Work

Comparison of Stromal Tumor-Infiltrating Lymphocyte (sTIL) Levels and Clinicopathological Features in Neoadjuvant-Naive HER2-Low and HER2-Negative Primary Breast Cancers

Year: 2026

Type: article

Abstract: Background and Objective: The clinical success of novel antibody-drug conjugates has led to the identification of a new subgroup within traditionally HER2-negative breast cancers, termed ‘HER2-low.’ The aim of this study was to investigate the clinicopathological differences between HER2-low and HER2-negative groups in neoadjuvant-naive primary breast cancer patients, with a specific focus on stromal tumor-infiltrating lymphocyte (sTIL) density. Materials and Methods: The study included 731 neoadjuvant-naive invasive breast cancer patients. Tumors were classified as HER2-negative (IHC 0) and HER2-low (IHC 1+ or 2+/ISH-negative). sTIL levels were evaluated following the International TILs Working Group guidelines. Results: The HER2-low group (38.7%) demonstrated significantly higher histological grade (p = 0.033) and higher sTIL density (p = 0.006) compared to the HER2-negative group. A stepwise increase in sTIL rates was observed parallel to the HER2 immunohistochemical score (0 → 1+ → 2+) (p = 0.015). The HER2-low/hormone receptor (HR)-negative subgroup exhibited the highest sTIL density (median 35%). No statistically significant difference in overall or disease-free survival was found between the groups. Conclusions: HER2-low breast cancers were associated with a more immunogenic tumor microenvironment compared to HER2-negative tumors. This robust immune infiltration may offset the higher histological grade observed in the HER2-low cohort, potentially explaining the comparable survival outcomes. These findings provide a biological rationale for exploring the synergy between novel antibody–drug conjugates and immune checkpoint inhibitors, particularly in the highly immunogenic HER2-low/HR-negative subgroup.

Source: Medicina

DOI: 10.3390/medicina62050826

Authors: Mümin Emiroğlu, Esra Canan Kelten Talu, Cem Karaali, Olçun Ümit Ünal, Mihriban Erdoğan

Institutions: Sağlık Bilimleri Üniversitesi, Izmir Tepecik Eğitim ve Araştırma Hastanesi, İzmir Şehir Hastanesi

Language: English

Topic: Breast Cancer Treatment Studies

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,654