A quantitative model for lung colonization by benign mammary cells in breast cancer

Metastasis is a complex and multifaceted process that can vary greatly between patients and cancer types. There are many models describing different pathways leading to ectopic colonization, however most share the assumption that all metastatic lesions are initiated by cancerous cells that have been ejected from (and are therefore clonal offspring of) the primary tumor. Nevertheless, intertumoral heterogeneity among metastatic lesions with respect to each other and the primary paints a more complicated picture of clonal relationships and heritage, one which is not always compatible with such linear models. Here we examine an alternative pathway to lung colonization in breast cancer. Recent findings show that in mice healthy mammary stem cells may form proliferating colonies in the lungs when injected in the tail vein, and that a growing tumor in the mammary gland may induce dissemination of neighboring mammary epithelial cells to the lungs. If an oncogenic mutation occurs in such a colony the resulting lesion would not share the same mutational history as the primary tumor and would therefore contribute to heterogeneity and possible treatment failure.