P4-08-04: Preoperative Thrombin Pathway Activation Identifies Node Positive Patients in Early Breast Cancer.

Abstract

Abstract Activation of the thrombin pathway (TP) is seen in 50% of cancers and plays a significant role in promoting metastasis. Cancer-induced TP activation is exacerbated by surgery, and this activation may be greater in the presence of metastases. Our aim was to determine if pre-operative plasma d-dimer, a marker of TP activation, correlated with the presence of LN metastases in early breast cancer. We also examined whether surgery-induced TP activation is affected by tumour-associated factors. Methods Plasma d-dimer was measured using automated ELISA pre-operatively and at days 1 and 42 following surgery in 103 prospectively recruited patients undergoing surgery for early breast cancer(87 invasive,13 DCIS). D-dimer values were log-transformed and correlated with LN metastases, tumour size and grade and hormone receptor status using parametric statistical tests. Results Median age was 68 years (range 46–82). Mean tumour size was 14.6 mm (range 7.5-40). Seventy invasive cancer patients had wide local excision(WLE) and sentinel node biopsy(SNB) and 17 had mastectomy(MX) +/− axillary clearance(ANC). Twenty-two patients had positive lymph nodes at primary surgery (MX 8,WLE 14). Of these 3(14%) were ER-ve and 19(86%) were ER+ve. Mean pre-operative d-dimer was higher (p<0.01) in LN positive (704ng/ml, 95% confidence interval, CI, 455–1088) versus LN node negative invasive cancers (443ng/ml, CI 304–627) or DCIS (366ng/ml, CI 284–471). D-dimer was also higher in patients with lymphovascular invasion (612ng/ml, CI 423–886) than in those without (454ng/ml, CI 385–534) and this approached significance (p=0.084). Post-operative d-dimer was higher (p<0.05) after MX compared to WLE at all timepoints. Following WLE + SNB for invasive cancer, post-operative d-dimer rose and was higher at day 1 and day 42 in LN positive vs LN negative and in ER negative versus ER positive cancers (see table). Repeated measures ANOVA analysis showed that the change in d-dimer over time was significantly different between subjects according to LN status (p=0.037) or ER status (p=0.015). Only one patient in the ER negative group had LN metastases. There was no association between pre or postoperative d-dimer and tumour size, tumour grade or PR status. Conclusion Pre-operative TP activation and the thrombotic response to surgery (as measured by d-dimer) is greater in the presence of LN metastases regardless of tumour size. ER negative cancers (7/8 of which were LN negative) also resulted in a greater d-dimer rise, suggesting a difference in the thrombotic response to surgery between different cancer phenotypes. Ongoing work will determine if peri-operative TP activation can act as an independent predictor of node status and cancer recurrence. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-04.