Comparison of the prognostic value of mitotic frequency and mitotic activity index in breast cancer

Previous studies have shown that the Mitotic Activity Index (MAI), defined as the number of mitotic figures in 10 consecutive well-defined high power fields, is a strong and reproducible prognosticator in breast cancer. However, cellularity of tumours may vary. The Mitotic Frequency (MF), defined as the number of mitoses per a certain number of tumour nuclei, corrects for cellularity and therefore may have higher prognostic value than the MAI. The present study was undertaken to test this hypothesis by comparing the prognostic value of MAI and MF. In 189 primary invasive breast cancer patients, the MAI was assessed by counting the total number of mitoses in 10 consecutive fields in the most cellular area in the periphery of the tumour. In the same fields the MF was determined by calculating the fraction of mitoses in 2000 nuclei. The time needed for the respective determinations was registered. Univariate survival analysis (Kaplan-Meier curves, Mantel-Cox test) showed that both counting methods were strong prognosticators (P < 0.0001), but the MF was a slightly stronger prognostic factor than the MAI as reflected by the Mantel-Cox value (20.9 versus 18.1). MF and MAI showed, however, no clear differences in sensitivity, specificity, efficiency, and predictive value of positive and negative test results. In multivariate analysis, the MAI had slightly more additional prognostic value to lymph node status and tumour size. Assessment of MF took 30-45 min on average, 3 times longer than MAI assessments. In conclusion, MF and the MAI showed no marked difference with regard to prognostic value. Considering the ease and speed of MAT assessment, it remains a useful prognosticator for daily practice in management of breast cancer patients.