Evolution of HER2 expression after neoadjuvant therapy in locally advanced gastric cancer

HER2 is a crucial biomarker in gastric cancer, influencing both treatment strategies and patient prognosis. A multicenter retrospective study was conducted, including 398 patients with locally advanced gastric cancer who received neoadjuvant treatment (NAT) followed by gastrectomy between 2018 and 2023 at three medical centers in China. Alterations in HER2 expression after NAT were detected in more than 40% of patients, with a higher rate of decreased expression (26.0%) compared to increased expression (17.3%). Multivariate analysis indicated that HER2 status at diagnosis significantly influenced HER2 expression alteration. Patients with HER2 IHC 2+ tumors before NAT demonstrated an increased tendency for HER2 expression alterations after NAT. Decreased HER2 expression was associated with improved recurrence-free survival and overall survival. PD-1/PD-L1 inhibitors and trastuzumab both increased pCR rates, but neither significantly impacted the rate of HER2 expression alterations among non-pCR patients. Reassessing HER2 status after NAT is essential for guiding HER2-targeted therapies.