Prognostic significance of HER2 loss after HER2-targeted neoadjuvant treatment in patients with HER2-positive locally advanced breast cancer

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25–30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.