Clinicopathological Significance of HER2 Expression Redefined by the HER2-low Concept in Ductal Carcinoma In Situ

The introduction of the HER2-low concept has redefined the biological spectrum of breast cancer. However, the clinicopathological and prognostic significance of HER2 expression in ductal carcinoma in situ (DCIS) remains unclear. This study aimed to reassess HER2 expression in DCIS using the HER2-low classification.

A total of 221 patients who underwent surgery and were pathologically diagnosed with DCIS at Osaka Metropolitan University hospital between June 2007 and December 2023 were retrospectively analyzed. HER2 expression was assessed using immunohistochemistry (IHC) and classified as HER2-0, HER2-low (IHC 1-2+), or HER2-high (IHC 3+). Clinicopathological features were compared among groups, and disease-free survival (DFS) and recurrence-free interval (RFI) were evaluated using Kaplan-Meier and Cox regression analyses.

HER2-0, HER2-low, and HER2-high were observed in 96 (43.4%), 80 (36.2%), and 45 (20.4%) patients, respectively. HER2 expression correlated significantly with estrogen receptor (p=0.011), progesterone receptor (p<0.001), comedonecrosis (p=0.030), calcification (p=0.019), and nuclear grade (p=0.006). Although no significant differences were found among the three groups, the HER2-0 subgroup tended to show longer RFI compared with HER2-positive cases (p=0.051). Multivariate analysis identified tumor size as an independent prognostic factor for DFS (hazard ratio=34.47, p=0.004).

HER2 expression redefined by the HER2-low concept reflects the biological diversity of DCIS. Evaluation of HER2 status as a continuous spectrum may aid in risk stratification and contribute to understanding early HER2-driven tumor evolution.