Editors' ChoiceBreast Cancer Micrometastases

Micrometastases + Math = Model of Breast Cancer Dormancy

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Science Translational Medicine  09 Jun 2010:
Vol. 2, Issue 35, pp. 35ec92
DOI: 10.1126/scitranslmed.3001332

Breast cancer survivors can never really relax, because their malignancies can recur decades after a patient is diagnosed. Indeed, breast cancer displays a striking ability to remain dormant for years after surgery with metastases at distant locations. Tumor cells likely are released from the main tumor bulk early in the course of disease, seed lymph nodes and organs, and reside in a quiescent state as “micrometastases” until reactivated by growth signals and a release from immune surveillance. In a recent article by Willis et al., the authors used mathematical modeling to identify factors that promote breast cancer dormancy, with a special emphasis on micrometastases.

Using approximate Bayesian computation, they evaluated the impact on breast cancer dormancy—or growth restriction—of (i) the average number of micrometastases after resection; (ii) the frequency of seeding within pro-metastatic environments; and (iii) the effects of metastasis rate, disappearance rate, and growth rate of micrometastatic cells. A key assumption used in their calculations is that, as previously reported, steady-state numbers of circulating tumor cells in breast cancer may indirectly correlate with dormancy. The results of the current study suggest that a surprisingly low number of micrometastases are required for tumor relapse. Specifically, the number of dormant micrometastases needed to ultimately cause relapse ranges from one to three, with most patients harboring only one “dangerous” micrometastasis. Furthermore, most micrometastases are likely to be >0.4 mm in diameter and to have the capacity to escape growth restriction with a half-life of >12 years. The time frame for the development of relapse, however, may vary based on the initial size, vascular status, and growth-restriction half-life of the micrometastasis, parameters to be further analyzed in future studies.

L. Willis et al., Breast cancer dormancy can be maintained by small numbers of micrometastases. Cancer Res. 70, 4310–4317 (2010). [Full Text]

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