Incidence and kinetics of distant metastases in patients with operable breast cancer

The purpose of this paper is to evaluate the incidence and kinetics of distant metastases in operable breast cancer and to relate these estimates to various tumor and patient characteristics. The records of 309 consecutive patients with operable breast cancer in stage T1-4N0-1M0 were reviewed, and the incidence of distant metastases (DM) and death due to DM were evaluated. 195 patients had positive axillary nodes with the following distribution of the number of nodes: 45% had 1-2 node, 16% had 3-4 nodes, 14% and 25% had 5-7 and more nodes, respectively. All patients were treated with radical mastectomy with axillary nodes dissection (the only treatment in 39% of cases). In 198 cases radical mastectomy was combined with radiotherapy and/or chemotherapy given pre- or postoperatively. Hormonal treatment was given in 27% of cases. Minimum follow-up was 10 years. Distant metastases were found in 150 cases (49%) and in 78 cases (25%) they developed early, during the first 18 months follow-up. Average rate of DM in N0 cases was 25%. Number of involved nodes and extracapsular invasion were found significant and independent prognostic factors. High risk (50%) of DM and death due to DM correlate with age < 40 y, premenopausal status, tumor stage > or = T3, more than 2 axillary nodes and/or extracapsular invasion. The linearity of the curves for freedom from DM and for freedom from death due to the DM suggest uniform distribution of progression rates with a median value for halving time for freedom from early DM of about 8 months, and of about 40 months for freedom from the DM occurring later than 18 months, being for whole group an average of 20 months. High incidence of DM is a significant cause of poor long-term survival. Early appearance (< 18 month follow-up) of about half of the DM suggests that they are already present as subclinical micrometastases at the time of initial loco-regional treatment. The time of appearance of distant metastases is consistent with a wide range of metastatic cell burdens among patients. Systemic therapy, at least for selected group of patients, might decrease the incidence of DM and improve long-term results.