'And every man that walks through that door will be compared to you forever more.' These lyrics are simple, but they perfectly illustrate one of the stages of divorce: grief, mourning the loss of a relationship you thought would last forever. Full disclosure: I've never been divorced, but I imagine this is a key step in the healing process. It's also probably the hardest, which gives 'Best Friend' even more resonance.
Couple this with the fact that Madonna is notoriously closed off. Any sign of vulnerability from her is novel, so for her to release a song like 'Best Friend'—with lyrics like 'I miss your brain, the way you think, but I don't miss the way you used to drink'—is jarring, to say the least. It shows no one is immune to the pain of divorce, not even the Queen of Pop.