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. 2025 Jun;32(6):4008-4016.
doi: 10.1245/s10434-025-17110-5. Epub 2025 Mar 11.

Serum Enzymes and Pathologic Complete Response to the Addition of Targeted Therapy in Neoadjuvant Chemotherapy for HER2-Positive Breast Cancer Patients

Zongshun Chen  1   2 , Jing Zhang  3 , Wei Chen  1   2 , Xueyi Chen  2   4 , Da-Lin Lu  5 , Junjie Li  6
Affiliations

Serum Enzymes and Pathologic Complete Response to the Addition of Targeted Therapy in Neoadjuvant Chemotherapy for HER2-Positive Breast Cancer Patients

Zongshun Chen et al. Ann Surg Oncol. 2025 Jun.

Abstract

Background: This study investigated the association between circulating alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) and the pathologic complete response (pCR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant chemotherapy with trastuzumab (H) and pertuzumab (P).

Methods: Data were collected from 290 patients with HER2-positive breast cancer at Sichuan Cancer Hospital between August 2019 and August 2023. Blood samples were collected to assess the serum enzyme levels, including ALT, AST, CK, LDH, and GGT. Univariable analysis was first performed, followed by multivariable logistic regression, to assess the association of pCR with ALT, AST, CK, LDH, and GGT levels before and after neoadjuvant chemotherapy with H and P.

Results: Of the 290 patients, 174 (60%) achieved pCR after neoadjuvant chemotherapy combined with dual-target therapy. Multivariable logistic regression analysis showed that lower ALT and GGT levels, higher ALT levels before treatment (odds ratio [OR], 2.02; 95% confidence interval [CI] 1.11-3.67; p = 0.02), and higher GGT levels after treatment (OR, 2.04; 95% CI 1.14-3.66; p = 0.017) were significantly associated with pCR. Additionally, neoadjuvant chemotherapy combined with H and P dual-target therapy increased ALT, AST, LDH, and GGT levels in patients' blood.

Conclusion: Before neoadjuvant chemotherapy combined with H and P dual-target therapy, ALT levels were associated with pCR. After the treatment, GGT levels were linked to pCR. This treatment regimen was associated with increased blood levels of ALT, AST, LDH, and GGT.

Keywords: Dual-targeted therapy; HER2 positive breast cancer; Neoadjuvant chemotherapy; Pathological complete response; Pertuzumab; Serum enzymes; Trastuzumab.

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Conflict of interest statement

Disclosure: The authors declare that they have no conflict of interest. Ethics Approval: This study was approved by the Ethics Committee of Medical Research and Medical New Technology of Sichuan Cancer Hospital, consistent with the principles of the Declaration of Helsinki. Informed consent was obtained from all participants for this study. Consent for publication: Consent for publication was obtained from the participants.

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