Prognostic impact of reduced HER2 protein expression in post-neoadjuvant therapy resection specimens: A single institution experience and review of the literature

Authors

Jan Paredes Mogica, Department of Oncology, Yale-New Haven Health Bridgeport Hospital, Bridgeport, CT, USA.
Haiming Tang, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Yuanxin Liang, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Minghao Zhong, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Pei Hui, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Malini Harigopal, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Uma Krishnamurti, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Neal A. Fischbach, Department of Oncology, Yale University School of Medicine, New Haven, CT, USA.
Haiying Zhan, Department of Pathology, Yale University School of Medicine, New Haven, CT, USA. Electronic address: haiying.zhan@yale.edu.

Document Type

Article

Publication Title

Breast (Edinburgh, Scotland)

Abstract

BACKGROUND: Retesting for Human epidermal growth factor receptor-2 (HER2) in post-neoadjuvant therapy resection is variable, and data is conflicting regarding the prognostic significance of changes in HER2 expression pre and post therapy. METHODS: We identified 104 patients with localized HER2 IHC 3+ breast cancer who received neoadjuvant trastuzumab(T)/pertuzumab(P) containing chemotherapy at Yale Cancer Center between 2012 and 2022. Patients were divided into 3 cohorts by response and HER2 IHC in the residual disease: Cohort 1 pathologic complete response (pCR), Cohort 2 pre-treatment IHC 3+/post treatment IHC 1+/2+, and Cohort 3 pre-treatment IHC 3+/post-treatment IHC 3+. Kaplan-Meier survival analysis was performed to assess recurrence free survival at 36 months. RESULTS: The overall pCR rate was 62.5% (65/104), while 37.5% (39/104) of patients had residual disease (RD). Among patients with RD, 58.9% (23/39) remained IHC 3+ and 41.1% (16/39) had reduced HER2 expression IHC1+ or 2+. In patients with HER2 IHC 3+ RD, 26% (6/23) developed local recurrence or distant metastasis while none of patients with post NAT HER2 IHC 1+ or 2+ RD had relapse (p = 0.0309). In patients with pCR, 6.15% (4/65) had recurrence. Kaplan-Meier survival analysis revealed superior disease-free survival in patients with reduced HER2 IHC expression compared to those with remained IHC 3+ (log rank p = 0.004). CONCLUSION: We conclude that reduced HER2 expression by IHC following neoadjuvant treatment was associated with lower recurrence rates in HER2 IHC 3+ breast cancer. If confirmed, RD HER2 IHC expression could be used as a prognostic biomarker to stratify patients in adjuvant trials and identify patients who may benefit from more intensive adjuvant therapy and post therapy surveillance.

First Page

103586

DOI

10.1016/j.breast.2023.103586

Publication Date

12-1-2023

Recommended Citation

Mogica, Jan Paredes; Tang, Haiming; Liang, Yuanxin; Zhong, Minghao; Hui, Pei; Harigopal, Malini; Krishnamurti, Uma; Fischbach, Neal A.; and Zhan, Haiying, "Prognostic impact of reduced HER2 protein expression in post-neoadjuvant therapy resection specimens: A single institution experience and review of the literature" (2023). Internal Medicine. 204.
https://scholar.bridgeporthospital.org/internal_medicine/204

Identifier

37812963 (pubmed); PMC10568274 (pmc); 10.1016/j.breast.2023.103586 (doi); S0960-9776(23)00562-3 (pii)