From what I understand, it predominantly stays local to the vaginal tissues. Vaginally applied estrogen is not the recommended route for the prevention of bone loss whereas oral and transdermal applications are. Vaginal estrogen is prescribed to prevent the vaginal tissues from atrophy, create a healthier vaginal environment and thus prevent (hopefully) UTIs which are more common as we age. It is considered safe for all ages, even prescribes for 90+ year old women. I don't know about those with a history of breast cancer but I would bet Dr Bluming addresses this in his updated book, Estrogen Matters. Perhaps the doses are much lower in a vaginal cream application and with repeated application, the tissues themselves get saturated locally (that is why with a transdermal patch, they always recommend regularly rotating the site to not saturate the tissues).