Skip to main content

Advertisement

SpringerLink
Log in

Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up

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

Abstract

Studies on well characterized, large populations of estrogen receptor (ER)/progesterone receptor (PgR)/HER2-negative [triple-negative (TN)] breast cancer (BC) patients with long-term follow-up are lacking. In this study, we analyze clinical outcomes of TN BC and implications of epidermal growth factor receptor (EGFR) expression. Clinical and biologic features, time to first recurrence (TTFR), and overall survival (OS) were compared in 253 TN versus 1,036 ER positive, PgR positive, HER2-negative [estrogen-driven (ED)] BC. Compared to ED, TN tumors were larger (p = 0.02), more proliferative (high S-phase 54 vs. 17 %, p < 0.0001), more aneuploid (64 vs. 43 %, p < 0.0001) and more likely EGFR positive (≥10 fmol/mg by radioligand-binding assay, 49 vs. 7 %, p < 0.0001). Among TN, EGFR-positive BC were larger (p = 0.0018), more proliferative (p < 0.0001), and more aneuploid, (p < 0.0001) than EGFR-negative BC. Adjuvant-treated TN patients had shorter TTFR (p = 0.0003), and OS (p = 0.0017), than ED patients. However, in untreated patients, no differences in TTFR and OS were observed at 8 years median follow-up. Among TN patients, EGFR expression was not associated with worse outcome. TN tumors have a worse outcome in systemically treated patients but not in untreated patients. EGFR expression, does not predict for worse long-term survival.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  PubMed  CAS  Google Scholar 

  2. Sotiriou C, Neo SY, McShane LM et al (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA 100:10393–10398

    Article  PubMed  CAS  Google Scholar 

  3. Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874

    Article  PubMed  CAS  Google Scholar 

  4. Sorlie T, Tibshirani R, Parker J et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423

    Article  PubMed  CAS  Google Scholar 

  5. Hartog H, Horlings HM, van der Vegt B et al (2011) Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma. Breast Cancer Res Treat 129:725–736

    Article  PubMed  CAS  Google Scholar 

  6. Kreike B, van de Vijver MJ (2007) Are triple-negative tumours and basal-like breast cancer synonymous? Authors’ response. Breast Cancer Res 9(6):405

    Article  Google Scholar 

  7. Bertucci F, Finetti P, Cervera N et al (2008) How basal are triple-negative breast cancers? Int J Cancer 123:236–240

    Article  PubMed  CAS  Google Scholar 

  8. Cheang MCU, Voduc D, Bajdik C et al (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value then triple-negative phenotype. Clin Cancer Res 14:1368–1376

    Article  PubMed  CAS  Google Scholar 

  9. Dent R, Trudeau M, Sun P, Narod S (2007) Patterns of metastatic spread in triple negative breast cancer. Breast Cancer Res Treat 106:S41–S83

    Google Scholar 

  10. McGuire WL et al (1977) Evaluation of estrogen receptor assays in human breast cancer tissue. Cancer Res 37:637–639

    PubMed  CAS  Google Scholar 

  11. Powell B et al (1979) Measurement of progesterone receptor in human breast cancer biopsies. Cancer Res 39:1678–1682

    PubMed  CAS  Google Scholar 

  12. Clark GM, Dressler LG, Owens MA, Mcguire WL (1988) Flow-cytometry identifies a group of node-negative breast-cancer patients with low-risk of recurrence. Breast Cancer Res Treat 12:132

    Google Scholar 

  13. Dressler LG, Seamer LC, Owens MA et al (1988) DNA flow-cytometry and prognostic factors in 1331 frozen breast-cancer specimens. Cancer 61:420–427

    Article  PubMed  CAS  Google Scholar 

  14. Clark GM, Mathieu MC, Owens MA et al (1992) Prognostic-significance of s-phase fraction in good-risk, node-negative breast-cancer patients. J Clin Oncol 10:428–432

    PubMed  CAS  Google Scholar 

  15. Clark GM, Dressler LG, Owens MA et al (1989) Prediction of relapse or survival in patients with node-negative breast-cancer by DNA flow-cytometry. N Engl J Med 320:627–633

    Article  PubMed  CAS  Google Scholar 

  16. Wenger CR, Beardslee S, Owens MA et al (1993) DNA-ploidy, S-phase, and steroid-receptors in more than 127, 000 breast-cancer patients. Breast Cancer Res Treat 28:9–20

    Article  PubMed  CAS  Google Scholar 

  17. Ciocca DR, Fujimura FK, Tandon AK et al (1992) Correlation of Her-2/Neu amplification with expression and with other prognostic factors in 1103 breast cancers. J Natl Cancer Inst 84:1279–1282

    Article  PubMed  CAS  Google Scholar 

  18. Klijn JGM, Berns PMJJ, Bontenbal M, Foekens JA (2006) Growth-factors: clinical implications in breast-cancer. Breast Cancer: from Biology to Therapy. doi:10.1111/j.1749-6632.1993.tb17193.x

  19. Curigliano G, Goldhirsch A (2011) The triple-negative subtype: new ideas for the poorest prognosis breast cancer. J Natl Cancer Inst Monogr 43:108–110

