The natural history of breast cancer and the link between local recurrence and distant metastases: implications for therapy

Abstract

This study had two aims:

• 1)

  to assess the tumour size at metastatic dissemination by analyzing the relationship between tumor diameter and incidence of distant metastases during the 25 years after initial treatment,

• 2)

  to investigate the impact of a residual tumor on the probability of distant dissemination.

An analysis of the data registered at the Institut Gustave Roussy in Villejuif was undertaken on about 4000 breast cancer patients treated prior to the use of adjuvant chemotherapy and followed-up for over 15 years.

The data show that the volume at which dissemination occurs in 50% of patients can be estimated in each subset of patients as defined by the size of the tumour, histopathologic grade and number of involved axillary nodes. This V₅₀ varies widely but is inversely correlated with the histologic grade and the number of involved axillary nodes. Moreover, a gradual increase in the grade of the tumours was observed during their growth, confirming the usefulness of early treatment and breast screening.

The analysis of the delay between the initial treatment and clinical emergence of the metastases shows that the excess of distant metastases in patients with local recurrence corresponds to disseminations which are initiated after initial treatment, and therefore originated from the residual tumor. This finding emphasizes the importance of loco-regional treatment.

Whereas during the first 2 years after treatment the incidence of distant metastases was lower in the arm treated by chemotherapy (P=0.32, NS), from the third year on, the reverse was observed and the incidence of metastases was significantly lower in the group treated by post-op RT + poly A – poly U (P<10⁻⁴). At 15 years, the incidence was significantly lower in the group treated by post-op RT + poly A – poly U (42% metastasis-free survival in the RT group and 29% in the CT group p=0.03). This result seems to be due mostly to lower incidence of local recurrence. But even in patients without local recurrence, the incidence of distant metastasis is not greater than that in patients treated by CMF, which might be due to the favourable effect of poly A – poly U. The results of this trial are consistent with those of other recent clinical trials, and emphasize the favourable impact of post-op RT and the paramount importance of local control on the long-term outcome of the disease.