All patients

12 24 36 48

72 84 96 108 120

Survival time (months)

Figure 3.5 Survival curves for invasive breast cancer patients grouped according to the apoptotic index (AI) and the mitotic activity index (MAI).244

studied, and increased proliferation correlates strongly with poor prognosis, irrespective of the methodology used. However, from the different ways to assess proliferation, mitosis counting has most convincingly been proved to provide reproducible and independent prognostic value in invasive breast cancer. The MAI is therefore used in clinical practice in several European countries. The Ki67/MIB1 labeling index is a promising alternative, but needs further methodological fine-tuning. In general, it must be admitted that little attention has yet been paid to the value of these proliferation markers in predicting response to therapy. The apoptotic index is a new, promising prognostic factor. Further larger and prospective clinical studies are needed to establish its true clinical value.

Although much knowledge has been gained about genes implicated in the complex regulation processes of proliferation and apoptosis, analysis of individual genes is as yet clinically unsatisfactory, and analysis of the functional end-results of these complex processes - rate of proliferation and apoptosis - is far more important. This may, however, change when sophisticated statistical models become available to interpret complex microarray expression patterns.

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