Clinicopathological features and prognosis of patients with HER2-low breast cancer

Low human epidermal growth factor receptor 2 (HER2) expression is an emerging concept in breast cancer that is defined as immunohistochemistry (IHC) 1 + or IHC 2 + and negative in situ hybridization (ISH) but has been poorly investigated. The aim of our study was to determine the frequency of low HER2 expression among HER2-negative breast cancers and compare the clinicopathological features and prognosis of HER2-low patients with those of HER2-zero patients.

We collected the data of 684 patients with primary HER2-negative breast cancer who underwent surgery between January 2012 and September 2021 from our self-built database. Clinicopathological features, recurrence-free interval (RFI) and breast cancer-specific survival (BCSS) were compared between HER2-low and HER2-zero (IHC 0) patients.

Among the 684 patients, 512 (74.9%) patients had low HER2 expression, and 172 (25.1%) patients had zero HER2 expression. The average age was 57.7 ± 12.6 years, 472 (69.0%) patients were aged < 65 years, and 212 (31.0%) patients were aged ≥ 65 years. Compared to HER2-zero tumors, HER2-low tumors had a higher proportion of hormone receptor (HR)-positive cases (89.6% vs. 75.6%, P < 0.001) and a lower rate of histological grade III cases (29.4% vs. 38.8%, P < 0.001). Kaplan-Meier analysis showed that low HER2 expression was associated with prolonged RFI in breast cancer patients, especially in HR + breast cancer patients (P = 0.028) and < 65-year-old breast cancer patients (P = 0.000). Multivariate Cox regression analysis showed that low HER2 expression was a low-risk factor for RFI (HR: 0.531, 95% CI: 0.292-0.967, P = 0.038) but had no influence on BCSS (P = 0.272).

HER2-low tumors had a higher proportion of HR positivity and a lower rate of histological grade III than HER2-zero tumors. Low HER2 expression seemed to be a protective factor for RFI, especially in patients with HR + and those younger than 65 years.