title: Metastasis-Free Interval Is Closely Related to Tumor Characteristics and Has Prognostic Value in Breast Cancer Patients with Distant Relapse.
abstract: OBJECTIVE
  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 (≥2 years and <5 years), or long (≥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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hee Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sung Gwe
authors.initials: SG
authors.lastname: Ahn
authors.affiliation: Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hak Min
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jong Tae
authors.initials: JT
authors.lastname: Park
authors.affiliation: Biostatistics Collaboration Unit, Gangnam Medical Research Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyunghwa
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
authors.forename: Seung Ah
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Jeong
keywords: Breast neoplasms; Metastasis; Prognostic factor; Subtypes