Different criteria for HER2 positivity by IHC can be applied in post-chemotherapy specimens in determining HER2 as a prognosticator in locally advanced breast cancer

Purpose: We evaluated the clinical significance of HER2 in post-chemotherapy specimens after surgery in locally advanced breast cancer (LABC). Methods: Thirty-four patients with LABC were treated with neoadjuvant chemotherapy, surgery, adjuvant chemotherapy, and radiotherapy. The HER2 status was determined using both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in the paraffin-embedded surgical specimens after neoadjuvant chemotherapy. Results: The positive rate of HER2 was 41.2% and 32.4% by IHC and FISH, respectively. As the gene copy number of HER2 detected by FISH increased, the staining intensity by IHC increased with positive correlation (adjusted r ² = 0.743; P < 0.001). According to the cutoff values of IHC score 2+ and 3+ as the positivity criteria, the concordance rates of IHC and FISH were 91.2% (31/34) and 88.2% (30/34), respectively. With the positivity criteria of IHC score ≥2+, the locoregional recurrence-free survival was better in the HER2-negative patients (P = 0.04). Trends were also found for the prolonged distant recurrence-free, disease-free, and overall survivals in the HER2-negative patients by IHC (2+). Trends for poor clinical response (P = 0.06) and more axillary nodes involvement (P = 0.08) were noted in the HER2-positive group by IHC (2+). In post-chemotherapy specimens, the positive HER2 status by IHC staining score ≥ 2+ predicted higher recurrence in LABC. Conclusion: This suggests that different criteria for the HER2 positivity by IHC can be applied in post-chemotherapy specimens compared with that from pre-chemotherapy biopsies.