Abstract
BackgroundPrecise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry (pathological grade). There is a need to replace subjective criteria with objective measurements to improve risk assessment and therapeutic decisions. We assessed the prognostic value of fractal dimension (an objective measure of morphologic complexity) for invasive ductal carcinoma of the breast.MethodsWe applied fractal analysis to pan-cytokeratin stained tissue microarray (TMA) cores derived from 379 patients. Patients were categorized according to low (<1.56, N = 141), intermediate (1.56-1.75, N = 148), and high (>1.75, N = 90) fractal dimension. Cox proportional-hazards regression was used to assess the relationship between disease-specific and overall survival and fractal dimension, tumour size, grade, nodal status, estrogen receptor status, and HER-2/neu status.ResultsPatients with higher fractal score had significantly lower disease-specific 10-year survival (25.0%, 56.4%, and 69.4% for high, intermediate, and low fractal dimension, respectively, p < 0.001). Overall 10-year survival showed a similar association. Fractal dimension, nodal status, and grade were the only significant (P < 0.05) independent predictors for both disease-specific and overall survival. Among all of the prognosticators, the fractal dimension hazard ratio for disease-specific survival, 2.6 (95% confidence interval (CI) = 1.4,4.8; P = 0.002), was second only to the slightly higher hazard ratio of 3.1 (95% CI = 1.9,5.1; P < 0.001) for nodal status. As for overall survival, fractal dimension had the highest hazard ratio, 2.7 (95% CI = 1.6,4.7); P < 0.001). Split-sample cross-validation analysis suggests these results are generalizable.ConclusionExcept for nodal status, morphologic complexity of breast epithelium as measured quantitatively by fractal dimension was more strongly and significantly associated with disease-specific and overall survival than standard prognosticators.
Highlights
Precise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry
Higher fractal dimension was significantly associated with traditional indicators of poor prognosis, including older age, larger tumour sizes, higher tumour grade, and positive lymph node status
Fractal dimension was not associated with either estrogenreceptor status or HER-2/neu status
Summary
Precise criteria for optimal patient selection for adjuvant chemotherapy remain controversial and include subjective components such as tumour morphometry (pathological grade). There is a need to replace subjective criteria with objective measurements to improve risk assessment and therapeutic decisions. The prognostic assessment of breast cancer is based on factors that determine a patient’s relapse risk, and together with predictive factors (e.g., estrogen-receptor status), it is used to make optimal therapeutic decisions regarding adjuvant systemic therapy [1]. Such decisions provide a balance between the potential benefit and associated costs and side effects of treatment [1]. Approximately onethird of node-positive patients are free of recurrence after local-regional therapy [6,7,8]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call