stem Cell Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA 2Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA 3Department of Cell Biology, Department of Oncology, Cancer Dormancy and Tumor Microenvironment Institute, Montefiore Einstein Cancer Center, Gruss Lipper Biophotonics Center, Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA 4Department of Medicine, Abramson Cancer Center, and 2-PREVENT Translational Center of Excellence, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA Correspondence: julio.aguirre-ghisoeinsteinmed.edu; chodoshpennmedicine.upenn.edu

↵5 These authors contributed equally to this work.

The pattern of delayed recurrence in a subset of breast cancer patients has long been explained by a model that incorporates a variable period of cellular or tumor mass dormancy prior to disease relapse. In this review, we critically evaluate existing data to develop a framework for inferring the existence of dormancy in clinical contexts of breast cancer. We integrate these clinical data with rapidly evolving mechanistic insights into breast cancer dormancy derived from a broad array of genetically engineered mouse models as well as experimental models of metastasis. Finally, we propose actionable interventions and discuss ongoing clinical trials that translate the wealth of knowledge gained in the laboratory to the long-term clinical management of patients at a high risk of developing recurrence.