Breast Cancer Research and Treatment

, Volume 136, Issue 3, pp 795–804 | Cite as

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

  • L. Malorni
  • P. B. Shetty
  • C. De AngelisEmail author
  • S. Hilsenbeck
  • M. F. Rimawi
  • R. Elledge
  • C. K. Osborne
  • S. De Placido
  • G. Arpino
Clinical trial


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.


Basal-like breast cancer EGFR Estrogen receptor HER2 Progesterone receptor Triple-negative breast cancer 



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.


  1. 1.
    Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752PubMedCrossRefGoogle Scholar
  2. 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 100:10393–10398PubMedCrossRefGoogle Scholar
  3. 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 98:10869–10874PubMedCrossRefGoogle Scholar
  4. 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 100:8418–8423PubMedCrossRefGoogle Scholar
  5. 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 129:725–736PubMedCrossRefGoogle Scholar
  6. 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):405CrossRefGoogle Scholar
  7. 7.
    Bertucci F, Finetti P, Cervera N et al (2008) How basal are triple-negative breast cancers? Int J Cancer 123:236–240PubMedCrossRefGoogle Scholar
  8. 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 14:1368–1376PubMedCrossRefGoogle Scholar
  9. 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–S83Google Scholar
  10. 10.
    McGuire WL et al (1977) Evaluation of estrogen receptor assays in human breast cancer tissue. Cancer Res 37:637–639PubMedGoogle Scholar
  11. 11.
    Powell B et al (1979) Measurement of progesterone receptor in human breast cancer biopsies. Cancer Res 39:1678–1682PubMedGoogle Scholar
  12. 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 12:132Google Scholar
  13. 13.
    Dressler LG, Seamer LC, Owens MA et al (1988) DNA flow-cytometry and prognostic factors in 1331 frozen breast-cancer specimens. Cancer 61:420–427PubMedCrossRefGoogle Scholar
  14. 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 10:428–432PubMedGoogle Scholar
  15. 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 320:627–633PubMedCrossRefGoogle Scholar
  16. 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 28:9–20PubMedCrossRefGoogle Scholar
  17. 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 84:1279–1282PubMedCrossRefGoogle Scholar
  18. 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. 19.
    Curigliano G, Goldhirsch A (2011) The triple-negative subtype: new ideas for the poorest prognosis breast cancer. J Natl Cancer Inst Monogr 43:108–110CrossRefGoogle Scholar
  20. 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 97:1254–1261PubMedCrossRefGoogle Scholar
  21. 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 117:1575–1582PubMedCrossRefGoogle Scholar
  22. 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 27:3262Google Scholar
  23. 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. 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 17:818–826PubMedCrossRefGoogle Scholar
  25. 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): 9613Google Scholar
  26. 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 95:1825–1833PubMedCrossRefGoogle Scholar
  27. 27.
    Nicholson RI, Gee JM, Harper ME (2001) EGFR and cancer prognosis. Eur J Cancer 37(Suppl 4):S9–S15PubMedCrossRefGoogle Scholar
  28. 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 14:7861–7870PubMedCrossRefGoogle Scholar
  29. 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): 513Google Scholar
  30. 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 116:1234–1242PubMedCrossRefGoogle Scholar
  31. 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):S32Google Scholar
  32. 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 116:317–328PubMedCrossRefGoogle Scholar
  33. 33.
    Kolodner RD, Cleveland DW, Putnam CD (2011) Aneuploidy drives a mutator phenotype in cancer. Science 333:942–943PubMedCrossRefGoogle Scholar
  34. 34.
    Irshad S, Ellis P, Tutt A (2011) Molecular heterogeneity of triple-negative breast cancer and its clinical implications. Curr Opin Oncol 23:566–577PubMedCrossRefGoogle Scholar
  35. 35.
    Banerjee S, Reis JS, Ashley S et al (2006) Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J Clin Pathol 59:729–735PubMedCrossRefGoogle Scholar
  36. 36.
    Dent R, Trudeau M, Pritchard KI et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13:4429–4434PubMedCrossRefGoogle Scholar
  37. 37.
    Dent R, Trudeau M, Pritchard K et al (2007) Patterns of recurrence and prognosis in women with basal-like breast cancer. Breast 16:S25Google Scholar
  38. 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. 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):R65PubMedCrossRefGoogle Scholar
  40. 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 52:227–237PubMedCrossRefGoogle Scholar
  41. 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 28:92–98PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • L. Malorni
    • 1
    • 4
  • P. B. Shetty
    • 1
    • 2
  • C. De Angelis
    • 3
    Email author
  • S. Hilsenbeck
    • 1
    • 2
  • M. F. Rimawi
    • 1
    • 2
  • R. Elledge
    • 1
    • 2
  • C. K. Osborne
    • 1
    • 2
  • S. De Placido
    • 3
  • G. Arpino
    • 3
  1. 1.Lester and Sue Smith Breast Center at Baylor College of MedicineHoustonUSA
  2. 2.Dun L. Duncan Cancer Center at Baylor College of MedicineHoustonUSA
  3. 3.Department of Molecular and Clinical Endocrinology and OncologyUniversity of Naples Federico IINaplesItaly
  4. 4.“Sandro Pitigliani” Oncology UnitHospital of PratoPratoItaly

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