In Real Life, Low-Level HER2 Expression May Be Associated With Better Outcome in HER2-Negative Breast Cancer: A Study of the National Cancer Center, China.

Yiqun Li,Zijing Wang,Binghe Xu,Jiayu Wang,Fei Ma,Shanshan Chen,Yang Luo,Ying Fan,Nilupai Abudureheiyimu,Qing Li,Qiao Li,Hongnan Mo,Peng Yuan,Pin Zhang,Yimeng Chen,Shaoyan Lin,Ruigang Cai,Xiuwen Guan

doi:10.3389/fonc.2021.774577

Abstract

BackgroundTo characterize the clinical and pathological features and survival of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer in China.MethodsThe China National Cancer Center database was used to identify 1,433 metastatic breast cancer patients with HER2-negative disease diagnosed between 2005 and 2015. Clinicopathological features, survival, and prognosis information were extracted. Overall survival (OS) was estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95% CI).ResultsThere were 618 (43.1%) and 815 (56.9%) HER2-low and HER2-zero tumors out of 1,433 tumors, respectively. The proportion of hormone receptor (HR)-positive tumors was significantly higher in HER2-low tumors than in those with HER2-zero tumors (77.8% vs. 69.2%, p < 0.001). Patients with HER2-low tumors survived significantly longer than those with HER2-zero tumors in the overall population (48.5 months vs. 43.0 months, p = 0.004) and HR-positive subgroup (54.9 months vs. 48.1 months, p = 0.011), but not in the HR-negative subgroup (29.5 months vs. 29.9 months, p = 0.718). Multivariate regression analysis revealed that HER2-low tumors were independently associated with increased OS in HER2-negative population (HR: 0.85, 95% CI: 0.73–0.98, p = 0.026).ConclusionOur findings demonstrate that HER2-low tumors could be identified as a more distinct clinical entity from HER2-zero tumors, especially for the HR-positive subgroup. A more complex molecular landscape of HER2-low breast cancer might exist, and more precise diagnostic algorithms for HER2 testing could be investigated, thus offering new therapeutic targets for breast cancer treatment.

Highlights

Human epidermal growth factor receptor 2 (HER2) is a prototype oncogene that belongs to the HER (EGFR,ErbB) family [1]
According to the most updated guidelines established by the College of American Pathologists (CAP), estrogen receptor (ER)/progesterone receptor (PgR) positivity were defined as ≥10% positive tumor cells with nuclear staining by IHC and ≥1% after April 2010. (ii) HER2-negative breast cancer
We identified 2,202 patients with metastatic breast cancer (MBC) diagnosed between January 2005 and December 2015 at the National Cancer Center, China

Summary

Introduction

Human epidermal growth factor receptor 2 (HER2) is a prototype oncogene that belongs to the HER (EGFR,ErbB) family [1]. Among the 80%–90% HER2-negative breast cancers, a low to moderate expression of HER2 (IHC1+ or IHC2+/ISH-negative) still exists and such tumors are identified as HER2-low tumors [8]. Tumors classified as HER2-negative are not targetable with conventional anti-HER2 therapies [9]. Two HER2-targeted antibody–drug conjugates (ADCs), trastuzumab deruxtecan (T-DXd) [10] and trastuzumab duocarmazine (SYD985) [11], have shown promising antitumor activity in patients with HER2-low breast cancer, offering novel therapeutic options for HER2-low tumors and shifting the attention of physicians toward this particular subset of patients [12, 13]. To characterize the clinical and pathological features and survival of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer in China

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