J Breast Cancer.  2015 Dec;18(4):371-377. 10.4048/jbc.2015.18.4.371.

Metastasis-Free Interval Is Closely Related to Tumor Characteristics and Has Prognostic Value in Breast Cancer Patients with Distant Relapse

• Kim HJ
• Ahn SG
• Lee HM
• Park JT
• Han K
• Lee SA
• Jeong J

• KMID: 2176286
• DOI: http://doi.org/10.4048/jbc.2015.18.4.371

Abstract

PURPOSE
We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes.
METHODS
We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short (<2 years), intermediate (> or =2 years and <5 years), or long (> or =5 years). Overall survival after metastasis (OSM) was estimated.
RESULTS
Patients with a shorter MFI were younger, more likely to have initial metastasis to visceral organs, and had a larger tumor with a higher stage and grade as well as a higher rate of nodal involvement at initial diagnosis. Among 136 patients with known disease subtypes, shorter MFI was associated with the triple-negative subtype while longer MFI was associated with the hormone receptor-positive/human epidermal growth factor receptor 2 negative subtype. Mortality after metastasis declined sharply with increasing MFI up to approximately 2 years, and continued gradually declining between 2 and 5 years. An MFI longer than 5 years did not add any survival benefit. MFI was a significant prognostic factor for OSM independent of nodal status, stage, metastatic site, and hormone receptor status of the metastasized cancer.
CONCLUSION
MFI is closely related to biological characteristics of both primary tumors and their metastases, and has a prognostic value for survival after metastasis. We therefore suggest investigation into treatments targeting improvement of MFI as a potential novel strategy.

Keyword

Breast neoplasms; Metastasis; Prognostic factor; Subtypes

MeSH Terms

Breast Neoplasms*
Breast*
Diagnosis
Humans
Mortality
Neoplasm Metastasis
Population Characteristics
Receptor, Epidermal Growth Factor
Recurrence*
Receptor, Epidermal Growth Factor

Figure

• 

  Figure 1 Comparison of the mean metastasis-free interval (MFI) according to tumor subtype (p<0.001; one-way analysis of variation test). HR=hormone receptor; HER2=human epidermal growth factor receptor 2; TN=triple-negative.

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  Figure 2 Relationship between the continuous metastasis-free interval (MFI) and the risk of death after metastasis. The solid curve represents the continuous relationship between MFI and the risk of death after metastasis, based on a univariate spline Cox regression model with three knots. Dotted curves represent 95% confidence intervals.

• 

  Figure 3 Kaplan-Meier plots for overall survival after metastasis according to metastasis-free interval (MFI) categories (p<0.001; log-rank test).

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