Predictors of response to neoadjuvant treatment and changes to HER2 status in HER2-positive invasive breast cancer

Abstract

Background and purpose: The response of human epidermal growth factor receptor 2 (HER2)-positive invasive breast cancer to HER2 targeted neoadjuvant therapy is significant. However, the response is not uniform, and a proportion of patients respond poorly. This study aimed to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive breast cancer. Methods: The study group included 110 HER2-positive breast cancer patients treated with neoadjuvant therapy and surgery who were diagnosed from 2019 to 2021 in Shenzhen People’s Hospital. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to detect the expression of HER2 in core needle biopsy specimens. Pathological complete response (pCR) and residual cancer burden (RCB) of surgically resected specimens after neoadjuvant therapy were used to assess the therapy response of patients. HER2, estrogen receptor (ER) and progesterone receptor (PR) status were further assessed in the residual invasive carcinoma present after neoadjuvant therapy. Results: One hundred and ten breast cancer patients were divided into IHC diffuse 3+ group (n=81), heterogeneous 3+ group (n=20), IHC 2+ and FISH amplified (2+FISH+) group (n=9). The pCR rate of HER2 diffuse 3+ group was 54.3%, which was significantly higher compared with heterogeneous 3+ group (5.0%) and 2+FISH+ group (11.1%), and the difference was statistically significant (P<0.05). RCB categories were higher in heterogeneous 3+ and 2+FISH+ groups. Multivariate analysis showed that HER2 diffuse 3+ was an independent predictor of pCR. Seven cases (11.9%) became HER2-negative, the majority (85.7%) from heterogeneous 3+ and 2+FISH+ groups. Conclusion: HER2 heterogeneity predicts the neoadjuvant therapy response of HER2-positive breast cancer. Evaluation of the heterogeneity of HER2 IHC in biopsy specimens and repeating HER2, ER and PR testing after neoadjuvant treatment should therefore be considered, which will facilitate further management decisions. The patients with HER2 heterogeneity may potentially benefit from the novel antibody-drug conjugate (ADC).

Keywords

• |human epidermal growth factor receptor 2 heterogeneity|breast cancer|neoadjuvant therapy