Aims Human epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT. Methods 527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.0 and HER2 copy numbers >= 6.0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17 >= 2.0 and HER2 copy numbers >= 4.0 and <6.0; group C: HER2/CEP17 >= 2.0 and HER2 copy numbers >= 6.0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups. Results According to HER2 FISH results, 12 patients (2.3%, 12/527) were in group A, 40 (7.6%, 40/527) were in group B and 475 (90.1%, 475/527) were in group C. The pCR rate was the lowest in group B (5.0%), while the pCR rates in group A and group C were 33.3% and 44.4%, respectively (p ((group A vs. B)) =0.021, p ((group C vs. B)) < 0.001). Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p ((group C vs. B)) < 0.001, p ((group C vs. B)) = 0.025). Conclusions Patients with HER2/CEP17 >= 2.0 and HER2 copy numbers >= 4.0 and <6.0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns.
