Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers

  • Sharon Nofech-Mozes
  • Maureen Trudeau
  • Harriet K. Kahn
  • Rebecca Dent
  • Ellen Rawlinson
  • Ping Sun
  • Steven A. Narod
  • Wedad M. Hanna
Epidemiology

Abstract

Traditional prognostic markers for breast cancer include estrogen receptor (ER), progesterone receptor (ER) and HER2/neu. Negative staining for these three markers defines the ‘triple-negative’ phenotype. By adding markers for cytokeratin 5/6 and EGFR, triple-negative breast cancers can be divided into ‘basal-like’ and ‘normal-like’ subgroups. We conducted immuno-staining on a panel of 958 patients with breast cancer, using all five markers and we followed the patients for distal recurrence and death. We compared rates of distal recurrence in the basal-like and normal-like subgroups with that of women with ER-positive breast cancer. Only 16 of 958 women had normal-like breast cancers. These cancers resembled basal-like cancers in that they had a high proliferative index, but the women with normal-like breast cancers resembled ER-positive women in terms of distant recurrence. The addition of CK5/6 and EGFR to the standard panel (ER/PR/HER2/neu) defines a small subgroup of women with normal-like breast cancer. The prognosis of these women may be superior to that of basal-like breast cancers but firm conclusions cannot be made.

Keywords

Triple-negative Basal-like Normal-like Breast cancer Prognosis Metastases 

Abbreviations

ER

Estrogen receptor

PR

Progesterone receptor

Notes

Acknowledgments

We thank the Canadian Breast Cancer Foundation (Ontario Chapter) for support of the Henrietta Banting Database.

References

  1. 1.
    Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752. doi:10.1038/35021093 CrossRefPubMedGoogle Scholar
  2. 2.
    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(14):8418–8423. doi:10.1073/pnas.0932692100 CrossRefPubMedGoogle 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(19):10869–10874. doi:10.1073/pnas.191367098 CrossRefPubMedGoogle Scholar
  4. 4.
    van’ V, Dai H, Van d V et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536. doi:10.1038/415530a CrossRefGoogle Scholar
  5. 5.
    Van d V, He YD, van’t Veer LJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347(25):1999–2009. doi:10.1056/NEJMoa021967 CrossRefGoogle Scholar
  6. 6.
    Fadare O, Tavassoli FA (2007) The phenotypic spectrum of basal-like breast cancers: a critical appraisal. Adv Anat Pathol 14(5):358–373. doi:10.1097/PAP.0b013e31814b26fe CrossRefPubMedGoogle Scholar
  7. 7.
    Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10(16):5367–5374. doi:10.1158/1078-0432.CCR-04-0220 CrossRefPubMedGoogle Scholar
  8. 8.
    Goldhirsch A, Wood WC, Gelber RD et al (2007) Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer. Ann Oncol 18(7):1133–1144. doi:10.1093/annonc/mdm271 CrossRefPubMedGoogle Scholar
  9. 9.
    Domagala W, Lasota J, Dukowicz A et al (1990) Vimentin expression appears to be associated with poor prognosis in node negative ductal NOS breast carcinomas. Am J Pathol 137:1299–1304PubMedGoogle Scholar
  10. 10.
    Li H, Cherukuri P, Li N, Cowling V et al (2007) Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors. Cancer Res 67(2):501–510. doi:10.1158/0008-5472.CAN-05-4571 CrossRefPubMedGoogle Scholar
  11. 11.
    Rakha EA, Putti TC, bd El-Rehim DM et al (2006) Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol 208(4):495–506. doi:10.1002/path.1916 CrossRefPubMedGoogle Scholar
  12. 12.
    Hoadley KA, Weigman VJ, Fan C et al (2007) EGFR associated expression profiles vary with breast tumor subtype. BMC Genomics 8:258. doi:10.1186/1471-2164-8-258 CrossRefPubMedGoogle Scholar
  13. 13.
    van de RM, Perou CM, Tibshirani R et al (2002) Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 161(6):1991–1996Google Scholar
  14. 14.
    Rakha EA, El-Rehim DA, Paish C et al (2006) Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer 42(18):3149–3156. doi:10.1016/j.ejca.2006.08.015 CrossRefPubMedGoogle Scholar
  15. 15.
    Dent R, Trudeau M, Pritchard KI et al (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13((15 Pt 1)):4429–4434. doi:10.1158/1078-0432.CCR-06-3045 CrossRefPubMedGoogle Scholar
  16. 16.
    Gaedcke J, Traub F, Milde S et al (2007) Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer. Mod Pathol 20(8):864–870. doi:10.1038/modpathol.3800830 CrossRefPubMedGoogle Scholar
  17. 17.
    Palmieri D, Smith QR, Lockman PR et al (2006) Brain metastases of breast cancer. Breast Dis 26:139–147PubMedGoogle Scholar
  18. 18.
    Dent R, Hanna WM, Ttrudeau M, et al. (2008) Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat (in press)Google Scholar
  19. 19.
    Livasy CA, Karaca G, Nanda R et al (2006) Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 19(2):264–271. doi:10.1038/modpathol.3800528 CrossRefPubMedGoogle Scholar
  20. 20.
    Rouzier R, Perou CM, Symmans WF et al (2005) Breast cancer molecular subtypes respond differently to pre-operative chemotherapy. Clin Cancer Res 11:5678–5685CrossRefPubMedGoogle Scholar
  21. 21.
    Jumppanen M, Gruvberger-Saal S, Kauraniemi P et al (2007) Basal-like phenotype is not associated with patient survival in estrogen-receptor-negative breast cancers. Breast Cancer Res 9(1):R16. doi:10.1186/bcr1649 CrossRefPubMedGoogle Scholar
  22. 22.
    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):R65CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Sharon Nofech-Mozes
    • 1
  • Maureen Trudeau
    • 2
  • Harriet K. Kahn
    • 1
  • Rebecca Dent
    • 2
  • Ellen Rawlinson
    • 3
  • Ping Sun
    • 3
  • Steven A. Narod
    • 3
  • Wedad M. Hanna
    • 1
  1. 1.Department of PathologySunnybrook Health Sciences Center and University of TorontoTorontoCanada
  2. 2.Department of Medical Oncology, Odette Cancer CentreSunnybrook Health Sciences Center and University of TorontoTorontoCanada
  3. 3.Women’s College Research InstituteWomen’s College Hospital and University of TorontoTorontoCanada

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