Molecular biology of breast cancer metastasis: Clinical implications of experimental studies on metastatic inefficiency

Recent technological advances have led to an increasing ability to detect isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes or bone marrow. However, the clinical significance of these cells is unclear. Should they be considered as evidence of metastasis, necessitating aggressive treatment, or are they in some cases unrelated to clinical outcome? Quantitative experimental studies on the basic biology of metastatic inefficiency are providing clues that may help in understanding the significance of these cells. This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients

Metastatic dormancy imposed by the primary tumor: does it exist in humans?

Contains fulltext : 69245.pdf (publisher's version ) (Closed access)BACKGROUND: In cancer patients, occult micrometastases may become apparent shortly after removal of the primary tumor. Animal experiments have shown that metastatic dormancy is maintained by apoptosis, and that primary tumor removal induces a flare-up of angiogenesis, leading to metastatic outgrowth. This phenomenon has led to the hypothesis that the primary tumor generates certain factors that inhibit angiogenesis at distant sites. It is still unknown whether such a phenomenon is operative in human cancer as well. Should it occur, it might have important therapeutic consequences. MATERIALS AND METHODS: Evidence for such a mechanism may be obtained from studies that analyze a series of tissue samples of metastases, taken before or after surgical removal of the primary lesion. RESULTS: Data from our laboratory on colorectal cancer have shown that, in the absence of the primary tumor, vascular density in the metastases is increased as well as their metabolic activity, as measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Mitotic activity is increased mildly, while levels of apoptosis are collapsed. CONCLUSION: These data indicate that a mechanism of primary-tumor-induced inhibition of angiogenesis exists, maintaining metastatic dormancy. We now suggest that this mechanism may be exploited to avoid the use of exogenous, potentially harmful angiogenesis inhibitors such as bevacizumab in a neoadjuvant setting. Treatment of patients with the primary tumor still in situ could thus be restricted to chemotherapy, since the synergistic effect of an angiogenesis inhibitor would be generated by the primary tumor itself. In the present paper the clinical relevance and possible consequences of our findings and suggestions are discussed