Prognostic indicators of metastatic bone disease in human breast cancer

The time to detection of metastatic bone disease (MBD) by radiographic examination was studied in 221 patients with advanced breast cancer. None of the patients had bone metastases by radiography or bone marrow carcinosis, evaluated by bilateral iliac crest biopsy. The period of follow-up after first recurrence was 46 months. Fifty-five patients (25%) had MBD; 89 patients died without MBD. The cumulated rate of MBD was 14% and 27% after 1 and 2 years, respectively. The actuarial time to MBD was associated significantly with the presence of positive regional lymph nodes at primary diagnosis, the occurrence of metastases in the mediastinum, and the presence of visceral metastases. Moreover, a positive bone scintigraphic scan at the time of first recurrence and abnormal biochemical analyses from serum also were associated significantly with a shortened time to MBD. Micrometastases in the bone marrow, as detected by monoclonal antibodies against epithelial markers (epithelial membrane antigen and cytokeratin), were present in 18% of the patients. The presence of such tumor cells was not associated with development of radiologic MBD. Cox analyses revealed that the result of bone scintigraphic scanning and the presence of visceral metastases were the most important and independent predictors of the time of MBD. Four distinct prognostic groups were identified based on the status of these two variables. The recognition of these prognostic groups has several implications for clinical and therapeutic management of patients with recurrent breast cancer.