Emma Nolan1,2, Yibin Kang3,4 and Ilaria Malanchi1 1Tumour Host Interaction laboratory, The Francis Crick Institute, NW1 1AT London, United Kingdom 2Auckland Cancer Society Research Centre, University of Auckland, Auckland 1023, New Zealand 3Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA 4Ludwig Institute for Cancer Research Princeton Branch, Princeton, New Jersey 08544, USA Correspondence: emma.nolanauckland.ac.nz; ykangprinceton.edu; Ilaria.Malanchicrick.ac.uk

Cancer metastasis, or the development of secondary tumors in distant tissues, accounts for the vast majority of fatalities in patients with breast cancer. Breast cancer cells show a striking proclivity to metastasize to distinct organs, specifically the lung, liver, bone, and brain, where they face unique environmental pressures and a wide variety of tissue-resident cells that together create a strong barrier for tumor survival and growth. As a consequence, successful metastatic colonization is critically dependent on reciprocal cross talk between cancer cells and host cells within the target organ, a relationship that shapes the formation of a tumor-supportive microenvironment. Here, we discuss the mechanisms governing organ-specific metastasis in breast cancer, focusing on the intricate interactions between metastatic cells and specific niche cells within a secondary organ, and the remarkable adaptations of both compartments that cooperatively support cancer growth. More broadly, we aim to provide a framework for the microenvironmental prerequisites within each distinct metastatic site for successful breast cancer metastatic seeding and outgrowth.