Comparative Evaluation of Clinical and Pathological Characteristics of Breast Cancers with Low HER2 Receptor and Negative HER2 Receptor

Nazarian, Niyosha; Eslami, Bita; Kani, Fatemeh Elham; Alipour, Sadaf; Mirmalek, Seyed Abbas; Omranipour, R

Comparative Evaluation of Clinical and Pathological Characteristics of Breast Cancers with Low HER2 Receptor and Negative HER2 Receptor

Document Type : Original Article

Authors

Niyosha Nazarian ¹

Bita Eslami ²

Fatemeh Elham kani

Sadaf Alipour ³

Seyed Abbas Mirmalek ⁴

R Omranipour ⁵

¹ 1General Physician, Faculty of Medicine, Islamic Azad University, Tehran Medical Branch

² Assistant Professor, Breast Diseases Research Center, Cancer Research Institute, Tehran University of Medical Sciences

³ Professor, Department of Cancer Surgery, Faculty of Medicine, Tehran University of Medical Sciences, Arash General Women's Hospital

⁴ Assistant Professor, Department of General Surgery, Islamic Azad University, Tehran Medical Branch, Bu Ali Hospital

⁵ Professor, Department of Cancer Surgery, Cancer Institute, Faculty of Medicine, Tehran University of Medical Sciences, Imam Khomeini Hospital

Abstract

Background and Objective: Breast cancers that overexpress the HER2 receptor tend to exhibit more aggressive behavior compared to other breast cancer subtypes. As a result, HER2 status plays a critical role in prognosis and treatment planning. Recently, increasing attention has been given to differences among HER2-Negative cases, which include three subgroups: 0, 1+, and 2+ (with Negative results on FISH or CISH tests), collectively referred to as “HER2-low.” Emerging evidence suggests that these subgroups may differ biologically. This study aimed to investigate the clinical and pathological characteristics of these three HER2-Negative subgroups, with a particular focus on tumor features.
Materials & Methods: This cross-sectional analytical study included data from 3,745 patients with HER2-Negative breast cancer. Categorical variables were analyzed using the Chi-Square test, while continuous variables were assessed based on normality with appropriate test.
Results: The mean age of the patients was 50.96 ± 11.37 years. Comparative analysis showed that patients in the HER2-intermediate ISH-Negative group were significantly younger than those in the other two groups (p = 0.030). Tumor size was smaller, and the mean Ki-67 index was higher in this group compared to the others (p < 0.001). Additionally, grade 3 tumors (22.1%), positive surgical margins (9%), and metastasis (11.1%) were more common in the HER2-intermediate ISH-Negative group. This group also had the highest recurrence (26.1%) and mortality rates (24.7%). Conversely, the HER2-zero group had the largest average tumor size (28.74 ± 19.59 mm), the highest lymph node involvement (53.2%), and the greatest incidence of lymphovascular invasion (58.6%). The HER2-low 1+ group appeared to be the least aggressive, showing the lowest rates of grade 3 tumors (13.7%), positive margins (4.3%), and recurrence (11.5%). Regarding treatment, the majority of HER2-zero and HER2-low 1+ patients received adjuvant chemotherapy (62.3% and 51.3%, respectively), while neoadjuvant chemotherapy was more commonly administered to patients in the HER2-intermediate ISH-Negative group (52%).
Conclusion: Based on the findings of this study, patients in the HER2-intermediate ISH-Negative group exhibited more aggressive tumor characteristics and poorer outcomes compared to the other HER2-Negative subgroups. In contrast, the HER2-low 1+ group demonstrated the most favorable prognosis. These results suggest that patients with HER2-intermediate ISH-Negative status may benefit from closer monitoring and more frequent follow-up to improve clinical outcomes.

Keywords

Breast Cancer

HER-2 receptor

HER2-low

HER2-borderline

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