Cancer Res Treat.  2023 Oct;55(4):1210-1221. 10.4143/crt.2022.1633.

Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy

• Ma Y
• Zhu M
• Zhang J
• Lv M
• Chen X
• Liu Z

• KMID: 2547795
• DOI: http://doi.org/10.4143/crt.2022.1633

Abstract

Purpose
Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT).
Materials and Methods
The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined.
Results
Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016).
Conclusion
Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Keyword

Breast neoplasms; Prognostic value; Evolution; HER2-low; HER2 gain; Disease-free survival; Neoadjuvant therapy

Figure

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  Fig. 1 Distribution and pathological complete response (pCR) rates of study population. (A) Distribution of study population according to hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. (B) pCR rates according to HER2 status in all, HR-negative, and HR-positive patients.

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  Fig. 2 Kaplan-Meier survival analysis for disease-free survival according to pre-NACT human epidermal growth factor receptor 2 (HER2) status (A) and pathological complete response (pCR) status (B) in all, hormone receptor (HR)–negative (C), and HR-positive (D) patients.

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  Fig. 3 Evolution of human epidermal growth factor receptor 2 (HER2) status from primary breast cancer (BC) tumors to residual diseases after neoadjuvant chemotherapy (NACT) in all (A), hormone receptor (HR)–negative (B), and HR-positive (C) patients.

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  Fig. 4 Human epidermal growth factor receptor 2 (HER2) status and disease-free survival analysis after neoadjuvant chemotherapy (NACT). (A) Distribution of HER2-positive according to hormone receptor (HR) and HER2 status before NACT. (B) The impact on disease-free survival events rate of HER2 gain and targeted therapy. (C) Kaplan-Meier survival analysis for disease-free survival according to HER2 status after NACT (HER2-positve 87.9% vs. HER2-negative maintained 79.5%; p=0.048). (D) Kaplan-Meier survival analysis for disease-free survival according to targeted therapy in HER2-positive patients after NACT.

Reference

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