van der Breggen put a jerk in a heavy uphill with 41 km left to drive and no one else in the field managed to catch up.
She bumped when Dutch teammate Annemiek van Vleuten got on the bike and led the remaining small group of five cyclists.
van Vleuten made a spectacular start.
In the overall lead of the Giro Rosa (ladies' Giro d'Italia) last week, she crashed and went on a fracture in the wrist.
A metal washer was operated on to stabilize the injury and the reigning champion was able to start, tightly bandaged and in pain, during the year, which she led for a while.
Will end after the Olympics next year
The whole group was gathered when the bell rang for the last lap (out of five) on the Imola track.
The chasing group was then 1.44 after the fleeing van der Breggen when 28.8 kilometers remained to go.
It was a lap of honor for van der Breggen, who piled up titles in the final part of his career.
30-year-old van der Breggen has decided to retire after the Tokyo Olympics, which have been postponed to next summer.
After her active career, however, she plans to continue in cycling.
Then she will become a coach in her stable Boels-Dolmans.