The impact of HER2 discordance on patient prognosis following anti-HER2 neoadjuvant therapy for HER2-positive breast cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) discordance between biopsy and residual disease (RD) is common in HER2-positive breast cancer (BC) after anti-HER2 neoadjuvant therapy (NAT). This study investigated the impact of HER2 discordance on oncological outcomes. METHODS: Consecutive HER2-positive BC patients who received anti-HER2 NAT were identified from a prospective database. HER2 status was evaluated for both biopsy specimens and RD before and after NAT. The prognostic implications of HER2 discordance were assessed. RESULTS: A total of 700 HER2-positive BC patients were enrolled, 267 (38.1%) of whom achieved pathological complete response (pCR) after NAT. For patients with RD after NAT, the HER2 status of RD was HER2 (3+) in 209 (29.9%), HER2 (2+) in 144 (20.6%), and HER2 (1+ or 0) in 80 (11.4%) patients. A total of 217 patients exhibited HER2 changes after NAT, including 183 (26.1%) cases with loss and 34 (4.9%) with gain of HER2 positivity. There was no significant difference (P>0.05) in 5-year invasive disease-free survival (IDFS) between patients with different HER2 statuses of RD after NAT (87.3%, 84.2% and 80.9% for no change, loss and gain of HER2 positivity, respectively). Multivariate analysis indicated that cN+ (HR 3.946, 95% CI 1.535-10.148; P = 0.004), Miller-Payne grade of 3-4 (HR 0.499, 95% CI 0.278-0.933; P = 0.040) and pre-NAT HER2 (3+) (HR 0.479, 95% CI 0.251-0.915; P = 0.026) were independent prognostic factors for IDFS in patients without pCR after anti-HER2 NAT. CONCLUSION: HER2 discordance after anti-HER2 NAT was observed in a substantial proportion of HER2-positive BC patients. However, neither the change of HER2 nor the specific HER2 status after NAT was associated with the prognosis. Moreover, pre-NAT HER2 status was a robust prognostic factor in HER2-positive BC patients who received anti-HER2 NAT.