The link between local recurrence and distant metastases in human breast cancer

Purpose: To distinguish between two possible explanations for the increased incidence of distant metastases observed in patients with locoregional recurrences (LR). Either LR is the signature of tumor aggressiveness, and avoiding recurrences (i.e., by radiotherapy) is of little value. The alternative is that LR is a nidus for metastatic dissemination. Methods and Materials: Four thousand patients consecutively treated in the same institution from 1954 to 1975 were studied. None of them had received adjuvant chemotherapy, Tumor characteristics, local recurrence, and distant metastases had been prospectively registered. Duration of metastatic growth and probability of metastatic dissemination were estimated in the subsets of patients. Results: The proportion of metastasis-free patients was reduced by about 80% in all subsets of patients with LR, In patients without LR, the monthly rate of distant metastases incidence decreases continuously with time after initial treatment, Conversely, in patients with local recurrence, this rate increases during the first year after initial treatment and the metastases in excess appear slightly later than in patients without local recurrence. Using a mathematical model, it can be shown that, in patients with local recurrence, nearly all of the metastases in excess had been initiated after initial treatment. The data also suggest that each year a small proportion of grade I residual tumors progresses toward a more malignant histologic type. Conclusions: Our results are not consistent with the hypothesis that a greater tumor aggressiveness in patients with LR could explain the excess of metastases, This conclusion is supported by the analysis of the delays between metastases' emergence, and death, which shows that tumors with or without LR have similar biological characteristics. (C) 1998 Elsevier Science Inc.