Dynamic HER2-low status among patients with triple negative breast cancer (TNBC) and the impact of repeat biopsies

Trastuzumab deruxtecan (T-DXd) is approved for HER2-low (HER2 immunohistochemistry (IHC)1+ or 2+ with non-amplified in situ hybridization (ISH)), but not HER2-0 (IHC 0) metastatic breast cancer. The impact of repeat biopsies (Bxs) in identifying new potential candidates with triple negative breast cancer (TNBC) for T-DXd treatment remains unknown. 512 consecutive patients with TNBC at diagnosis were included in the study cohort. Bxs were categorized as core, surgical, or metastatic based on the timing and method of biopsy (Bx) acquisition, and the total number of Bxs was determined for each patient. Additionally, matched biopsies were identified, and the rate of discordance in HER2 status was calculated. The proportion of patients with at least one HER2-low result increased as the number of successive Bxs increased [59%, 73%, 83%, 83%, and 100% when 1 (196 patients), 2 (231 patients), 3 (48 patients), 4 (29 patients), and ≥ 5 (8 patients) Bxs were obtained, respectively]. Among patients without a prior HER2-low result, approximately one-third demonstrated HER2-low status with each additional successive Bx. HER2 status exhibited variability between matched Bxs, with observed discordance rates of 26%, 44%, and 33% between matched core-surgical, early-metastatic, and two metastatic matched Bxs, respectively. Our findings indicate that HER2 status can vary between different Bxs taken during the disease course of patients with TNBC with the highest discordance rate observed between the primary and metastatic Bxs. For patients with metastastic HER2-0 TNBC, repeat Bxs can increase the chance of obtaining a HER2-low result, thereby offering patients a promising therapeutic option.