Abstract P3-10-17: The Fractal Analysis of Tumor Histology Is an Independent Prognostic Factor in Breast Cancer Patients

Abstract

Abstract Background: Despite the usefulness of standard clinical prognosticators for breast cancer patients, recommendations for systemic adjuvant therapy are not entirely straightforward. Hence, there is a need for a more accurate independent prognosticator that provides additional information to improve risk assessment and associated therapeutic decisions. Methods: We used fractal dimension analysis to quantitatively assess the morphologic complexity of breast epithelium. To investigate the relationship between fractal dimension and patient survival we applied fractal analysis to pan-cytokeratin stained tissue microarray (TMA) cores derived from a series of 408 patients with over 10 years follow up, and analyzed three TMA cores for each patient. A data-oriented approach was used to stratify patients according to low (<1.56), intermediate (1.56-1.75), and high (>1.75) fractal dimension. Univariate statistical analyses were performed to show the relationship between outcome and fractal dimension, tumour size, tumour grade, lymph node status, estrogen receptor status, and HER-2/neu status. Multivariate analysis was performed to assess the relative effect of these prognosticators on disease-specific and overall survival. Results: Patients with higher fractal score had significantly lower disease-specific 10-year survival (69.4%, 56.4%, and 25.0%, for low, intermediate, and high fractal dimension, respectively, P<0.001). Overall 10-year survival showed a similar association with fractal dimension. Cox regression analysis showed fractal dimension, lymph node status, and grade to be the only significant (P<0.05) independent predictors for both disease-specific and overall survival. Fractal dimension had the highest hazard ratio for overall survival 2.7(95% confidence interval (CI)=1.6-4.7); P<0.001), and the second highest for disease-specific survival 2.6(95% CI=1.4-4.8; P=0.002) versus 3.1(95% CI=1.9-5.1; P<0.001) for lymph node status. Discussion: Except for lymph node status, morphologic complexity of breast epithelium as measured by fractal dimension is more strongly and significantly associated with disease-specific and overall survival than standard clinical prognosticators. Furthermore, it is independent of standard prognosticators, and unlike tumour grade, it provides prognostic information that can be objectively assessed from TMA cores. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-17.