14P Assessing the predictive value of HER2DX pCR-score for pathologic complete response (pCR) in early-stage HER2-positive (HER2+) breast cancer (BC) under real-world conditions

The effectiveness of the HER2DX pCR-score in predicting pCR to anti-HER2 neoadjuvant chemotherapy (NACT) in patients (pts) with HER2+ BC in real-world clinical setting has not been thoroughly evaluated. This study aims to assess the performance of the HER2DX pCR-score in a clinical environment at a single institution. We analyzed standardized HER2DX pCR-scores from pts with stage I-III HER2+ BC receiving trastuzumab-based CT at the Hospital Clinic of Barcelona between Nov/21 - Jan/24. This cohort was not previously included in HER2DX validation datasets. The primary goal was to explore the association between HER2DX pCR-score groups and pCR, considering hormone receptor (HR) status, Ki67, TILs, grade, HER2 IHC (3+ vs. 2+), and the type of CT (single taxane vs. multi-agent). Logistic regression methods were employed for statistical analysis. We included 86 pts with a median age of 51.9 years. Median TILs were 15.0%, 62.8% were HR+, 48.0% had grade 3, 20.9%, 61.6% and 17.4% were diagnosed with stage I, II and III, respectively, and 67.4% were treated with multi-agent CT. The overall pCR rate was 64.0% (95% CI 53.9.-74.0). The distribution across HER2DX pCR-high, -medium, and -low groups was 46.5%, 20.9%, and 32.6%, respectively, and the distribution ofHER2DX risk high and low was 58.1% and 41.9%, respectively. Univariable analysis demonstrated a significant association between HER2DX pCR score and pCR (high vs. low, odds ratio = 5.4, p = 0.002). In the multivariable model, HER2DX pCR-score remained associated with pCR after adjustment by clinico-pathological variables and type of CT (high vs low, OR = 7.4, 95% CI 1.37-40.25; p = 0.020). The pCR rates in the HER2DX pCR-low and pCR-high groups were 35.7% and 75.0%, respectively. The selection of multi-agent versus single-agent CT was strongly associated with the HER2DX risk group. The HER2DX pCR-score is significantly associated with pCR in pts with early-stage HER2+ BC undergoing anti-HER2-based NACT in a real-world setting. A low HER2DX pCR-score is consistently correlated with a reduced likelihood of achieving pCR, independently of the use of multiagent CT and clinico-pathological factors.