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Plasma D-Dimer Levels in Operable Breast Cancer Patients Correlate With Clinical Stage and Axillary Lymph Node Status

From the Divisions of Medical and Radiation Oncology, Duke University Comprehensive Cancer Center, Durham, NC.

Address reprint requests to Charles Greenberg, MD, Department of Medicine and Pathology, Duke University Medical Center, Durham, NC 27710; email green032{at}mc.duke.edu

PURPOSE: To investigate the relationship between preoperative plasma D-dimer levels and extent of tumor involvement in operable breast cancer patients.

PATIENTS AND METHODS: A total of 140 preoperative plasma specimens were obtained from women scheduled to undergo diagnostic breast biopsies. Ninety-five patients in the initial group went on to undergo axillary lymph node dissection. Of the 140 patients from whom plasma samples were obtained, 102 were subsequently diagnosed with invasive breast carcinoma, nine were subsequently diagnosed with ductal carcinoma-in-situ, and 20 were subsequently diagnosed with benign breast disease. Plasma D-dimer levels were quantitated using a commercially available immunoassay kit (DIMERTEST; American Diagnostica, Greenwich, CT). The relationships between plasma D-dimer and other prognostic variables (tumor size, estrogen receptor, progesterone receptor, nuclear grade, histologic grade, lymphovascular invasion, and clinical stage grouping) were then examined using univariate and multivariate linear and logistic regression analyses.

RESULTS: Median plasma D-dimer levels were significantly higher in patients with invasive carcinoma than those patients with either benign breast disease or carcinoma-in-situ (P = .0001). A significant relationship existed between the presence of elevated D-dimer (> 100 ng/mL) and involved axillary lymph nodes (² test; P = .001). Elevated D-dimer levels predicted positive lymph node involvement in both univariate regression (P = .0035) and multivariate linear regression (P = .012) models. In addition, elevated D-dimer levels predicted the presence of lymphovascular invasion in univariate logistic regression (P = .0025) and multivariate logistic regression analysis (P = .0053). Quantitative D-dimer levels were highly correlated with clinical stage grouping (analysis of variance test; P = .002).

CONCLUSION: Plasma D-dimer levels were markers of lymphovascular invasion, clinical stage, and lymph node involvement in operable breast cancer. This correlation suggests that detectable fibrin degradation, as measured by plasma D-dimer, is a clinically important marker for lymphovascular invasion and early tumor metastasis in operable breast cancer.

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