Distribution, dynamic evolution, and clinical outcomes of patients with advanced breast cancer according to HER2 expression

Abstract

Background: Novel antibody‒drug conjugates (ADC) have shown great efficacy in HER2-low advanced breast cancer. However, the clinical features of HER2-low disease still need to be clarified. The current study aims to evaluate the distribution and dynamic change in HER2 expression in patients with disease recurrence and the clinical outcome of those patients. Methods: Patients with pathologically diagnosed relapsed breast cancer between 2009 and 2018 were included. Samples were considered HER2-zero when the immunohistochemistry (IHC) score was 0, HER2-low when the IHC score was 1 + or 2 + with negative fluorescence in situ hybridization (FISH) results, and HER2-positive when the IHC score was 3 + or the FISH results were positive. Breast cancer-specific survival (BCSS) was compared among the three HER2 groups. Changes in HER2 status were also evaluated. Results: A total of 247 patients were included. Among recurrent tumors, 53 (21.5%) were HER2-zero, 127 (51.4%) were HER2-low, and 67 (27.1%) were HER2-positive. The HER2-low subtype represented 68.1% of the HR-positive breast cancer group and 31.3% of the HR-negative group (P < 0.001). This three-group classification of HER2 status was prognostic in advanced breast cancer (P = 0.0011), with HER2-positive patients having the best clinical outcome after disease recurrence (P = 0.024), while only marginal survival advantages were observed in HER2-low patients versus HER2-zero patients (P = 0.051). In the subgroup analysis, the survival difference was observed only in patients with HR-negative recurrent tumors (P = 0.0006) or with distant metastasis (P = 0.0037). The overall discordance rate of HER2 status between primary and recurrent tumors was 38.1%, with 25 (49.0%) primary HER2-zero patients and 19 (26.8%) HER2-positive patients shifting to HER2-low at recurrence. Conclusion: Nearly half of the advanced breast cancer patients had HER2-low disease, which indicates a poorer prognosis than HER2-positive disease and marginally better outcomes than HER2-zero disease. During disease progression, one-fifth of tumors convert to HER2-low entities, and the corresponding patients may benefit from ADC treatment.