Breast cancer as a disease of self-seeding: concept, evidence, and clinical implications


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Larry Norton
Memorial Sloan-Kettering Cancer Center, New York, USA

Abstract

<p>The conventional view of cancer is that cells from a primary tumour mutate toward metastatic potential as they grow and evolve, sending off metastatic cells as they develop, which then colonize distant sites: a one-way process.</p><p>There is now a body of evidence that metastasis is a more complex system, involving sets of genes that determine site-specific seeding, with the primary tumour itself one of those sites. That is, cancer cells may enter the circulation from the primary tumour, and then re-seed that tumour and also the organ of origin contiguous to and a small distance from the primary location. These seeds increase tumour growth by promoting angiogenesis and the infiltration of marrow-derived supporting stroma. The genes responsible for such self-seeding are similar but not identical to those causing distant metastases.</p><p>This concept could explain why irradiation to the involved breast is necessary to prevent distant metastases after breast-conserving surgery to clear margins, why anaplasia is so closely linked to vascularity and metastatic potential, why molecular profiling predicts metastatic behaviour, why patients with primary breast cancer so rarely have distant metastases at the time of first diagnosis, and why antimitotic therapy is in general not curative in the stage IV setting. Furthermore, the self-seeding concept suggests new targets for anticancer therapy, including the seeding process itself.</p><br>