Solved. Ended up being an incorrect configuration selected in the debug menu. I had mistakenly switched it to a release configuration that could not load the symbols for the document. Switched it to a debug configuration and the breakpoints hit just fine now.
To add on to what Abacus mentioned below, it could also be a web.config transform that is messing with your build. In our case, we have Release configurations that remove the debug
attribute from the web.config's compilation section. Below is a screenshot of an example and Visual Studio's dropdown list of build configurations.
NOTE: Also make sure your Platform is correct along with the configuration. In my case, Dev.Debug|Mixed Platforms
does not correctly build the solution but Dev.Debug|Any CPU
will.