J Breast Cancer.  2019 Mar;22(1):120-130. 10.4048/jbc.2019.22.e1.

Central Nervous System Failure in Korean Breast Cancer Patients with HER2-Enriched Subtype: Korean Radiation Oncology Group 16-15 Multicenter Retrospective Study

• Kim K
• Shin KH
• Kim JH
• Choi DH
• Park W
• Kim YB
• Kim HJ
• Kim JH
• Park H
• Lee SY
• Kim J
• Oh DH
• Kim IA

• KMID: 2441857
• DOI: http://doi.org/10.4048/jbc.2019.22.e1

Abstract

PURPOSE
The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT).
METHODS
A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%).
RESULTS
The median follow-up duration was 84 (range, 8-171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076-4.746; p = 0.031).
CONCLUSION
Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.

Keyword

Breast Neoplasms; Central Nervous System Neoplasms; ERBB2 Protein; Radiotherapy; Trastuzumab

MeSH Terms

Brain
Breast Neoplasms*
Breast*
Central Nervous System Neoplasms
Central Nervous System*
Chemotherapy, Adjuvant
Disease-Free Survival
Drug Therapy
Follow-Up Studies
Humans
Mastectomy
Multivariate Analysis
Neoplasm Metastasis
Quality of Life
Radiation Oncology*
Radiotherapy
Receptor, Epidermal Growth Factor
Retrospective Studies*
Survival Rate
Trastuzumab
Receptor, Epidermal Growth Factor
Trastuzumab

Figure

• 

  Figure 1 DFS and OS curves for all patients. DFS = disease-free survival; OS = overall survival.

• 

  Figure 2 (A) DFS and (B) OS curves according to trastuzumab receipt. DFS = disease-free survival; OS = overall survival.

• 

  Figure 3 CNS-relapse free survival curves according to trastuzumab receipt. CNS = central nervous system.

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