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

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.

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

“…Nevertheless, there is an ongoing debate on whether HER2-low breast cancer is a distinct entity, but there is a lack of data on this subject, particularly in a Chinese population. A recent published study by our institution analyzed the HER2-low breast cancer in the metastatic setting and concluded that HER2 low expression was related to a better OS ( 21 ). In the present study, we focused on early-stage patients, comparing the clinicopathological characteristics and prognosis between HER2-zero and HER2-low breast cancer with a different HR status.…”

Comparison of Management and Outcomes in ERBB2-Low vs ERBB2-Zero Metastatic Breast Cancer in France

“…In the TNBC population, the frequency of ERBB2 -low expression has been estimated from 21.0% of the patients in our study to 35.0% in previous reports. 14 , 15 We did not notice any difference in tumor grade or the number or type of metastases, whereas de novo metastatic disease was also more frequent in the ERBB2 -low group. Recently, Agostinetto et al 13 presented a retrospective analysis of molecular characteristics of 410 patients with primary ERBB2 -low BC, among whom 74 had TNBC.…”

“…All large-scale reports have been based on registry studies that included patients who were treated before the establishment of this new category. Two recently published large studies 15,16 The overall discordance rate from primary tumor to metastasis was 40.9% (1005 tumors).…”

“…A positive impact was also significant in the hormone receptor–positive group (54.9 months vs 48.1 months; P = .01) but not in the hormone receptor–negative subgroup ( P = .72). 15 On the other hand, other studies have failed to demonstrate any impact of ERBB2 -low status in a metastatic setting. 14 , 16 , 26 In early BC, a study 12 enrolling 2310 patients with ERBB2 -zero early BCs from neoadjuvant trials showed that patients with ERBB2 -low BC had a lower pathological complete response to neoadjuvant chemotherapy compared with patients with ERBB2 -zero tumors (29.2% vs 39.0%; P < .001) suggesting lower chemosensitivity.…”

“…Regarding metastatic disease, very few and contradictory data are available. 15 , 16 Considering the new emerging therapies for ERBB2 -low BC, especially in a metastatic setting, a better description of the epidemiology, response to treatment, and outcomes of that population seems important. Our goal was to provide a comprehensive analysis of ERBB2 -low metastatic BC (MBC) management and prognosis compared with ERBB2 -zero MBC in, to our knowledge, the largest cohort to date.…”