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

Breast Cancer. 2022 Mar;29(2):234-241. doi: 10.1007/s12282-021-01303-3. Epub 2021 Oct 7.


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.

Keywords: HER2-0; HER2-low; Low HER2 expression breast cancer; Prognosis; Trastuzumab deruxtecan.

MeSH terms

  • Breast Neoplasms* / chemically induced
  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Immunohistochemistry
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Retrospective Studies
  • Trastuzumab / therapeutic use


  • Receptor, ErbB-2
  • Trastuzumab