Tumor characteristics and survival rate of HER2-low breast cancer patients: a retrospective cohort study

HER2 is an important prognostic marker in breast cancer (BC) patients, which also plays a crucial role in their therapeutic plan. Consequently, a great desire is to thoroughly assess the patients based on their HER2 status. In the current study, we aimed to evaluate HER2-low breast cancer as a new subtype in the standard classification of BC patients and review its characteristics and survival rate in a tertiary center in Iran. We retrospectively evaluated disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics of BC patients referred to the Cancer Research Center in Tehran, Iran from 1991 to 2022. Patients’ clinical characteristics, including HER2 status, which is classified as HER2-low, HER2-positive, or HER2-negative, were obtained from prospectively maintained registries. Among the total 3582 recruited patients, 60.2%, 13.6%, and 26.2% were HER2-negative, HER2-low, and HER2-positive, respectively. HER2-positive patients showed a significantly higher Hazard Ratio (HR) for DFS (HR 1.44, 95% CI 1.01–2.05) and OS (HR 2.05, 95% CI 1.31–3.20), compared to HER2-low. Moreover, HER2-low and HER2-negative were found to show the same proportion of high-grade tumors (28 and 28.4%), while 40% of the HER2-positive tumors were high-grade. Accordingly, HER2-low patients had a lower metastasis risk than the others (P-value = 0.01). The Ki67 percentage was significantly lower in the HER2-low group compared to the HER2-positive (P-value < 0.001). HER2-low, a new subtype of HER2-status classification with distinct biological and clinicopathological traits, represented the highest survival rate and less invasive characteristics. This difference was statistically significant when compared to HER2-positive, but not when compared to HER2-negative. Research registration unique identifying number: NCT05754047.