De-escalated radiotherapy for HER2-overexpressing breast cancer patients with 1-3 positive lymph nodes undergoing anti-HER2 targeted therapy

Jing Liu; Suning Huang; Zhuofei Bi; Xiaoxue Zhang; Ziqing He; Xiaowen Lan; Yuting Tan; Xiao Lin; Wenyi Zhou; Xiaobo Huang

doi:10.3389/fonc.2023.1280900

De-escalated radiotherapy for HER2-overexpressing breast cancer patients with 1-3 positive lymph nodes undergoing anti-HER2 targeted therapy

Front Oncol. 2023 Nov 1:13:1280900. doi: 10.3389/fonc.2023.1280900. eCollection 2023.

Authors

Jing Liu^#^{1

2

3}, Suning Huang^#⁴, Zhuofei Bi^#^{1

2}, Xiaoxue Zhang^{2

3}, Ziqing He^{1

2

3}, Xiaowen Lan^{1

2

3}, Yuting Tan^{2

3}, Xiao Lin^{2

3}, Wenyi Zhou^{2

3}, Xiaobo Huang^{1

2

3}

Affiliations

¹ Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Centre, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
³ Yat-Sen Breast Tumor Hospital, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
⁴ Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China.

^# Contributed equally.

Abstract

Background: In the era of anti-HER2 targeted therapy, the potential clinical feasibility of considering HER2-overexpressing breast cancer cases presenting with 1-3 positive axillary lymph nodes as low-risk, and thereby contemplating postoperative radiotherapy reduction, remains an important subject for in-depth examination. The aim of this retrospective study was to evaluate the effectiveness of de-escalated radiotherapy in T1-2N1M0 HER2-overexpressing breast cancer patients receiving anti-HER2 targeted therapy. Specifically, omitting regional lymph node irradiation (RNI) after breast-conserving surgery and only performing whole-breast irradiation or omitting postmastectomy radiation therapy.

Methods: A retrospective analysis was conducted on 429 patients with stage T1-2N1M0 primary invasive HER2-overexpressing breast cancer from our center between 2004 and 2018. Patients who received anti-HER2 targeted therapy were divided into an RNI group and a no RNI group to assess the role of RNI. The prognostic role of RNI was investigated via the Kaplan-Meier method and Cox proportional hazards modeling.

Results: The median follow-up time was 46.8 months (range 7.1-225.8 months). In the anti-HER2 targeted therapy group RNI yielded no significant improvements in invasive disease-free survival (IDFS) (p = 0.940), local-regional recurrence-free survival (p = 0.380), distant metastases-free survival (p = 0.698), or overall survival (p = 0.403). Estrogen receptor (ER) status (hazard ratio [HR] 0.105, 95% confidence interval [CI] 0.023-0.749, p = 0.004) and lymph vascular invasion status (LVI) (HR 5.721, 95% CI 1.586-20.633, p = 0.008) were identified as independent prognostic factors for IDFS, and ER-positive and LVI-negative patients exhibited better prognoses.

Conclusion: Omitting RNI may be a safe option in T1-2N1 HER2-overexpressing breast cancer patients receiving standardized anti-HER2 targeted therapy; particularly in ER-positive or LVI-negative subgroups.

Keywords: 1-3 lymph nodes positive; HER2 overexpression; anti-Her2 targeted therapy; early breast cancer; radiotherapy; regional lymph node irradiation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported in part by the Sun Yat-Sen Clinical Research 5010 Program (grant numbers SYS-5010-202303), Sun Yat-Sen Clinical Research Incubation Program (grant numbers SYS-C-202006), Guangzhou Science and Technology Program (grant numbers 2023A03J0723) and Research grants from National Natural Science Foundation of China (grant numbers 82173232).