Prognostic implications of HER2 changes after neoadjuvant chemotherapy in patients with HER2-zero and HER2-low breast cancer

Sora Kang; So Heun Lee; Hee Jin Lee; Hyehyun Jeong; Jae Ho Jeong; Jeong Eun Kim; Jin-Hee Ahn; Kyung Hae Jung; Gyungyub Gong; Hak Hee Kim; Saebyeol Lee; Jongwon Lee; Sung-Bae Kim

doi:10.1016/j.ejca.2023.112956

Prognostic implications of HER2 changes after neoadjuvant chemotherapy in patients with HER2-zero and HER2-low breast cancer

Eur J Cancer. 2023 Sep:191:112956. doi: 10.1016/j.ejca.2023.112956. Epub 2023 Jun 24.

Authors

Affiliations

¹ Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Division of Hemato-Oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
² Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
³ Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
⁴ Department of Radiology, Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
⁵ Division of Breast Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
⁶ Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address: sbkim3@amc.seoul.kr.

PMID: 37473465
DOI: 10.1016/j.ejca.2023.112956

Abstract

Background: The transition of human epidermal growth factor receptor 2 (HER2) status after neoadjuvant chemotherapy (NAC) in HER2-low breast cancer has not been thoroughly evaluated. Here, we evaluated the HER2 transition among HER2-zero and HER2-low breast cancer cases post-NAC and its impact on clinical outcomes.

Methods: We included 1288 patients with HER2-low or zero breast cancer who underwent NAC and surgery between 2014 and 2018 and had paired pre- and post-therapeutic HER2 status results.

Results: Among patients who were HER2-zero pre-NAC (n = 650), 68% and 29% were HER2-zero and HER2-low, respectively, post-NAC. Among patients who were HER2-low pre-NAC (n = 638), 32% of patients showed HER2 changes (low to zero), and 59% of patients had a constant HER2-low status post-NAC. Patients with constant HER2-low or transitions from HER2-low to zero had a higher proportion of hormone receptor positivity (84% and 79%) than those with changes from HER2-zero to low (77%) or with constant HER2-zero (56%), respectively. Multivariable logistic regression analysis revealed that patients with oestrogen receptor positivity had a higher probability of gaining HER2-low expression than those with oestrogen receptor negativity (odds ratio 2.48). No significant differences were observed in terms of overall survival or disease-free survival between patients with and without HER2-changes according to their hormone receptor status, except in the post-therapeutic HER2-low, hormone receptor-negativity subset.

Conclusion: Temporal heterogeneity of HER2-low expression is observed in substantial numbers of post-NAC breast cancer patients. Clinical outcomes show no significant associations, except in the post-therapeutic HER2-low, hormone receptor negativity subset. The prognostic implications of HER2 transition in HER2-low breast cancer require further investigation.

Keywords: HER2-low breast cancer; HER2-zero breast cancer; Neoadjuvant chemotherapy; Prognosis; Temporal heterogeneity.

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Breast Neoplasms*
Chemotherapy, Adjuvant
Disease-Free Survival
Female
Humans
Neoadjuvant Therapy
Prognosis
Receptor, ErbB-2 / metabolism
Receptors, Estrogen / metabolism

Substances

Receptors, Estrogen
Receptor, ErbB-2