Investigating HER2-Low in Early Breast Cancer: Prognostic Implications and Age-Related Prognostic Stratification

Recent studies about human epidermal growth factor receptor 2 (HER2)-low values have garnered great interest among oncologists. We aimed to investigate whether HER2-low impacts the prognosis of early-stage breast cancer overall and in specific subgroups, explore differences in clinicopathologic markers, and examine the role of age in HER2-low prognostic stratification.

We conducted a retrospective analysis of 6920 HER2-negative breast cancer patients from the First Affiliated Hospital of Wenzhou Medical University (2010-2022). The study focused on the impact of HER2-low status (immunohistochemistry +1 or +2, in situ hybridization not amplified) on overall survival (OS), considering the age at diagnosis.

Generally, HER2-low status correlated with less aggressive cancer indicators. No significant prognostic differences were observed between HER2-low and HER2-0 in the entire cohort, HR-positive, and HR-negative groups. However, in TNBC patients aged ≥ 65, HER2-low correlated with significantly better OS (HR = 0.45, 95% CI 0.24-0.83, p = 0.011), a finding consistent after multivariable adjustment (HR = 0.34, 95% CI 0.14-0.80, p = 0.014). In other subgroups, prognosis did not significantly correlate with HER2 status. The combination of HER2-low status and age plays a key role in prognostic stratification in TNBC. Patients aged ≥ 65 with HER2-0 had considerably poorer prognoses compared to other subgroups.

This extensive retrospective study demonstrates that HER2-low status cannot serve as an independent prognostic factor in the entire cohort, nor in the HR-positive and HR-negative groups individually. However, the combined factors of HER2-low status and age may indicate a potential contribution to the prognostic stratification of TNBC.