If we use an aspx page with a Caching Profile, the server caches images that are loaded with the aspx page. So if ten clients load the same image through the aspx page (same url), for one client the image is gotten out of the db, for the nine others it is cached.
When we use a HttpHandler, this doesn't happen. The image is always fetched from the database. We have tried all different settings without any success. (we have checked this link and have not been able to cache on server side).
I can't answer based on experience of using the caching profile, so I'm not sure if this helps.
Under the covers, ASP.NET WebForms are driven by HttpHandlers - written by MS (as you'd expect). When you write you own Http Handler you don't automatically get all the functionality that the System.Web.UI.PageHandlerFactory handler has (the one that by default looks after .aspx pages/requests) - you have to bring it in (or develop it) yourself.
Maybe this is the problem you have - maybe the Caching Profile capabilities are being leveraged by the aspx pages because the System.Web.UI.PageHandlerFactory is already "integrated" with it out of the box, where-as when you write your own they just aren't there (by default) - and hence the they don't work.