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

  • Epidemiology
  • Published:
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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgements

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

Funding

The study received financial support from Amgen Incorporated.

Author information

Authors and Affiliations

  1. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Alle 43-45, 8200, Aarhus N, Denmark

    Deirdre Cronin-Fenton, Anders Kjærsgaard, Mette Nørgaard & Henrik T. Sørensen

  2. Amgen Incorporated, Thousand Oaks, CA, USA

    Justyna Amelio, Alexander Liede & Rohini K. Hernandez

Authors
  1. Deirdre Cronin-Fenton
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  2. Anders Kjærsgaard
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  3. Mette Nørgaard
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  4. Justyna Amelio
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  5. Alexander Liede
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  6. Rohini K. Hernandez
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  7. Henrik T. Sørensen
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Contributions

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.

Corresponding author

Correspondence to Deirdre Cronin-Fenton.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

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

Appendix

Appendix

Breast cancer recurrence algorithm:

  1. 1.

    DNRP-registered or DCR-registered metastases code (ICD10: DC76–DC80) 180 or more days after first breast cancer surgery, and without a new primary cancer diagnosis registered in the DNRP or DCR between the date of the first breast cancer surgery and the date of the DNRP or DCR metastases code. Here and below, a new primary cancer was defined as a new cancer that is different from non-melanoma skin cancer (ICD10 C44).

  2. 2.

    Pathology Registry SNOMED combinations recorded 180 or more days after first breast cancer surgery, and without a new primary cancer diagnosis registered in the DNRP or DCR. Combinations were (1) T code (topography/location) in the breast (T04000-T09420) with morphology codes M8 or M9 with ≥3 in the fifth position (e.g., M8XXX3), (2) any T code with morphology codes M8 or M9 with the numbers 4, 6, or 7 in the fifth position.

  3. 3.

    A code specific for local breast cancer recurrence in the DNRP any time after primary diagnosis: DC509X (these codes have only been used in DNRP beginning in 2012). A code for “recurrence operation” (KHAF) in the DNRP any time after diagnosis.

We used the DC509X code to distinguish local from non-local recurrent disease.

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Cronin-Fenton, D., Kjærsgaard, A., Nørgaard, M. et al. Breast cancer recurrence, bone metastases, and visceral metastases in women with stage II and III breast cancer in Denmark. Breast Cancer Res Treat 167, 517–528 (2018). https://doi.org/10.1007/s10549-017-4510-3

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  • DOI: https://doi.org/10.1007/s10549-017-4510-3

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