Measurement of pharmacokinetic parameters in histologically graded invasive breast tumours using dynamic...

Dynamic contrast-enhanced MRI (DCE-MRI) has demonstrated high sensitivity for detection of breast cancer. Analysis of correlation between quantitative DCE-MRI findings and prognostic factors (such as histological tumour grade) is important for defining the role of this technique in the diagnosis of breast cancer as well as the monitoring of neoadjuvant therapies. This paper presents a practical clinical application of a quantitative pharmacokinetic model to study histologically confirmed and graded invasive human breast tumours. The hypothesis is that, given a documented difference in capillary permeability between benign and malignant breast tumours, a relationship between permeability-related DCE-MRI parameters and tumour aggressiveness persists within invasive breast carcinomas. In addition, it was hypothesized that pharmacokinetic parameters may demonstrate stronger correlation with prognostic factors than the more conventional black-box techniques, so a comparison was undertaken. Significant correlations were found between pharmacokinetic and black-box parameters in 59 invasive breast carcinomas. However, statistically significant variation with tumour grade was demonstrated in only two permeability-related pharmacokinetic parameters: k(ep) (p<0.05) and K(trans) (p<0.05), using one-way analysis of variance. Parameters k(ep) and K(trans) were significantly higher in Grade 3 tumours than in low-grade tumours. None of the measured DCE-MRI parameters varied significantly between Grade 1 and Grade 2 tumours. Measurement of k(ep) and K(trans) might therefore be used to monitor the effectiveness of neoadjuvant treatment of high-grade invasive breast carcinomas, but is unlikely to demonstrate remission in low-grade tumours.