Comparative analysis of the clinicopathological features and prognostic implications of invasive breast carcinoma of nonspecial type exhibiting HER2-low and HER2-zero expressions.

Purpose: This retrospectively study aimed to investigate the clinicopathological features, treatments, prognostic differences, and influencing factors between invasive breast carcinoma of nonspecial type (IBC-NST) with low and zero HER2 expressions.

Methods: Clinical data of patients with IBC-NST exhibiting low and zero HER2 expression were obtained from the Shanghai Jiao Tong University Breast Cancer Database spanning July 2009 to December 2019. The Kaplan-Meier method, log-rank test and Cox regression analyses were performed.

Results: Of the 2071 patients with IBC-NST, 1618 (78.1%) had low HER2 expression and 453 (21.9%) had zero HER2 expression. A higher proportion of patients aged below 40 years, with Ki67 >20%, and with tumor grade III were observed in the HER2-zero group. Higher percentages of estrogen receptor-positive, progesterone receptor-positive, hormone receptor (HR)-positive, and receipt of endocrine therapy were observed in the HER2-low group. The breast cancer-free interval (BCFI) and overall survival (OS) were similar between the groups. In the HR-positive subgroup, no significant differences were observed in the clinical pathological characteristics, treatment types, BCFI, and OS. In the HR-negative subgroup, higher proportions of patients aged over 40 years and patients in the postmenopausal stage were observed in the HER2-low group. Multivariate analysis revealed that the lymph node stage (N2-N3) was an independent risk factor for BCFI and OS regardless of the HER2 status. Meanwhile, HER2-low was an independent risk factor for BCFI in the HR-negative subgroup (hazard ratio, 1.781, 95% confidence interval, 1.061-2.989, P = 0.029).

Conclusion: The clinical biological characteristics of HER2-low IBC-NST could be influenced by the HR status. The clinicopathological features and prognosis of HER2-low and HER2-zero IBC-NST were comparable at the same HR status.