Driving at 70mph on cruise. Started going downhill and transmission started downshifting on its own all the way to second gear. stepped on brake and op returned. No recurrence of problem on rest of 220 mile trip. Possible cause?

Well, the first honest thought is: the transmission fluid should be serviced every 30,000 miles. 30, 60, 90, 120. I would frown upon a "flush" as this transmission is a 6R80 6 speed automatic and has a thermostat on the valve body which makes it difficult to flush fluid unless the fluid is hot. All that said, downshifting unexpectedly does not sound like an internal hydraulic concern, but rather a shit management concern from sensor data and inputs. Basically, a diagnostic tool should be employed to see if there are any trouble codes present that show problems with the transmission that may have occurred and been noticed by the processor. And, if not, the shift solenoids and commands should be monitored to see if everything is working as it should. The vehicle speed sensor data should also be monitored to ensure it is providing accurate data. Beyond that, getting the problem to happen again while driving with a diagnostic tool actively hooked up and monitoring performance is the only other thing to be done. Good luck.