J Breast Cancer.  2018 Mar;21(1):45-50. 10.4048/jbc.2018.21.1.45.

FcrR3A-158 Polymorphism and Stromal Tumor-Infiltrating Lymphocytes and Survival among Patients with Metastatic HER2-Positive Breast Cancer Receiving Trastuzumab-Based Treatment

• Chae H
• Yoo C
• Yoon JA
• Lee HJ
• Kim KP
• Kim JE
• Ahn JH
• Jung KH
• Gong G
• Kim SB

• KMID: 2441867
• DOI: http://doi.org/10.4048/jbc.2018.21.1.45

Abstract

PURPOSE
The prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has markedly improved since the introduction of trastuzumab. We aimed to evaluate the association between stromal tumor-infiltrating lymphocyte (sTIL) or FcrR polymorphisms and survival among patients with metastatic HER2-positive breast cancer who were treated with trastuzumab.
METHODS
A total of 56 women with recurrent or metastatic HER2-positive breast cancer who received the trastuzumab-taxane combination as first-line treatment were included in this retrospective analysis. The single-step multiplex allele-specific real-time polymerase chain reaction technique was employed for FcrR3A genotyping. sTILs were identified via immunohistochemical analysis of surgical (n=34, 60.7%) or biopsy specimens of metastatic lesions (n=22, 39.3%).
RESULTS
We classified patients based on the sTIL level (≤10% [n=44] or >10% [n=12]); high sTIL counts were more commonly observed in patients with hormone receptor-negative tumors than in those with hormone receptor-positive tumors (34.8% vs. 12.1%, p=0.02). There was a significant association between high sTIL levels and longer progression-free survival in comparison to low sTIL levels (median, 28.4 months vs. 16.8 months; p=0.03). With regard to the FcrR3A-158 genotype, patients were classified into the Phenylalanine/Phenylalanine group (23 patients, 41.1%), Phenylalanine/Valine group (23 patients, 41,1%), or Valine/Valine group (10 patients, 17.9%); these classifications were not associated with clinical outcomes.
CONCLUSION
High sTIL expression may be associated with better efficacy of trastuzumab-containing therapy in patients with metastatic HER2-positive breast cancer. However, this finding warrants further evaluation in the larger population.

Keyword

Breast neoplasms; ErbB-2 receptor; Trastuzumab; Tumor infiltrating lymphocytes

MeSH Terms

Biopsy
Breast Neoplasms*
Breast*
Classification
Disease-Free Survival
Female
Genotype
Humans
Lymphocytes, Tumor-Infiltrating*
Prognosis
Real-Time Polymerase Chain Reaction
Receptor, Epidermal Growth Factor
Receptor, ErbB-2
Retrospective Studies
Trastuzumab
Receptor, Epidermal Growth Factor
Receptor, ErbB-2
Trastuzumab

Figure

• 

  Figure 1 Survival outcomes according to the presence of FcrR3A polymorphisms. Both progression-free survival (A) and overall survival (B) did not differ between the F/F, F/V, and V/V group with p-value of 0.32 and 0.12, respectively.F/F=phenylalanine/phenylalanine; F/V=phenylalanine/valine; V/V=valine/valine.

• 

  Figure 2 Survival outcomes according to the level of stromal tumor-infiltrating lymphocytes (sTIL). The high sTIL group was significantly associated with a longer progression-free survival (A) compared to the low sTIL group (28.4 months [95% CI, 21.7–35.0] vs. 16.8 months [95% CI, 11.1–22.6]; p=0.03). On the other hand, the high sTIL showed a marginal relationship with better overall survival (B) without statistical significance (vs. low sTIL; 75.9 months [95% CI, 22.8–129.0] vs. 56.9 months [95% CI, 27.3–86.5]; p=0.58).CI=confidence interval.

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