Background and objectives: Human epidermal receptor 2 (HER2)-low breast cancer, characterised by specific immunohistochemistry (IHC) scores (+1 or +2) or negative fluorescence in-situ hybridiszation (FISH), has unique biological traits, therapeutic outcomes and prognosis. Recent studies highlight the effectiveness of Trastuzumab-Deruxtecan (T-Dxd) for HER2-low patients. This study seeks to deepen understanding of HER2 negative and low patients for tailored treatment by determining the 3-year disease-free survival (DFS) rates and prognostic variables of different subsets of HER2 negative (HER2 0) and HER2-low breast cancer patients (HER2 +1, HER2 +2 and HER2 FISH negative).
Methodology: We analysed the records of 138 patients with non-metastatic breast cancer, exhibiting HER2 IHC 0, +1 or +2/FISH negative. Data on 3-year DFS in months, age, stage (early stage versus locally advanced) and menopausal status were collected. Kaplan–Meier survival curves were used to plot 3-year DFS, while Cox Proportional Analysis assessed the prognostic significance of age and menopausal status in the HER2-low population.
Results: Three-year DFS for HER2 0 was 84.4%, HER2 +1 was 81.8% and HER2 +2/FISH negative was 52.9%, displaying statistically significant differences (p = 0.00012). Subgroup analyses revealed consistently worse DFS for HER2 +2/FISH negative patients in both early and advanced stages (p = 0.0042, 0.0057). Cox proportional analysis showed a recurrence hazard ratio of 4.0–4.5 for HER2 +2/FISH negative patients. Among prognostic factors, post-menopausal status correlated with a decreased risk of recurrence (HR 0.4387), signifying a 56.13% lower recurrence risk compared to pre-menopausal patients (p = 0.00723). On the other hand, patient age was not correlated with a reduced risk of recurrence (HR 0.97; p = 0.0544).
Conclusion: This study reveals a worse 3-year DFS in HER2 +2/FISH negative patients across both early and advanced disease stages. The findings highlight the prognostic importance of HER2-low status and may guide future therapeutic strategies, including the use of targeted therapies like T-Dxd in non-metastatic patients.