    Article  CAS  Google Scholar 

  20. Arpino G, Weiss H, Lee AV et al (2005) Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst 97:1254–1261

    Article  PubMed  CAS  Google Scholar 

  21. Kaufmann M, Pusztai L (2011) Use of standard markers and incorporation of molecular markers into breast cancer therapy consensus recommendations from an international expert panel. Cancer 117:1575–1582

    Article  PubMed  Google Scholar 

  22. Huo DZ, Senie RT, Daly M et al (2009) Prediction of BRCA mutations using the BRCAPRO model in clinic-based African American, Hispanic, and other minority families in the United States (vol 27, p 1184, 2009). J Clin Oncol 27:3262

  23. Stead LA, Lash TL, Sobieraj JE et al (2009) Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res 11:R18. doi:10.1186/bcr2242

  24. Dowsett M, Houghton J, Iden C et al (2006) Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol 17:818–826

    Article  PubMed  CAS  Google Scholar 

  25. Leitzel K, Souder C, Ali SM et al (2005) Serum EGFR/HER-2 combination predicts poor survival in metastatic breast cancer. (J Clin Oncol Meeting Abstracts) 23(16): 9613

    Google Scholar 

  26. Lu CH, Speers C, Zhang Y et al (2003) Effect of epidermal growth factor receptor inhibitor on development of estrogen receptor-negative mammary tumors. J Natl Cancer Inst 95:1825–1833

    Article  PubMed  CAS  Google Scholar 

  27. Nicholson RI, Gee JM, Harper ME (2001) EGFR and cancer prognosis. Eur J Cancer 37(Suppl 4):S9–S15

    Article  PubMed  CAS  Google Scholar 

  28. Press MF, Finn RS, Cameron D et al (2008) HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer. Clin Cancer Res 14:7861–7870

    Article  PubMed  CAS  Google Scholar 

  29. Rimawi MF, Weiss HL, Bhatia P et al (2006) EGFR expression in breast cancer: association with biologic phenotype, prognosis, and resistance to adjuvant therapy. J Clin Oncol (Meeting Abstracts) 24(18): 513

    Google Scholar 

  30. Rimawi MF, Shetty PB, Weiss HL et al (2010) Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes. Cancer 116:1234–1242

    Article  PubMed  Google Scholar 

  31. Carey L, Mayer E, Marcom P et al (2007) TBCRC 001: EGFR inhibition with cetuximab in metastatic triple negative (basal-like) breast cancer (abstract 307). Breast Cancer Res Treat 106(suppl 1):S32

    Google Scholar 

  32. Viale G, Rotmensz N, Maisonneuve P et al (2009) Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat 116:317–328

    Article  PubMed  CAS  Google Scholar 

  33. Kolodner RD, Cleveland DW, Putnam CD (2011) Aneuploidy drives a mutator phenotype in cancer. Science 333:942–943

    Article  PubMed  CAS  Google Scholar 

  34. Irshad S, Ellis P, Tutt A (2011) Molecular heterogeneity of triple-negative breast cancer and its clinical implications. Curr Opin Oncol 23:566–577

    Article  PubMed  CAS  Google Scholar 

  35. Banerjee S, Reis JS, Ashley S et al (2006) Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J Clin Pathol 59:729–735

    Article  PubMed  CAS  Google Scholar 

  36. Dent R, Trudeau M, Pritchard KI et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434

    Article  PubMed  Google Scholar 

  37. Dent R, Trudeau M, Pritchard K et al (2007) Patterns of recurrence and prognosis in women with basal-like breast cancer. Breast 16:S25

    Google Scholar 

  38. Kreike B, van de Vijver MJ (2007) Are triple-negative tumours and basal-like breast cancer synonymous? Breast Cancer Res 9(6): 405. doi:10.1186/bcr1832

  39. Kreike B, van Kouwenhove M, Horlings H et al (2007) Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 9(5):R65

    Article  PubMed  Google Scholar 

  40. Hilsenbeck SG, Ravdin PM, de Moor CA et al (1998) Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res Treat 52:227–237

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The Authors have no financial disclosures to declare. This study was funded in part by a NIH grant P50-CA58183 (SPORE) and a Susan Komen for the Cure Foundation Post-doctoral Fellowship Award.

Author information

Authors and Affiliations

  1. Lester and Sue Smith Breast Center at Baylor College of Medicine, Houston, TX, USA

    L. Malorni, P. B. Shetty, S. Hilsenbeck, M. F. Rimawi, R. Elledge & C. K. Osborne

  2. Dun L. Duncan Cancer Center at Baylor College of Medicine, Houston, TX, USA

    P. B. Shetty, S. Hilsenbeck, M. F. Rimawi, R. Elledge & C. K. Osborne

  3. Department of Molecular and Clinical Endocrinology and Oncology, University of Naples Federico II, Naples, Italy

    C. De Angelis, S. De Placido & G. Arpino

  4. “Sandro Pitigliani” Oncology Unit, Hospital of Prato, Prato, Italy

    L. Malorni

Authors
  1. L. Malorni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. B. Shetty
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. De Angelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Hilsenbeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. F. Rimawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Elledge
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. K. Osborne
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. De Placido
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. Arpino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. De Angelis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Malorni, L., Shetty, P.B., De Angelis, C. et al. Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up. Breast Cancer Res Treat 136, 795–804 (2012). https://doi.org/10.1007/s10549-012-2315-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-012-2315-y

Keywords

Search

Navigation