"Breslin will have surgery within a couple of weeks," Orgeron said. "He will be out an extensive period of time, but he could get back later."
With only four regular-season matchups left, the hope would be that Breslin could return for a bowl game for the Trojans (6-3, 3-2 Pac-12).
The 6-foot-2, 250-pound Breslin already has missed several games this season due to injuries to his hip and ankle (Hawaii, Arizona, Utah and Oregon State). In the five games he played, he had 15 tackles to go with 4.5 sacks and eight tackles for a loss.
Breslin led the Trojans in sacks in 2012 with 13 and was named to the All-Pac-12 Second Team.
"In 27 years of coaching, Breslin is one of my favorite players," Orgeron said. "He is totally dedicated to football and has a unique sense of humor."
The loss of Breslin will be felt primarily in the pass rush for the Trojans, although versatile junior J.R. Tavai has filled in well for him in the past, including 10 tackles (3.5 for a loss) against Arizona. But Tavai might be needed elsewhere for USC on Saturday at California as defensive end Leonard Williams has missed the past two practices with a shoulder injury and is questionable to play.
Tavai was the top reserve to Williams in fall camp and would be his likely replacement at defensive end, with Jabari Ruffin as the probable replacement for Breslin in that scenario.
Orgeron also said there is nothing set along the offensive line as the coaches continue to evaluate the status of injured right tackle Kevin Graf. With Graf sidelined for the Oregon State game due to an ankle injury, the Trojans moved Max Tuerk to right tackle and inserted John Martinez, the former right guard, at left guard.
Orgeron called Graf probable for the Cal game.
"We like the continuity we had on the line last week from the previous game," Orgeron said. "The key is, how much can Kevin go? We don't know that yet."
Josh Shaw was also limited in action Wednesday at cornerback, with Torin Harris taking the first-unit reps across from Kevon Seymour. Orgeron said Shaw was just "a little banged up" so the team was giving him some rest while allowing Harris to get some valuable time.