Skip to main content

Advertisement

SpringerLink
Log in

Site of metastasis and breast cancer mortality: a Danish nationwide registry-based cohort study

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Survival among patients with metastatic breast cancer may vary according to the site of metastasis and receptor status. We used Danish nationwide medical registries to establish a cohort of patients with metastatic breast cancer (870 with de novo metastatic disease and 3518 with recurrent disease with distant metastasis) diagnosed during 1997–2011. We examined 1-year and >1 to 5-year mortality associated with first site of metastasis and receptor expression status of the primary tumor. Cox proportional regression was used to compute confounder-adjusted mortality rate ratios (MRRs) associated with site of metastasis, stratified by receptor status. Overall 1-year and >1 to 5-year mortality risks were 36 and 69 %, respectively. Risk of death within 1 year was highest for brain-only (62 %) and liver-only (43 %) involvement and nearly the same for patients with lung-only (32 %), bone-only (32 %) involvement, and other/combination of sites (34 %). Using bone-only metastasis as reference, women with brain-only metastasis had more than two-fold increased risk of dying. The adjusted MRR for women with liver-only metastasis also was increased, though less pronounced. Patients with lung-only [adjusted MRR 0.9 (95 % confidence interval (CI) 0.8, 1.1)] or other metastases [adjusted MRR 1.0 (95 % CI 0.9, 1.2)] had similar mortality as patients with bone-only metastasis. Positive hormonal receptor status was a favorable prognostic factor. Metastatic breast cancer has a serious prognosis. Patients with brain-only metastasis had the highest mortality. Positive hormonal receptor status on the primary tumor was a favorable prognostic factor for all metastatic sites.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CCI:

Charlson Comorbidity Index

CI:

Confidence interval

DCR:

The Danish Cancer Registry

DNPR:

The Danish National Patient Registry

ICD:

International Classification of Diseases

MRR:

Mortality rate ratio

TNM:

Classification of malignant tumours

References

  1. Ruiterkamp J, Ernst MF, de Munck L, van der Heiden-van der Loo M, Bastiaannet E, van de Poll-Franse LV, Bosscha K, Tjan-Heijnen VC, Voogd AC (2011) Improved survival of patients with primary distant metastatic breast cancer in the period of 1995–2008. A nationwide population-based study in the Netherlands. Breast Cancer Res Treat 128:495–503

    Article  CAS  PubMed  Google Scholar 

  2. Saphner T, Tormey DC, Gray R (1996) Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol 14:2738–2746

    CAS  PubMed  Google Scholar 

  3. Muss HB, Case LD, Richards F II, White DR, Cooper MR, Cruz JM, Powell BL, Spurr CL, Capizzi RL (1991) Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association. N Engl J Med 325:1342–1348

    Article  CAS  PubMed  Google Scholar 

  4. Norton L (1991) Metastatic breast cancer. Length and quality of life. N Engl J Med 325:1370–1371

    Article  CAS  PubMed  Google Scholar 

  5. Andre F, Slimane K, Bachelot T, Dunant A, Namer M, Barrelier A, Kabbaj O, Spano JP, Marsiglia H, Rouzier R, Delaloge S, Spielmann M (2004) Breast cancer with synchronous metastases: trends in survival during a 14-year period. J Clin Oncol 22:3302–3308

    Article  PubMed  Google Scholar 

  6. Dawood S, Broglio K, Ensor J, Hortobagyi GN, Giordano SH (2010) Survival differences among women with de novo stage IV and relapsed breast cancer. Ann Oncol 21:2169–2174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. de Glas NA, Bastiaannet E, de Craen AJ, van de Velde CJ, Siesling S, Liefers GJ, Portielje JE (2015) Survival of older patients with metastasised breast cancer lags behind despite evolving treatment strategies—a population-based study. Eur J Cancer 51:310–316

    Article  PubMed  Google Scholar 

  8. Lobbezoo DJ, van Kampen RJ, Voogd AC, Dercksen MW, van den Berkmortel F, Smilde TJ, van de Wouw AJ, Peters FP, van Riel JM, Peters NA, de Boer M, Peer PG, Tjan-Heijnen VC (2015) Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer? Br J Cancer 112:1445–1451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ho VK, Gijtenbeek JM, Brandsma D, Beerepoot LV, Sonke GS, van der Heiden-van der Loo M (2015) Survival of breast cancer patients with synchronous or metachronous central nervous system metastases. Eur J Cancer 51:2508–2516

    Article  CAS  PubMed  Google Scholar 

  10. Gerratana L, Fanotto V, Bonotto M, Bolzonello S, Minisini AM, Fasola G, Puglisi F (2015) Pattern of metastasis and outcome in patients with breast cancer. Clin Exp Metastasis 32:125–133

    Article  CAS  PubMed  Google Scholar 

  11. Solomayer EF, Diel IJ, Meyberg GC, Gollan C, Bastert G (2000) Metastatic breast cancer: clinical course, prognosis and therapy related to the first site of metastasis. Breast Cancer Res Treat 59:271–278

