1MO HER2DX assay and survival outcomes: An individual-patient level meta-analysis of 2,031 patients with HER2-positive breast cancer

The 27-gene HER2DX test predicts pathological complete response (pCR) following neoadjuvant trastuzumab-based chemotherapy for HER2-positive (HER2+) breast cancer. Furthermore, HER2DX was associated with survival outcomes across individual studies using different treatment strategies. Here, we combine the existing data to evaluate the prognostic capacity of HER2DX to predict survival outcomes. We conducted an individual-patient level meta-analysis of seven cohorts including 2,031 patients with early-stage HER2+ breast cancer with HER2DX, clinical and efficacy data (SCAN-B n=757, APT n=284, PHERGain n=272, CALGB40601 n=263, ATEMPT n=187, NEOHER n=184, and PAMELA n=84). HER2DX risk score was evaluated i) as continuous score (from 0 to 100) and ii) as a risk group using pre-established cut-offs low [0, 50) and high [50,100). The primary endpoint of the study was event-free survival (EFS). The Kaplan-Meier method was used to estimate survival outcomes and the stratified Cox model was performed to calculate hazard ratios (HRs). The overall median follow-up was 6.4 years, 52.4% of patients were classified into the HER2DX low-risk category and 47.6% as high-risk. In the multivariable analysis, HER2DX risk-score as a continuous variable was statistically associated with EFS after adjustment by study and clinical-pathological variables (HR per 10-units increment= 1.29, 95% CI 1.16-1.42; p<0.001). The 6-years EFS was 93.0% for the HER2DX low-risk and 82.9% and for the HER2DX high-risk (HR=2.25, 95% CI 1.43-3.54; p=0.001). The association remained consistent across all subgroups, regardless of tumor and nodal stage, pCR, and hormone receptor status (Table).Table: 1MOHER2DX risk-score continuous HR, 95%CIHER2DX risk-group HR, 95%CIOverall (n=2,031)1.29 (1.16 – 1.42)2.25 (1.43 – 3.54)Tumor stageT1 (n=1,005)1.19 (1.07 – 1.34)2.59 (1.35 – 4.95)T2-T3-T4 (n=1,026)1.20 (1.10 – 1.30)2.06 (1.32 – 3.23)Nodal stageN0 (n=1,192)1.30 (1.16 – 1.46)2.62 (1.54 – 4.45)N1-N2-N3 (n=576)1.33 (1.06 – 1.65)No events in the low-riskHormone receptor statusPositive (n=1,334)1.24 (1.15 – 1.34)2.73 (1.73 – 4.32)Negative (n=697)1.19 (1.08 – 1.32)2.41 (1.37 – 4.22)Outcomes at surgerypCR (n=341)1.18 (0.97 – 1.43)1.91 (0.75 – 4.87)Residual disease (n=462)(1.09 – 1.33)2.94 (1.66 – 5.18)No neoadjuvant treatment (n=1,228)1.23 (1.13 – 1.34)2.34 (1.39 – 3.94) Open table in a new tab In patients with early-stage HER2+ breast cancer, HER2DX provides prognostic information on long-term outcomes beyond clinical-pathological variables and pCR status.