Cancers 2010, 2, 305-337; doi:10.3390/cancers2020305 cancers ISSN 2072-6694 www.mdpi.com/journal/cancers Review Surgery Triggers Outgrowth of Latent Distant Disease in Breast Cancer: An Inconvenient Truth? Michael Retsky 1, *, Romano Demicheli 2 , William Hrushesky 3 , Michael Baum 4 and Isaac Gukas 5 1 Harvard School of Public Health, BLDG I, Rm 1311, 665 Huntington, Ave., Boston, MA 02115, USA 2 Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy; E-Mail: Romano.Demicheli@istitutotumori.mi.it 3 University of South Carolina, School of Medicine, Columbia, SC, USA; E-Mail: WilliamHrushesky@gmail.com 4 Royal Free and UCL Medical School, Centre for Clinical Science and Technology, Clerkenwell Building, Archway Campus, Highgate Hill, London, N19 5LW, UK; E-Mail: michael@mbaum.freeserve.co.uk 5 Breast Unit, Department of General Surgery, James Paget University Hospital, Gorleston, Great Yarmouth, UK; E-Mail: igukas@hotmail.com * Author to whom correspondence should be addressed; E-Mail: Michael.Retsky@gmail.com; Tel.: +1-203-675-0017. Received: 9 March 2010; in revised form: 25 March 2010 / Accepted: 26 March 2010 / Published: 30 March 2010 Abstract: We review our work over the past 14 years that began when we were first confronted with bimodal relapse patterns in two breast cancer databases from different countries. These data were unexplainable with the accepted continuous tumor growth paradigm. To explain these data, we proposed that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell phase and the avascular micrometastasis phase. We also suggested that surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. These iatrogenic events are apparently very common in that over half of all metastatic relapses progress in that manner. Assuming this is true, there should be ample and clear evidence in clinical data. We review here the breast cancer paradigm from a variety of historical, clinical, and scientific perspectives and consider how dormancy and surgery-driven escape from dormancy would be observed and what this would mean. Dormancy can be identified in OPEN ACCESS