Predictive value of bone marrow accumulation of Tc-99m tetrofosmin for subsequent development of distant metastases in breast cancer

Abstract

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Objectives: Approximately one third of lymph node-negative breast cancer patients relapse with distant metastases due to early tumor cell dissemination. Detection of occult metastases in bone marrow may have a substantial clinical impact on the prognosis and adjuvant therapy. We evaluated the predictive value of bone marrow accumulation of Tc-99m tetrofosmin for distant metastases in comparison with tumor size, axillary lymph node (Node) and estrogen receptor (ER).

Methods: Bone marrow scans with Tc-99m tetrofosmin were performed in 64 patients with breast cancer who had no clinical evidence of distant metastases. Thirty-two patients had scans within 3 months before operation or within one month after operation. Accumulation in the femoral marrow was classified into four patterns; no detectable, lower, equivalent and higher compared with soft tissue accumulation. From previous results of 188 control patients, equivalent or higher accumulation pattern was interpreted as abnor mal. Thirty-five patients with abnormal accumulation (marrow-positive group) and 29 patients without abnormal accumulation (marrow-negative group) were enrolled in the follow-up study. The mean length of observation after scans was 30.0 months in marrow-positive group, and 29.2 months in marrow-negative group.

Results: There were no significant correlations between bone marrow status and tumor size, Node and ER. Follow-up studies showed significantly higher incidence of subsequent distant metastases (bone and /or visceral metastases) in marrow-positive group compared with marrow-negative group (23/35 (66%) > 4/29 (14%), p<0.001). Node and ER were also significant prognostic factors for distant metastases (19/33 (58%) in Node-positive > 8/31(26%) in Node-negative, p<0.01 and 17/27 (63%) in ER-negative > 8/33 (24%) in ER-positive, p<0.005), but tumor size was not significant prognostic factor (21/42 (50%) in size>2 cm vs 6/22 (27%) in size<=2 cm, NS). Multivariate analysis showed that Cox proportional hazard ratio for distant metastases was 2.25 (p=0.187) in tumor size, 2.36 (p=0.043) in Node, 3.60 (p=0.003) in ER and 5.63 (p=0.001) in bone marrow. Kaplan-Meier analysis for distant metastases-free survival demonstrated significantly poorer prognosis in marrow-positive group than marrow-negative group (p<0.0001).

Conclusions: Bone marrow accumulation of Tc-99m tetrofosmin indicates systemic tumor dissemination and can be an important and independent prognostic factor for predicting high risk for subsequent development of distant metastases in breast cancer.