HER2 staining intensity has prognostic impact on patients with HER2 type invasive breast cancer

Abstract

Background: Human epidermal growth factor receptor 2 (HER2) is a key marker for breast cancer, and HER2‐targeted therapy has improved the prognosis of patients with HER2 overexpressed breast cancer. HER2‐targeted therapies will be recommended for both HER2 IHC 3+ tumors and HER2 IHC 2+ tumors with reflex ISH positivity. However, the prognoses may be different in these two groups of patients. We hypothesized that patients with HER2 IHC 3+ tumor would have better response to anti‐HER2 therapy due to higher HER2 protein expression, and their prognosis would be better than those with HER2 IHC 2+ tumor. This study aimed to evaluate whether the degree of HER2 IHC positivity affected the outcome of early breast cancer. Design: Clinicopathological information of 785 consecutive cases of HER2+ early breast cancer were retrieved from the medical records. The median follow‐up time was 45.5 months. The results of ER, PR and HER2 immunohistochemistry and HER2 ISH were evaluated according to current guidelines. Reflex ISH test using fluorescence in situ hybridization was performed for cases with an equivocal HER2 IHC result (score 2+). Additional HER2 ISH test was performed on 64 randomly selected cases with a positive HER2 IHC result (score 3+) to evaluate the copy number of HER2 gene. The results were correlated with the survival of patients. Results: Hormonal receptor positivity, single anti‐HER2 agent treatment and tumor recurrence occurred more frequently in HER2 IHC 2+ cases than in HER2 IHC 3+ cases. Both HER2 signals and HER2/ CEP17 ratio of the HER2 IHC 3+ group were significantly higher than those of the HER2 IHC 2+ group (p < 0.001). Recurrence‐free survival of cases with HER2 IHC 3+ tumor was significantly better than that of cases with HER2 IHC 2+ tumor (p = 0.018). However, the difference of overall survival between cases with HER2 IHC 3+ tumors and those with score 2+ tumors did not reach statistical significance (p = 0.085). Multivariate analyses revealed that hazard ratios of cases with HER2 IHC 3+ was significant smaller than those with HER2 IHC 2+ in both RFS (p = 0.001) and OS (p = 0.007) with adjustment of age, stage, hormonal receptor status, and anti‐HER2 treatment. Conclusions: The intensity of HER2 IHC provided prognostic information for HER2���positive breast cancer. The prognosis of HER2 IHC 3+ cases was significantly better than that of HER2 IHC 2+ and ISH amplified cases. (Table presented) .