Skip to main content

Advertisement

SpringerLink
Log in

Impact of breast cancer subtypes and patterns of metastasis on outcome

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Clinical outcome of patients with stage IV breast cancer is dependent on tumor biology, extent, and localization of metastases. Routine imaging diagnostics for distant metastasis is not recommended by the national guidelines for breast cancer follow-up. In this study, we evaluated different patterns of metastases of cancer subtypes in order to generate hypotheses on individualization of follow-up after breast cancer in the adjuvant setting. Patients of the Regional Breast Cancer Center Dresden diagnosed within the years 2006–2011 were classified into the five intrinsic subtypes luminal A (ER+, Her2−, G1/2), luminal B/Her2 negative (ER+, Her2−, G3), triple positive (ER+, PR+, Her2+), Her2-enriched (ER−, Her2+), and triple negative (ER−, PR−, Her2−) and with a median follow-up of 45 months. Tumor stage at time of first diagnosis of breast cancer as well as time and site of metastasis at first diagnosis of distant metastatic disease was analyzed. Tumor specimen of 2284 female patients with primary breast cancer was classified into five subtypes. Distant recurrence-free survival at 3 years was most unfavorable in Her2-enriched (66.8 %), triple negative (75.9 %), and triple-positive breast cancer (81.7 %). The same subtypes most frequently presented with visceral metastases only at first presentation: Her2-enriched 46.9 %, triple negative 45.5 %, and triple-positive breast cancer 37.5 %. Longest median survival of 2.3 years was seen in luminal A and in Her2-enriched metastatic disease, respectively. Median survival was significantly better in the luminal A, Her2-enriched, and triple-positive subtype compared to triple-negative breast cancer (p < 0.005). Differences in time to metastatic disease, first localization of metastases, and overall survival after diagnosis of metastatic disease were shown. Considering new targeted therapies and the option of surgery of oligometastases, screening for visceral metastases might be reasonable after diagnosis of Her2-positive subtypes.

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
Fig. 3

Similar content being viewed by others

References

  1. Sant M, Allemani C, Berrino F, Coleman MP, Aareleid T, Chaplain G, Coebergh JW, Colonna M, Crosignani P, Danzon A et al (2004) Breast carcinoma survival in Europe and the United States. Cancer 100(4):715–722

    Article  PubMed  Google Scholar 

  2. Thomssen C, Diel I, Gnant M, Goldmann-Posch U, Goschke C, Haidinger R, Janni W, Lin NU (2012) Follow-up after breast cancer diagnosis. Breast Care (Basel, Switzerland) 8(6):457–460

    Google Scholar 

  3. Andre F, Slimane K, Bachelot T, Dunant A, Namer M, Barrelier A, Kabbaj O, Spano JP, Marsiglia H, Rouzier R et al (2004) Breast cancer with synchronous metastases: trends in survival during a 14-year period. J Clin Oncol 22(16):3302–3308

    Article  PubMed  Google Scholar 

  4. Adam R, Aloia T, Krissat J, Bralet MP, Paule B, Giacchetti S, Delvart V, Azoulay D, Bismuth H, Castaing D (2006) Is liver resection justified for patients with hepatic metastases from breast cancer? Ann Surg 244(6):897–907 discussion 907-898

    Article  PubMed Central  PubMed  Google Scholar 

  5. Clark GM, Sledge GW Jr, Osborne CK, McGuire WL (1987) Survival from first recurrence: relative importance of prognostic factors in 1015 breast cancer patients. J Clin Oncol 5(1):55–61

    CAS  PubMed  Google Scholar 

  6. Falkson G, Gelman R, Falkson CI, Glick J, Harris J (1991) Factors predicting for response, time to treatment failure, and survival in women with metastatic breast cancer treated with DAVTH: a prospective Eastern Cooperative Oncology Group study. J Clin Oncol 9(12):2153–2161

    CAS  PubMed  Google Scholar 

  7. Vogel CL, Azevedo S, Hilsenbeck S, East DR, Ayub J (1992) Survival after first recurrence of breast cancer. The Miami experience. Cancer 70(1):129–135

    Article  CAS  PubMed  Google Scholar 

  8. Largillier R, Ferrero JM, Doyen J, Barriere J, Namer M, Mari V, Courdi A, Hannoun-Levi JM, Ettore F, Birtwisle-Peyrottes I et al (2008) Prognostic factors in 1038 women with metastatic breast cancer. Ann Oncol: Off J Eur Soc Med Oncol/ESMO 19(12):2012–2019

    Article  CAS  Google Scholar 

  9. Rudat V, El-Sweilmeen H, Brune-Erber I, Nour AA, Almasri N, Altuwaijri S, Fadel E (2014) Identification of breast cancer patients with a high risk of developing brain metastases: a single-institutional retrospective analysis. BMC Cancer 14(1):289

