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Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients

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Abstract

Background

We analysed the clinical features, distribution of basal markers, prevalence of oncogene amplification, and outcome of triple negative (TN) compared to those of non-TN cancers in a series of adjuvant-anthracycline treated breast cancer patients.

Methods

We examined the prognostic impact of the TN and BL phenotype in 245 breast cancer patients uniformly treated with adjuvant anthracycline-based chemotherapy following primary surgery, with regards to local relapse-free (LRFS), metastasis free (MFS), and breast cancer specific survival (BCSS). A comparative analysis of the clinicopathological characteristics, expression of basal markers (cytokeratins (Cks) 5/6, 14, 17, EGFR, and caveolin 1 and 2), MIB-1, p53 and topoisomerase II alpha, and prevalence of CCND1, MYC and TOP2A amplification in TN and non-TN breast tumours was performed.

Results

TN cancers were significantly associated with the expression of basal markers (all P < 0.0001). However 19.4% of TN tumours were negative for basal markers, whilst 7.3% of non-TN tumours expressed basal markers. TN phenotype was significantly associated with p53, MIB-1 and topoisomerase II alpha (all, P < 0.01) expression. No TN cancer harboured amplification of CCND1 or TOP2A. In univariate analysis, TN and BL phenotype were significantly associated with shorter MFS (both, P < 0.01) and BCSS (both, P < 0.005) but not LRFS.

Conclusions

Despite treatment with standard dose anthracycline-based chemotherapy, the clinical outcome of TN and BL cancers remains poor. Alternative chemotherapeutic regimens and/or novel therapeutic approaches are warranted. Although a significant phenotypic overlap exists between TN and basal-like tumours, the TN phenotype is not an ideal surrogate marker for basal-like breast cancers.

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Acknowledgements

The authors are grateful to Professor Alan Ashworth for his insightful comments. This study was funded by Breakthrough Breast Cancer. Caterina Marchio is funded in part by the University of Turin and by Associazione Italiana per la Ricerca sul Cancro (AIRC, Milan, Regional Grant 1182).

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Authors and Affiliations

  1. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

    David S. P. Tan, Caterina Marchió, Kay Savage, Mitch Dowsett & Jorge S. Reis-Filho

  2. Breast Unit, The Royal Marsden Hospital Trust and Institute of Cancer Research London, London, SW3 6JJ, UK

    Robin L. Jones, Ian E. Smith & Mitch Dowsett

  3. Department of Academic Biochemistry, The Royal Marsden Hospital Trust, London, SW3 6JJ, UK

    Robin L. Jones & Mitch Dowsett

Authors
  1. David S. P. Tan
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  2. Caterina Marchió
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  3. Robin L. Jones
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  4. Kay Savage
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  5. Ian E. Smith
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  6. Mitch Dowsett
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  7. Jorge S. Reis-Filho
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Correspondence to Jorge S. Reis-Filho.

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Tan, D.S.P., Marchió, C., Jones, R.L. et al. Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients. Breast Cancer Res Treat 111, 27–44 (2008). https://doi.org/10.1007/s10549-007-9756-8

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