How to apply Sandwich Testing When no. of layers are more than 3

I was studying sandwich testing. And I found a question asked in many lectures I downloaded. How would you select a target layer, when no of layers is greater than 3?

I have searched a lot for the answer. But couldn't find any satisfactory answer. The only thing i found out is to use heuristic approach. I don't know what it is and how to use it. And secondly, in the figure below, In modified sandwich testing. It test (A,B), (A,C) together but not (B,E) and (B,F). Why?