The frequency of low HER2 expression in breast cancer and a comparison of prognosis between patients with HER2-low and HER2-negative breast cancer by HR status

Purpose The DESTINY-Breast04 clinical trial is currently investigating whether trastuzumab deruxtecan (T-DXd) is effective in HER2-low as well as HER2-positive breast cancer. This highlights the interest in treatment strategies for patients with HER2-low breast cancer. The current study was therefore designed to determine the frequency of HER2-low among all breast cancers, and to compare the prognosis of HER2-low patients with that of HER2-negative patients. Methods We retrospectively reviewed the biological data from 4,918 of 4,977 primary breast cancer patients who attended our institute. We quantified the overall frequency of breast cancer patients with a new HER2-low subtype that was defined by an immunohistochemistry score of IHC1 + or IHC2 + /ISH-. We then compared the clinical characteristics and prognosis of HER2-low patients with that of patients who did not have HER2 amplification (HER2-0). Results Low HER2 expression was found in 3169 (64.4%) patients; 2860 (58.1%) were HR-positive and 309 (6.3%) were HR-negative. Among HER2-0 patients, 681 (13.9%) were HR-positive and 157 (3.2%) were HR-negative. The HER2-0 group tended to have more poor prognostic factors than the HER2-low group, irrespective of HR status. There were no statistically significant differences between the prognosis of HER2-low and HER2-0 patients, regardless of HR status. However, patients in the HER2-low group tended to have better prognosis than those in the HER2-0 group. Conclusion HER2-low patients did not have a significantly different prognosis than HER2-0 patients, regardless of HR status. However, we should consider tailoring therapies for patients with HRE2-low early breast cancer according to their HR status.

Automated summary

The study retrospectively reviewed data from nearly 5000 primary breast cancer patients to determine the frequency of HER2-low and compare the prognosis of HER2-low patients with HER2-negative patients. The research found that HER2-low patients did not have significantly different prognosis than HER2-0 patients. Tailoring therapies for HER2-low early breast cancer patients based on hormone receptor status may be considered.