Clinical & Experimental Metastasis

, Volume 34, Issue 8, pp 457–465 | Cite as

De novo metastasis in breast cancer: occurrence and overall survival stratified by molecular subtype

  • David J. Press
  • Megan E. Miller
  • Erik Liederbach
  • Katherine Yao
  • Dezheng Huo
Research Paper


Breast cancer molecular subtypes, categorized jointly by hormone receptors (HR) and human epidermal growth factor-2 (HER2), are utilized to guide systemic therapy. We hypothesized distinct patterns of de novo metastasis and overall survival by molecular subtype using a retrospective cohort of 399,772 women in the National Cancer Database diagnosed with first primary invasive breast cancer between 2010 and 2014, of whom 13,924 were diagnosed with de novo metastasis from 2010 to 2013 and had follow up data. The relationship of molecular subtype with patient and tumor characteristics, including site of de novo metastasis, were examined using Chi-squared tests. Kaplan–Meier and Cox proportional hazards analyses were used to examine overall survival by molecular subtype. Bone was the most frequent de novo metastatic site for all molecular subtypes. Compared to HR+/HER2−, patients with HR−/HER2+ experienced 4.5, 3.0, and 6.0 times the de novo brain, lung, and liver metastasis respectively. In survival analyses of women diagnosed with de novo metastasis, the mortality risk relative to HR+/HER2− was twice as high for triple-negative (hazard ratio = 2.02, 95% CI 1.89–2.16) and modestly lower for HR+/HER2+ (hazard ratio = 0.83, 95% CI 0.78–0.88). The median survival difference between metastatic patients with and without chemotherapy was 28.6 months in HR+/HER2+ and 28.2 months in HR−/HER2+, but only 10.9 months in triple-negative and 5.2 months in HR+/HER2−. In conclusion, despite unfavorable patterns of de novo metastasis, HER2+ breast cancers had relatively better survival in recent years, probably due to treatment differences. Utilizing molecular subtype and site of de novo metastasis may predict prognosis and guide treatment.


Breast cancer Subtypes Metastasis Survival Epidemiology 



American Joint Committee on Cancer


Commission on Cancer


Confidence intervals


Estrogen receptor


Hormone receptor


Human epidermal growth factor receptor 2-neu


International Classification of Diseases for Oncology-Third edition


National Cancer Database




Overall survival


Progesterone receptor



This research was supported by Susan G. Komen® (GTDR16376189) and American Cancer Society (MRSG-13-063-01-TBG).

Compliance with ethical standards

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10585_2017_9871_MOESM1_ESM.docx (73 kb)
Supplementary material 1 (DOCX 73 KB)


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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  • David J. Press
    • 1
  • Megan E. Miller
    • 2
  • Erik Liederbach
    • 3
  • Katherine Yao
    • 3
  • Dezheng Huo
    • 1
  1. 1.Department of Public Health SciencesThe University of ChicagoChicagoUSA
  2. 2.Department of SurgeryCase Western Reserve University HospitalsClevelandUSA
  3. 3.Department of SurgeryNorthShore University HealthSystemEvanstonUSA

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