Impact of c-MYC protein expression on outcome of patients with early-stage HER2⁺ breast cancer treated with adjuvant trastuzumab NCCTG (Alliance) N9831

Purpose: This study investigated the association between tumorMYCprotein expression and disease-free survival (DFS) of patients randomized to receive chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the N9831 (Alliance) adjuvant HER2⁺ trastuzumab breast cancer trial. Experimental Design: This analysis included 1,736 patients randomized to Arms A, B, and C on N9831. Nuclear MYC protein expression was determined in tissue microarray sections containing three biopsies per patient or whole tissue sections using standard immunohistochemistry (clone 9E10). A tumor was considered positive for MYC protein overexpression (MYC⁺) if the nuclear 3+ staining percentage was more than 30%. Results: Five hundred and seventy-four (33%) tumors were MYC⁺. MYC⁺ was associated with hormone receptor positivity (χ², P = 0.006), tumors 2 cm or more (χ², P = 0.02), and a higher rate of nodal positivity (χ², P < 0.001).HRs for DFS (median follow-up: 6.1 years) for Arm Cversus Awere 0.52 (P=0.006) and 0.65 (P =0.006) for patients with MYC⁺ and MYC ^- tumors, respectively (P_interaction=0.40). For Arm B versus A, HRs for patients with MYC⁺ and MYC^- tumors were 0.79 (P = 0.21) and 0.74 (P = 0.04), respectively (P_interaction=0.71) . For Arm C versus B, HRs for patients with MYC⁺ and MYC^- tumors were 0.56 (P=0.02) and 0.89 (P = 0.49), respectively (Pinteraction = 0.17). Conclusions: Our data do not support an impact of tumorMYCprotein expression on differential benefit from adjuvant trastuzumab.