Abstract
Circulating tumour cells (CTCs) are a marker of poor prognosis and are associated with increased risk of venous thromboembolism in metastatic breast cancer. We aimed to correlate presence of CTCs and markers of hyper-coagulability (D-dimer, fibrinogen and thrombin-antithrombin [TAT]) with survival in metastatic breast cancer. In a prospective study, enumeration of CTCs (CellSearch) and D-dimer, fibrinogen and TAT (ELISA) were measured at a single timepoint in 50 MBC (median age 59, range 36-82) patients undergoing active treatment. Survival data was determined at a median follow-up of 366days (range 58-986). To date, 25 patients have died (median survival 566days, range 135-978). CTCs (>1/7.5ml) were identified in 13 patients (range 2-31) and were associated with increased markers of hypercoagulability [D-dimer: median 1814 (IQR 2700) vs 755 (IQR 735) ng/ml, p=0.004; fibrinogen: median 4.2 (IQR 1.9) vs 3.2 (1.3) g/l, p=0.05; TAT: median 6.2(IQR 6.3) vs 4.7 (5.2) ng/ml, p=0.1]. CTCs were associated with visceral compared to just bony metastases (p=0.03) and their presence was associated with a trend for reduced survival (295days (CI: 0-652) vs 737days (CI: 186-1288), p=0.1). There was no correlation between CTCs /markers of hypercoagulability and age, oestrogen receptor, progesterone receptor or Her2 status. D-dimer, fibrinogen and TAT all inversely correlated with survival and were all significantly higher in patients dying within 1year (D-dimer: 1098 (IQR 1122) vs 723 (IQR 735) ng/ml, p=0.03; fibrinogen: 4.4 (1.1) vs 3.2 (0.8) g/l, p=0.004; TAT: 8.1 (6.3) vs 4.7(3.1) ng/ml, p=0.03 [analysis excludes patients with <1year follow-up, n=13]). D-dimer >1,500ng/ml was associated with significantly reduced survival (295days [CI: 0-615] vs 836days [404-1267], p=0.05). On Cox regression, D-dimer, but not fibrinogen or TAT was associated with an increased risk of death (HR 1.3 per 1,000ng/ml D-dimer, p=0.07). The correlation between CTCs, hypercoagulability and reduced survival in metastatic breast cancer suggests a possible role for the coagulation system in supporting tumour cell metastasis and is therefore a potential therapeutic target.
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