Based on the evaluation of PIK3CA mutations in 504 tumor samples from patients with HER2 in the neoadjuvant studies, including GeparQuattro, GeparQuinto, and GeparSixto, the pCR rate was 11.3% for PIK3CA mutations and 27.5% for wild-type PIK3CA (OR, 0.34; 95% CI, 0.15–0.78; p = 0.01) among 291 patients with luminal/HER2 tumors, whereas the rate was 30.4% for PIK3CA mutations and 40.1% for wild-type PIK3CA (OR, 0.65; 95% CI, 0.32–1.32; p = 0.2) among 213 patients with non-luminal/HER2 tumors. The gene discussed is ERBB2; the disease is neoplasm.