DHM will work on the charity's flagship campaign, 'Fashion Targets Breast Cancer', which stars supermodel Sophie Dahl.
The long-running campaign, which has previously featured Jade Jagger, Claudia Schiffer and Helena Christensen in press, poster and cinema ads, has raised more than £8m for the charity over the past 11 years.
Fiona Hazell, director of marketing and communications at Breakthrough, said: "We've been looking for a start-up agency that would provide us with the energy and creativity the campaign deserves, and Dye Holloway Murray fit the bill perfectly."
Jorian Murray, DHM's managing partner, said: "We were immediately struck by the Breakthrough team's infectious enthusiasm and hugely impressed with their track record of making extraordinary things happen. We are privileged to be asked to help with such a well-known campaign. "
Breakthrough's media planning and buying duties, handled by Vizeum, are unaffected by the appointment. The charity will also continue to work with outdoor specialist agency Posterscope.