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

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Abstract

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.

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Data availability

The data from this study are available on request to the authors.

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Funding

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).

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Authors and Affiliations

  1. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea

    Min Hwan Kim, Gun Min Kim & Joohyuk Sohn

  2. Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

    Jee Hung Kim

  3. Division of Breast Surgery, Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea

    Jee Ye Kim, Hyung Seok Park, Seho Park, Young Up Cho, Byeong Woo Park & Seung Il Kim

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  1. Min Hwan Kim
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Contributions

MHK and JS conceived and designed the study. MHK and JS performed analysis and interpretation of the data and wrote the manuscript. MHK, GMK, JHK, and JS contributed to metastatic breast cancer database administration, and JYK, HSP SP, YUC, BWP, and SIK contributed to early breast cancer database administration. All authors were involved in clinical care of the enrolled patients, provided study data, and commented on the manuscript. All authors approved the final manuscript.

Corresponding author

Correspondence to Joohyuk Sohn.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board of the Severance Hospital Yonsei University Health System (IRB 4–2016-0574) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants for clinical data collection and investigational use at the time of breast cancer diagnosis in the EBC cohort and at stage IV disease diagnosis in the MBC cohort.

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Kim, M.H., Kim, G.M., Kim, J.H. et al. Intermediate HER2 expression is associated with poor prognosis in estrogen receptor-positive breast cancer patients aged 55 years and older. Breast Cancer Res Treat 179, 687–697 (2020). https://doi.org/10.1007/s10549-019-05505-4

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