    Article  CAS  PubMed  Google Scholar 

  12. Frank L (2000) Epidemiology. When an entire country is a cohort. Science 287:2398–2399

    Article  CAS  PubMed  Google Scholar 

  13. Storm HH, Michelsen EV, Clemmensen IH, Pihl J (1997) The Danish Cancer Registry—history, content, quality and use. Dan Med Bull 44:535–539

    CAS  PubMed  Google Scholar 

  14. Gjerstorff ML (2011) The Danish Cancer Registry. Scand J Public Health 39:42–45

    Article  PubMed  Google Scholar 

  15. Bjerregaard B, Larsen OB (2011) The Danish Pathology Register. Scand J Public Health 39:72–74

    Article  PubMed  Google Scholar 

  16. Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sorensen HT (2015) The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 7:449–490

    Article  PubMed  PubMed Central  Google Scholar 

  17. Blichert-Toft M, Christiansen P, Mouridsen HT (2008) Danish Breast Cancer Cooperative Group–DBCG: history, organization, and status of scientific achievements at 30-year anniversary. Acta Oncol 47:497–505

    Article  PubMed  Google Scholar 

  18. Jensen AR, Overgaard J, Storm HH (2002) Validity of breast cancer in the Danish Cancer Registry. A study based on clinical records from one county in Denmark. Eur J Cancer Prev 11:359–364

    Article  CAS  PubMed  Google Scholar 

  19. Jensen AO, Norgaard M, Yong M, Fryzek JP, Sorensen HT (2009) Validity of the recorded International Classification of Diseases, 10th edition diagnoses codes of bone metastases and skeletal-related events in breast and prostate cancer patients in the Danish National Registry of Patients. Clin Epidemiol 1:101–108

    Article  PubMed  PubMed Central  Google Scholar 

  20. Youlden DR, Cramb SM, Dunn NA, Muller JM, Pyke CM, Baade PD (2012) The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer Epidemiol 36:237–248

    Article  PubMed  Google Scholar 

  21. Venur VA, Leone JP (2016) Targeted therapies for brain metastases from breast cancer. Int J Mol Sci. doi:10.3390/ijms17091543

    PubMed  PubMed Central  Google Scholar 

  22. Dawood S, Broglio K, Esteva FJ, Ibrahim NK, Kau SW, Islam R, Aldape KD, Yu TK, Hortobagyi GN, Gonzalez-Angulo AM (2008) Defining prognosis for women with breast cancer and CNS metastases by HER2 status. Ann Oncol 19:1242–1248

    Article  CAS  PubMed  Google Scholar 

  23. Lorusso G, Ruegg C (2012) New insights into the mechanisms of organ-specific breast cancer metastasis. Semin Cancer Biol 22:226–233

    Article  CAS  PubMed  Google Scholar 

  24. Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, Wei S (2015) Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol 143:471–478

    Article  PubMed  Google Scholar 

  25. Vaz-Luis I, Lin NU, Keating NL, Barry WT, Lii H, Winer EP, Freedman RA (2015) Racial differences in outcomes for patients with metastatic breast cancer by disease subtype. Breast Cancer Res Treat 151:697–707

    Article  PubMed  Google Scholar 

  26. Lin NU, Amiri-Kordestani L, Palmieri D, Liewehr DJ, Steeg PS (2013) CNS metastases in breast cancer: old challenge, new frontiers. Clin Cancer Res 19:6404–6418

    Article  CAS  PubMed  Google Scholar 

  27. Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, Costa A, Winer EP, Cardoso F, Task Force ESO-MBC (2010) International guidelines for management of metastatic breast cancer: can metastatic breast cancer be cured? J Natl Cancer Inst 102:456–463

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author contribution

HTS and AGO conceived the study idea and designed the study. HTS and UHJ established and designed the cohort. AGO reviewed the literature and directed the study-specific analyses together with HTS, which were carried out by UHJ. All authors participated in the discussion and interpretation of the results. AGO organised the writing and wrote the initial drafts. All authors critically revised the manuscript for intellectual content and approved the final version. HTS is the guarantor for the article and accepts full responsibility for the work and the conduct of the study, had access to the data, and oversaw the decision to publish.

Funding

The study was funded by the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation and administered by the Danish Regions, and by the Danish Cancer Society (Grant No. R73-A4284-13-S17). The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

Author information

Authors and Affiliations

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

    Anne Gulbech Ording, Uffe Heide-Jørgensen, Christian Fynbo Christiansen, Mette Nørgaard & Henrik Toft Sørensen

  2. Department of Clinical Epidemiology, Aarhus University, Aarhus N, Denmark

    John Acquavella

Authors
  1. Anne Gulbech Ording
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Uffe Heide-Jørgensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian Fynbo Christiansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mette Nørgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John Acquavella
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Henrik Toft Sørensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Henrik Toft Sørensen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ording, A.G., Heide-Jørgensen, U., Christiansen, C.F. et al. Site of metastasis and breast cancer mortality: a Danish nationwide registry-based cohort study. Clin Exp Metastasis 34, 93–101 (2017). https://doi.org/10.1007/s10585-016-9824-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-016-9824-8

Keywords

Search

Navigation