Wallabies rake Polota-Nau fractured his arm in the 32-15 defeat at Canberra Stadium on Friday night, while new recruit Hegarty has suffered a suspected anterior cruciate ligament injury.
Wallabies centre Horne also suffered a knee injury and the Waratahs could yet lose replacement hooker Tolu Latu to suspension for their next game against New Zealand's champion Otago Highlanders at home in two weeks.
Latu was cited for punching Brumbies centre Matt Toomua in the second half.
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"It was a tough night," coach Daryl Gibson said after his side's first defeat in two matches this season.
"But injuries are all part of the season and that's why you have a squad."
(Reporting by Ian Ransom; Editing by Nick Mulvenney)
