Effect of IGF1R protein expression on benefit to adjuvant trastuzumab in early-stage HER2+ breast cancer in NCCTG N9831 trial.

10503 Background: Preclinical evidence suggests that increased IGF1R (insulin-like growth factor receptor) signaling interferes with trastuzumab action, suggesting a possible mechanism of resistance. Thus, we evaluated IGF1R prevalence, relationship with demographic data, and association with disease-free survival (DFS) of patients (pts) randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the prospective phase III HER2+ adjuvant N9831 trial. Methods: The % of cells with IGF1R staining at 0 (none), 1+ (weak), 2+ (moderate), and 3+ (strong) intensity was determined in TMA sections containing 3 cores per block (N=1210) or whole tissue sections (WS) (N=536) using IHC (Cell Signaling 1:200). A tumor was considered positive (IGF1R+) if any core or WS had ≥1+ membrane staining in >0% invasive tumor cells. Median follow-up was 6.1 yrs. Other cutpoints of positivity, including ≥2+ and 3+ membrane staining in >0% invasive tumor cells were also examin...