**2.6 Problems in Ki-67 assessment**

	- a. Spatial heterogeneity: the number of cells needed to be counted for consistent results might be much lower in tumors with low proliferation and high in tumors with high proliferation
	- b. Temporal heterogeneity: This is commonly observed as a result of therapy. Several studies have shown that the short-term reduction of Ki-67 after 2 weeks of therapy is predictive of the outcome of endocrine therapy [5, 6, 21]