    Article  PubMed Central  PubMed  Google Scholar 

  10. Vona-Davis L, Rose DP, Gadiyaram V, Ducatman B, Hobbs G, Hazard H, Kurian S, Abraham J (2014) Breast cancer pathology, receptor status, and patterns of metastasis in a rural appalachian population. J Cancer Epidemiol 2014:170634

    Article  PubMed Central  PubMed  Google Scholar 

  11. Pagani O, Price KN, Gelber RD, Castiglione-Gertsch M, Holmberg SB, Lindtner J, Thurlimann B, Collins J, Fey MF, Coates AS et al (2009) Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century. Breast Cancer Res Treat 117(2):319–324

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100(14):8418–8423

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ (2011) Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol: Off J Eur Soc Med Oncol/ESMO 22(8):1736–1747

    Article  CAS  Google Scholar 

  14. Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M et al (2015) The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 16(1):25–35

    Article  CAS  PubMed  Google Scholar 

  15. Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J et al (2014) Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32(19):2078–2099

    Article  CAS  PubMed  Google Scholar 

  16. von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30(15):1796–1804

    Article  Google Scholar 

  17. Carlson RW, Moench SJ, Hammond ME, Perez EA, Burstein HJ, Allred DC, Vogel CL, Goldstein LJ, Somlo G, Gradishar WJ et al (2006) HER2 testing in breast cancer: NCCN Task Force report and recommendations. J Nat Compr Cancer Netw 4(Suppl 3):S1–22 quiz S23-24

    Google Scholar 

  18. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752

    Article  CAS  PubMed  Google Scholar 

  19. Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JG, Foekens JA, Martens JW (2008) Subtypes of breast cancer show preferential site of relapse. Cancer Res 68(9):3108–3114

    Article  CAS  PubMed  Google Scholar 

  20. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH (2010) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28(1):92–98

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Ribelles N, Perez-Villa L, Jerez JM, Pajares B, Vicioso L, Jimenez B, de Luque V, Franco L, Gallego E, Marquez A et al (2013) Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index. Breast Cancer Res 15(5):R98

    Article  PubMed Central  PubMed  Google Scholar 

  22. Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26(8):1275–1281

    Article  PubMed  Google Scholar 

  23. Fiteni F, Villanueva C, Bazan F, Perrin S, Chaigneau L, Dobi E, Montcuquet P, Cals L, Meneveau N, Nerich V et al (2013) Long-term follow-up of patients with metastatic breast cancer treated by trastuzumab: impact of institutions. Breast (Edinburgh, Scotland) 23:165–169

    Article  Google Scholar 

  24. Santini D, Vincenzi B, Pantano F, Tonini G, Bertoldo F (2011) Targeting bone metastases starting from the preneoplastic niche: home sweet home. Breast Cancer Res 13(4):111

    Article  PubMed Central  PubMed  Google Scholar 

  25. Ignatiadis M, Dawson SJ (2014) Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality? Ann Oncol: Off J Eur Soc Med Oncol/ESMO 25:2304–2313

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Tumorzentrum e.V. Dresden.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Technische Universität Dresden, Dresden, Germany

    Karin Kast, Theresa Link, Andrea Petzold & Pauline Wimberger

  2. German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Karin Kast, Theresa Link, Katrin Friedrich, Andrea Petzold, Gustavo Baretton & Pauline Wimberger

  3. Institute of Pathology, Technische Universität Dresden, Dresden, Germany

    Katrin Friedrich & Gustavo Baretton

  4. Regional Clinical Cancer Registry, Technische Universität Dresden, Dresden, Germany

    Antje Niedostatek, Carmen Werner & Stefanie J. Klug

  5. Cancer Epidemiology, University Cancer Center, Technische Universität Dresden, Dresden, Germany

    Olaf Schoffer & Stefanie J. Klug

  6. Department of Gynecology and Obstetrics, Diakonissenkrankenhaus Dresden, Dresden, Germany

    Andreas Werner

  7. Department of Gynecology and Obstetrics, St. Joseph-Stift Dresden, Dresden, Germany

    Axel Gatzweiler

  8. Department of Gynecology and Obstetrics, Elblandkliniken Radebeul, Radebeul, Germany

    Barbara Richter

Authors
  1. Karin Kast
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katrin Friedrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Petzold
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antje Niedostatek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Olaf Schoffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carmen Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stefanie J. Klug
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andreas Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Axel Gatzweiler
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Barbara Richter
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gustavo Baretton
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pauline Wimberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karin Kast.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 75 kb)

Supplementary material 2 (DOCX 21 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kast, K., Link, T., Friedrich, K. et al. Impact of breast cancer subtypes and patterns of metastasis on outcome. Breast Cancer Res Treat 150, 621–629 (2015). https://doi.org/10.1007/s10549-015-3341-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-015-3341-3

Keywords

Search

Navigation