Intermediate HER2 expression is associated with poor prognosis in estrogen receptor-positive breast cancer patients aged 55 years and older

Min Hwan Kim, Gun Min Kim, Jee Hung Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Young Up Cho, Byeong Woo Park, Seung Il Kim, Joohyuk Sohn

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Purpose: An antibody–drug conjugate targeting HER2, DS8201, has shown clinical activity against breast cancer with low-level HER2 expression. We aimed to evaluate the prognostic impact of intermediate HER2 expression in estrogen receptor (ER)+ early breast cancer (EBC) and metastatic breast cancer (MBC) cohorts. Methods: We analyzed prospectively collected data from EBC and MBC cohorts at Yonsei Cancer Center. Patients with HER2 immunohistochemistry (IHC) 0 ~ 1+ were assigned to the HER2-negative group, and patients with IHC 2+ and in situ hybridization (ISH)-negativity were assigned to the HER2-intermediate group. After the exclusion of HER2 IHC 3+ or ISH+ patients, a total of 2657 EBC and 535 MBC patients were analyzed. Results: In total, 654 (24.6%) EBC and 166 (31.0%) MBC patients were classified in the HER2-intermediate group. The HER2-intermediate patients more frequently tended to have progesterone receptor (PR)-negativity and higher nuclear grade in the EBC cohort, and showed a higher proportion of patients aged ≥ 55 years compared with the HER2-negative group in the MBC cohort. The HER2-intermediate patients showed significantly poorer recurrence-free survival (RFS) compared to the HER2-negative patients in the EBC cohort (p = 0.044). Notably, intermediate HER2 expression predicted poorer RFS in EBC patients aged ≥ 55 years (hazard ratio 1.95; p = 0.042) in multivariate Cox analysis but did not affect RFS in those aged < 55 years. In line with the EBC cohort results, intermediate HER2 expression predicted poorer overall survival (OS) in MBC patients aged ≥ 55 (hazard ratio 1.45; p = 0.044) without affecting OS of those aged < 55 years. Conclusion: Intermediate HER2 expression is an independent predictor of poor prognosis in both ER+ EBC and MBC patients aged ≥ 55 years. The clinical efficacy of new HER2-targeting antibody–drug conjugates needs to be validated in this high-risk subset of ER+ breast cancer patients.

Original languageEnglish
Pages (from-to)687-697
Number of pages11
JournalBreast Cancer Research and Treatment
Issue number3
Publication statusPublished - 2020 Feb 1

Bibliographical note

Funding Information:
This study was supported by a Grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (Grant No. HA17C0055).

Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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