The genesis of overt metastases in breast cancer is based on the idea that tumor cells that dissociate from the primary cancer get access to circulation either directly into blood vessels or after transit in lymphatic channels. Thus, detection of such cells in patients with newly diagnosed solid tumors has been an appealing strategy to provide evidence for future metastases.
In the past, several models have been constructed to explain the presence of individual tumor cells in secondary organs and their influence on the subsequent course of the disease. Currently, according to the most recent transcriptome and genome analyses, circulating tumor cells (CTC) in the bloodstream and those already disseminated to secondary organs [disseminated tumor cells (DTC)] are viewed as rare and much earlier indicators of tumor cell spread, than generally assumed from the typical year-long course of cancerous diseases, such as breast cancer. Despite the observation that the numerous genetic alterations found so far in such cells are rarely identical or even similar, first, the long interval between dissemination and clinical manifest metastases; secondly, the frequently observed relative resistance of some cells to chemotherapy and; thirdly, their significant effect on disease progression despite their low abundance in secondary organs, nourish the idea that some of these cells might be progenitor cells with self-renewing properties that give rise to most of the tumor mass that is dealt with clinically.
Beyond the discussion of such models and opinions, the actual presence of tumor cells outside the primary tumor and in organs relevant for subsequent metastasis formation, such as bone and bone marrow, would serve three purposes that could be clinically useful:
1. as an unambiguous evidence for an early occult spread of tumor cells,
2. as a relevant risk factor for subsequent metastasis and, thus, a poor prognosis,
3. as a marker for monitoring treatment susceptibility.
Finally, and perhaps, as importantly in the long run, genotyping and phenotyping of these cells should provide detailed insight into the metastatic process and permit direct exploration of targeted treatment strategies.
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