Clinicopathological Characteristics and Prognosis of HER2-Low Early-Stage Breast Cancer: A Single-Institution Experience

Abstract

BackgroundHuman epidermal growth factor 2 (HER2)-low breast cancer, which is defined as HER2 1+ or 2+ in immunohistochemistry without gene amplification, accounts for a considerable part of all breast cancers. However, it remains controversial whether HER2-low breast cancer is a distinct entity. Our aim was to compare the clinicopathological features and survival outcomes between HER2-zero and HER2-low early breast cancer.MethodsThe study was a retrospective analysis that enrolled 1,039 patients with available HER2 expression data in a single institute from 2013 to 2014, of whom 262 HER2-positive patients were excluded from the subsequent analysis. The remaining patients were divided into HER2-zero and HER2-low groups. Each group was further categorized into a hormone receptor (HR)-positive and an HR-negative subgroup. Clinicopathological characteristics were collected and compared between HER2-zero and HER2-low groups. The primary endpoint was disease-free survival (DFS) and overall survival (OS), which were analyzed using the Kaplan–Meier method with log-rank test, landmark analysis, and Cox proportional hazards model.ResultsA total of 777 non-HER2-positive patients were included in this analysis, of whom 126, 552, 53, and 46 patients were HR-positive/HER2-zero, HR-positive/HER2-low, HR-negative/HER2-zero, and HR-negative/HER2-low, respectively. No significant difference in DFS and OS was detected between the HER2-zero group and the HER2-low group when paired by HR status. Landmark analysis with a time point set at 5 years indicated that HR-positive/HER2-low patients had a better DFS compared with HR-positive/HER2-zero patients after 5 years (p = 0.0047). HER2-low status was an independent prognostic factor for DFS after 5 years [hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.13–0.75, p = 0.01].ConclusionThe clinicopathological characteristics and prognosis of HER2-zero and HER2-low breast cancer were similar regardless of HR status. Patients with HR-positive/HER2-low tumors tended to have a better DFS than their HR-positive/HER2-zero counterparts after 5 years.

Bioinformatics combined with clinical data to analyze clinical characteristics and prognosis in patients with HER2 low expression breast cancer

“…The results of this study are consistent with numerous reports at from China and internationally (28)(29)(30). However, when performing the prognostic analysis, the different HER2 expression intensity of the 345 BC patients in the TCGA cohort was not significantly different from the DFS, which is consistent with the DFS results of our clinical samples, and is also consistent with the findings of other centers in (30)(31)(32). However, in the group with HER2 low expression (P=0.018); in subgroup analysis, the rate with HER2 low expression was significantly lower than in the HER2 zero expression group (P=0.020).…”

Comparison of clinicopathological characteristics and response to neoadjuvant chemotherapy between HER2-low and HER2-zero breast cancer

“…Survival differences between HER2-low and HER2-zero BC varied across studies. Single-center studies such as Xu HC et al [ 32 ] and Zhang GC et al [ 30 ] detected no significant difference in DFS and OS between the two groups, and Rosso et al [ 33 ] reported longer OS in HER2-low tumors compared with HER2-zero. Multicenter studies [ 28 , 29 ] about early HER2-negative breast cancer from Asia demonstrated better outcomes in HER2-low tumors than HER2-zero tumors.…”

Lentiviral vector–based xenograft tumors as candidate reference materials for detection of HER2-low breast cancer

“…It has been demonstrated that the HER2-low patients with IHC0/1+/2+ and FISH negative exhibited different biological and clinical prognostic characteristics from those HER2-positive patients. Novel HER2-directed ADCs have showed efficacy in treating HER2-low patients with IHC scores of 1+ or 2+ and with FISH negative ( 9 ).…”

“…Recently, antibody-drug conjugates (ADCs) have been applied to the ongoing clinical trials of HER2-low BC (2)(3)(4)(5)(6)(7). On the basis of the latest guidelines of the American Society of Clinical Oncology (ASCO)/American College of Pathologists (CAP) for the HER2 detection method and scoring system (8), the HER2-low BC was defined as HER2 immunohistochemistry (IHC) 1+/2+ and fluorescence in situ hybridization (FISH) negative (9,10). It has been shown that nearly 50% of patients with HER2-negative BC were actually classified as HER2-low, allowing them to benefit from the new anti-HER2 therapy (4).…”