Skip to main content
SpringerLink
Log in

Hormone receptor, human epidermal growth factor receptor-2, and Ki-67 status in primary breast cancer and corresponding recurrences or synchronous axillary lymph node metastases

Surgery Today volume 50, pages 657–663 (2020)Cite this article

Abstract

The therapeutic strategy for breast cancer is determined by the surrogate subtype, which is defined by biomarkers, such as estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2), and Ki-67. In previous reports, the rate of discordance in ER, PgR, and HER2 between primary breast cancer and recurrent lesions or synchronous axillary lymph node metastasis was 15–25, 25–40, and 5–25 or 7–50, 10–50, and 3–30%, respectively. Overall, hormone receptors tended to weaken during the metastatic process, while patterns of HER2 were not uniform. Regarding the Ki-67 labeling index, an increase in metastatic lesions compared with primary lesions was the dominant pattern, suggesting that aggressive subclones with high proliferative potential form metastases. The loss of expression of hormone receptor or an increase in the Ki-67 labeling index in metastasis seemed to be associated with a poor prognosis. However, most previous studies did not report the background characteristics of patients, or they included subjects with varied characteristics, including those on systemic therapy, and were based on relatively small populations; therefore, definitive conclusions could not be drawn. Future studies should explore how to select therapies according to the biomarkers in primary breast cancer and/or its metastasis.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

References

  1. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.

    Article  CAS  Google Scholar 

  2. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.

    Article  CAS  Google Scholar 

  3. Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies-improving the management of early breast cancer: St gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;26:1533–46.

    Article  CAS  Google Scholar 

  4. National Comprehensive Cancer Network. Breast cancer (version 1.2019). 2019. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

  5. Liedtke C, Broglio K, Moulder S, Hsu L, Kau SW, Symmans WF, et al. Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol. 2009;20:1953–8.

    Article  CAS  Google Scholar 

  6. Nishimura R, Osako T, Okumura Y, Tashima R, Toyozumi Y, Arima N. Changes in the er, pgr, her2, p53 and ki-67 biological markers between primary and recurrent breast cancer: Discordance rates and prognosis. World J Surg Oncol. 2011;9:131.

    Article  Google Scholar 

  7. Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012;30:587–92.

    Article  Google Scholar 

  8. Jensen JD, Knoop A, Ewertz M, Laenkholm AV. ER, HER2, and top2a expression in primary tumor, synchronous axillary nodes, and asynchronous metastases in breast cancer. Breast Cancer Res Treat. 2012;132:511–21.

    Article  CAS  Google Scholar 

  9. Lindstrom LS, Karlsson E, Wilking UM, Johansson U, Hartman J, Lidbrink EK, et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol. 2012;30:2601–8.

    Article  Google Scholar 

  10. Niikura N, Liu J, Hayashi N, Mittendorf EA, Gong Y, Palla SL, et al. Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol. 2012;30:593–9.

    Article  Google Scholar 

  11. Ibrahim T, Farolfi A, Scarpi E, Mercatali L, Medri L, Ricci M, et al. Hormonal receptor, human epidermal growth factor receptor-2, and ki67 discordance between primary breast cancer and paired metastases: clinical impact. Oncology. 2013;84:150–7.

    Article  CAS  Google Scholar 

  12. Curtit E, Nerich V, Mansi L, Chaigneau L, Cals L, Villanueva C, et al. Discordances in estrogen receptor status, progesterone receptor status, and HER2 status between primary breast cancer and metastasis. Oncologist. 2013;18:667–74.

    Article  Google Scholar 

  13. Dieci MV, Barbieri E, Piacentini F, Ficarra G, Bettelli S, Dominici M, et al. Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single-institution analysis. Ann Oncol. 2013;24:101–8.

    Article  CAS  Google Scholar 

  14. Shin HC, Han W, Moon HG, Park IA, Noh DY, et al. Patients with concordant triple-negative phenotype between primary breast cancers and corresponding metastases have poor prognosis. J Breast Cancer. 2016;19:268–74.

    Article  Google Scholar 

  15. Meng X, Song S, Jiang ZF, Sun B, Wang T, Zhang S, et al. Receptor conversion in metastatic breast cancer: a prognosticator of survival. Oncotarget. 2016;7:71887–903.

    Article  Google Scholar 

  16. Richter S, Zandvakili A. Meta analysis of discordant HER2 status in matched primary and metastatic breast cancer. Cancer Res. 2011;71(24):05.

    Google Scholar 

  17. Lower EE, Glass EL, Bradley DA, Blau R, Heffelfinger S. Impact of metastatic estrogen receptor and progesterone receptor status on survival. Breast Cancer Res Treat. 2005;90:65–70.

    Article  CAS  Google Scholar 

  18. Wilking U, Karlsson E, Skoog L, Hatschek T, Lidbrink E, Elmberger G, et al. HER2 status in a population-derived breast cancer cohort: discordances during tumor progression. Breast Cancer Res Treat. 2011;125:553–61.

    Article  CAS  Google Scholar 

  19. Falck AK, Ferno M, Bendahl PO, Ryden L. Does analysis of biomarkers in tumor cells in lymph node metastases give additional prognostic information in primary breast cancer? World J Surg. 2010;34:1434–41.

    Article  Google Scholar 

  20. Torres L, Ribeiro FR, Pandis N, Andersen JA, Heim S, Teixeira MR. Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases. Breast Cancer Res Treat. 2007;102:143–55.

