Prognostic values of clinical and molecular features in HER2 low-breast cancer with hormonal receptor overexpression: features of HER2-low breast cancer.

Background: Human epidermal growth factor receptor 2 (HER2) low breast cancer was considered as a distinct subtype different from HER2-zero breast cancer. Our study aimed to investigate the prognostic values of clinicopathological features and recurrence score (RS) in HER2-low and HER2-zero hormone receptor (HR)-positive breast cancer patients.

Methods: A total of 2099 HR + primary female breast cancer patients diagnosed between Jan 2009 and Jan 2019 were collected. Tumors with immunohistochemistry 1 + /2 + and negative in situ hybridization results were defined as HER2-low. We compared the clinical and genetical features of HER2-low (n = 1732) and HER2-zero (n = 367) breast cancer and their prognostic values.

Results: Estrogen receptor (ER) high expression (> 90%) was more common in HER2-low breast cancer than HER2-zero breast cancer (78.2% vs 58.6%, p < 0.01). Five-year disease-free survival (DFS) was similar between HER2-zero and HER2-low subgroups (92.3% vs 93.3%, p = 0.83). The predictive value of RS was only significant in HER2-zero patients (p = 0.03). The proliferation-related genes performed well in predicting DFS in HER2-zero patients, but not in HER2-low patients (p for interaction < 0.01). The higher HER2 module score was correlated with worse DFS only in HER2-low patients (p = 0.04).

Conclusion: We observed similar survival outcomes between HER2-low and HER2-zero HR + patients. HER2-low patients had a higher proportion of ER high expressed tumors than HER2-zero patients did. RS and its proliferation module might be less clinically meaningful to HER2-low patients.