Breast Cancer Research and Treatment

, Volume 167, Issue 2, pp 517–528 | Cite as

Breast cancer recurrence, bone metastases, and visceral metastases in women with stage II and III breast cancer in Denmark

  • Deirdre Cronin-Fenton
  • Anders Kjærsgaard
  • Mette Nørgaard
  • Justyna Amelio
  • Alexander Liede
  • Rohini K. Hernandez
  • Henrik T. Sørensen



We developed and validated algorithms to identify metastases and breast cancer recurrence in Danish medical registries. We computed the incidence rate (IR) and hazard ratios (HRs) to evaluate predictors of these outcomes in stage II/III breast cancer patients.


We included all women in Denmark diagnosed during 1999–2011 with regional or stage II/III breast cancer. Demographic, tumor, and treatment data were ascertained from population-based health registries. To facilitate diagnostic work-up of the primary cancer, follow-up began 180 days after diagnosis and continued until recurrence/metastases, death, or 31 December 2012, whichever occurred first. We computed the positive predictive values (PPVs) of recurrence, bone metastases, and visceral metastases using medical records as a gold standard. We calculated the cumulative incidence, IR per 10,000 person years, and used Cox regression to compute the HRs and associated 95% confidence intervals (95% CI) for each outcome.


Among 23,478 patients, 7073 had regional stage and 16,405 had stage II/III breast cancer. The PPV for recurrence was 72.6% (95% CI 59.3, 83.3%). The PPVs for bone and visceral metastases were 92.3% (95% CI 69.3–99.2%) and 70.8% (95% CI 51.1, 85.9%), but had low sensitivity. Five-year cumulative incidence of recurrence, bone metastases, and visceral metastases were 18.4, 2.2, and 5.2%, with corresponding 5-year IRs of 540 (95% CI 524, 557), 60 (95% CI 55, 65), and 144 (95% CI 136, 152), respectively. Predictors of recurrence and metastases included age, stage, hormone receptor status, and cancer treatment.


Our algorithms show moderate to high PPVs for recurrence and metastases. The IRs of metastases were lower compared with other registry-based cohort studies, so may be underestimated in Danish registries.


Breast cancer Breast cancer recurrence Incidence rate Bone metastases Visceral metastases Mortality 



The authors thank Henriette Kristoffersen and Hanne M. Madsen for reviewing medical records.


The study received financial support from Amgen Incorporated.

Authors’ contribution

DCF, AK, and MN have no disclosures. HTS has not received any personal grants; this study was partly supported by a grant to Clinical Institute, Aarhus University Hospital. JA was an employee and stock owner at Amgen at the time of completion of this study, and is currently employed and owns stock at GSK. AL and RKH are employees and own stock at Amgen, Inc.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

This study was approved by the Danish Data Protection Agency ( 2014-41-3250) and the Danish Health Board ( 3-3013-670/1/). Under Danish law, informed consent is not required for registry-based research.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Deirdre Cronin-Fenton
    • 1
  • Anders Kjærsgaard
    • 1
  • Mette Nørgaard
    • 1
  • Justyna Amelio
    • 2
  • Alexander Liede
    • 2
  • Rohini K. Hernandez
    • 2
  • Henrik T. Sørensen
    • 1
  1. 1.Department of Clinical EpidemiologyAarhus University HospitalAarhus NDenmark
  2. 2.Amgen IncorporatedThousand OaksUSA

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