    Article  Google Scholar 

  21. Brunelli M, Manfrin E, Martignoni G, Miller K, Remo A, Reghellin D, et al. Genotypic intratumoral heterogeneity in breast carcinoma with HER2/neu amplification: Evaluation according toASCO/CAP criteria. Am J Clin Pathol. 2009;131:678–82.

    Article  Google Scholar 

  22. Shah SP, Morin RD, Khattra J, Prentice L, Pugh T, Burleigh A, et al. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature. 2009;461:809–13.

    Article  CAS  Google Scholar 

  23. Mann GB, Fahey VD, Feleppa F, Buchanan MR. Reliance on hormone receptor assays of surgical specimens may compromise outcome in patients with breast cancer. J Clin Oncol. 2005;23:5148–54.

    Article  Google Scholar 

  24. Kulka J, Szekely B, Lukacs LV, Kiss O, Tokes AM, Vincze E, et al. Comparison of predictive immunohistochemical marker expression of primary breast cancer and paired distant metastasis using surgical material: a practice-based study. J Histochem Cytochem. 2016;64:256–67.

    Article  CAS  Google Scholar 

  25. Zhao S, Xu L, Liu W, Lv C, Zhang K, Gao H, et al. Comparison of the expression of prognostic biomarkers between primary tumor and axillary lymph node metastases in breast cancer. Int J Clin Exp Pathol. 2015;8:5744–8.

    PubMed  PubMed Central  Google Scholar 

  26. Ba JL, Liu CG, Jin F. Alterations in hormonal receptor expression and HER2 status between primary breast tumors and paired nodal metastases: discordance rates and prognosis. Asian Pac J Cancer Prev. 2014;15:9233–9.

    Article  Google Scholar 

  27. El Nemr Esmail RS, El Farouk Abdel-Salam LO, Abd El Ellah MM. Could the breast prognostic biomarker status change during disease progression? An immunohistochemical comparison between primary tumors and synchronous nodal metastasis. Asian Pac J Cancer Prev. 2015; 16:4317–21.

  28. Kinoe H, Yamanouchi K, Kuba S, Morita M, Sakimura C, Kanetaka K, et al. Discordance in hormone receptor, human epidermal growth factor receptor-2, and ki-67 between primary breast cancer and synchronous axillary lymph node metastasis. JBUON. 2018;23:S60–S6666.

    Google Scholar 

  29. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.

    Article  Google Scholar 

  30. Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Murphy GP. Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer. 1980;45:2917–24.

    Article  CAS  Google Scholar 

  31. Jatoi I, Hilsenbeck SG, Clark GM, Osborne CK. Significance of axillary lymph node metastasis in primary breast cancer. J Clin Oncol. 1999;17:2334–400.

    Article  CAS  Google Scholar 

  32. Mando P, Rizzo M, de la Puente CP, Maino M, Ponce C, Pombo MT, et al. High histologic grade and high ki-67 expression predict phenotypic alterations in node metastasis in primary breast cancers. J Breast Cancer. 2017;20:170–5.

    Article  Google Scholar 

  33. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody ki-67. J Immunol. 1984;133:1710–5.

    CAS  PubMed  Google Scholar 

  34. Park D, Karesen R, Noren T, Sauer T. Ki-67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications. Virchows Arch. 2007;451:11–8.

    Article  CAS  Google Scholar 

  35. Tawfik K, Kimler BF, Davis MK, Fan F, Tawfik O. Ki-67 expression in axillary lymph node metastases in breast cancer is prognostically significant. Hum Pathol. 2013;44:39–46.

    Article  CAS  Google Scholar 

  36. de Azambuja E, Cardoso F, de Castro G Jr, Colozza M, Mano MS, Durbecq V, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96:1504–13.

    Article  Google Scholar 

  37. Stuart-Harris R, Caldas C, Pinder SE, Pharoah P. Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast. 2008;17:323–34.

    Article  CAS  Google Scholar 

  38. Dowsett M, Dunbier AK. Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res. 2008;14:8019–26.

    Article  CAS  Google Scholar 

  39. Nishimura R, Osako T, Okumura Y, Hayashi M, Arima N. Clinical significance of ki-67 in neoadjuvant chemotherapy for primary breast cancer as a predictor for chemosensitivity and for prognosis. Breast Cancer. 2010;17:269–75.

    Article  Google Scholar 

  40. Tanei T, Shimomura A, Shimazu K, Nakayama T, Kim SJ, Iwamoto T, et al. Prognostic significance of ki67 index after neoadjuvant chemotherapy in breast cancer. Eur J Surg Oncol. 2011;37:155–61.

    Article  CAS  Google Scholar 

  41. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the st gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24:2206–23.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Kosho Yamanouchi, Sayaka Kuba & Susumu Eguchi

Authors
  1. Kosho Yamanouchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sayaka Kuba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susumu Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kosho Yamanouchi.

Ethics declarations

Conflict of interest

Kosho Yamanouchi, Sayaka Kuba, and Susumu Eguchi have no conflicts of interest to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamanouchi, K., Kuba, S. & Eguchi, S. Hormone receptor, human epidermal growth factor receptor-2, and Ki-67 status in primary breast cancer and corresponding recurrences or synchronous axillary lymph node metastases. Surg Today 50, 657–663 (2020). https://doi.org/10.1007/s00595-019-01831-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-019-01831-8

Keywords

search

Navigation