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Association between prolonged metastatic free interval and recurrent metastatic breast cancer survival: findings from the SEER database

  • Epidemiology
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The prevalence of patients living with prolonged interval between initial breast cancer diagnosis and development of subsequent metastatic disease may be increasing with improved treatment. In order to counsel these patients as to their prognosis, we investigated the association between metastatic free interval (MFI) and subsequent survival from newly diagnosed metastatic breast cancer (MBC) in a population-level U.S. cohort.


The Surveillance, Epidemiology and End Results database was used to identify patients with both an initial stage 1–3 breast cancer diagnosis and subsequent MBC diagnosis recorded from 1988 to 2014. Patients were stratified by MFI (< 5 years, 5–10 years, > 10 years). The association between MFI and metastatic breast cancer-specific mortality (MBCSM) was analyzed with Fine–Gray competing risks regression.


Five-year recurrent metastatic breast cancer-specific survival rate was 23%, 26%, and 35% for patients with MFI < 5, 5–10, and > 10 years, respectively. Patients with > 10 year MFI were less likely to die of breast cancer when compared with a referent group with < 5 years MFI (standard hazard ratio (SHR) 0.77 [95% CI 0.65–0.90] P < 0.001). There was no significant difference for patients with MFI of 5–10 years (SHR 0.92 [95% CI 0.81–1.04, P 0.191]) compared to < 5 years. Other prognostic factors like White race, lower tumor grade, and ER/PR-positive receptors were also associated with improved cancer-specific survival after diagnosis of MBC.


Prolonged MFI greater than 10 years between initial breast cancer diagnosis and subsequent metastatic disease was found to be associated with improved recurrent MBC 5-year survival and decreased risk of breast cancer-specific mortality. This has potential implications for counseling patients as to prognosis, choice of treatment, as well as the stratification of patients considered for MBC clinical trials.

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Enoch Chang was supported by the NIDDK of the NIH under Award Number T35DK104689. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations



Enoch Chang: Conceptualization, data curation, formal statistical analysis and interpretation of data, funding acquisition, investigation, methodology, software, validation, visualization, writing—original draft, and writing—review and editing. Sarah S. Mougalian: Analysis and interpretation of data, writing—review and editing. Kerin B. Adelson: Analysis and interpretation of data, writing—review and editing. Melissa R. Young: Analysis and interpretation of data, writing—review and editing. James B. Yu: Conceptualization, data curation, formal statistical analysis and interpretation of data, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing—original draft, and writing—review and editing.

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Correspondence to James B. Yu.

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Conflict of interest

Sarah S. Mougalian MD: Consulting role with Eisai. Stocks: Gilead, Coronado Biosciences, Roche. Research funding from Genentech, Pfizer; Kerin B. Adelson MD: Immediate family member is employed with Lyra Health; Consulting role with Wellpoint; Travel, Accommodations, Expenses from Genentech; Honoraria from Genentech; James B. Yu MD, MHS: Consulting role with Augmenix. Research funding from twenty-first Century Oncology.

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Chang, E., Mougalian, S.S., Adelson, K.B. et al. Association between prolonged metastatic free interval and recurrent metastatic breast cancer survival: findings from the SEER database. Breast Cancer Res Treat 173, 209–216 (2019).

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