Normal updates mess with nothing special.
If there is a
NEW toolbar item,
YOU must choose to add, as Calibre will not mess up your
thoughtfully 
customized toolbars.
Standard Icons may change. CUSTOM icons (those in the configuration folder path), stay
There will be advisories (they are few) here at MR and change notes, when the OLD way differs.
The last biggie was 'T' (
Tweakbook now
Unpack) Became the shortcut for the e-book editor.