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BRCA1 dysfunction in sporadic basal-like breast cancer

Oncogene volume 26, pages 2126–2132 (2007)Cite this article

Abstract

Basal-like breast cancers form a distinct subtype of breast cancer characterized by the expression of markers expressed in normal basal/myoepithelial cells. Breast cancers arising in carriers of germline BRCA1 mutations are predominately of basal-like type, suggesting that BRCA1 dysfunction may play a role in the pathogenesis of sporadic basal-like cancers. We analysed 37 sporadic breast cancers expressing the basal marker cytokeratin 5/6, and age- and grade-matched controls, for downregulation of BRCA1. Although BRCA1 promoter methylation was no more common in basal-like cancers (basal 14% vs controls 11%, P=0.72), BRCA1 messenger RNA expression was twofold lower in basal-like breast cancers compared to matched controls (P=0.008). ID4, a negative regulator of BRCA1, was expressed at 9.1-fold higher levels in basal-like breast cancer (P<0.0001), suggesting a potential mechanism of BRCA1 downregulation. BRCA1 downregulation correlated with the presence of multiple basal markers, revealing heterogeneity in the basal-like phenotype. Finally, we found that 63% of metaplastic breast cancers, a rare type of basal-like cancers, had BRCA1 methylation, in comparison to 12% of controls (P<0.0001). The high prevalence of BRCA1 dysfunction identified in this study could be exploited in the development of novel approaches to targeted treatment of basal-like breast cancer.

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Acknowledgements

We thank Corrado D'Arrigo for useful discussions, and Louise Jones and Kellie Mulligan of St Bartholomew's Hospital, UK for Ck14 data from the Guy's Hospital Tissue Microarray.

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Authors and Affiliations

  1. Chester Beatty Laboratories, The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK

    N C Turner, J S Reis-Filho, A M Russell, D Steele, K Savage, A Ashworth & A N Tutt

  2. Medical Faculty and IPATIMUP Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

    J S Reis-Filho & F C Schmitt

  3. Breast Pathology Laboratory, Guy's Hospital, London, UK

    R J Springall, K Ryder, C E Gillett & A N Tutt

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  1. N C Turner
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  2. J S Reis-Filho
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  3. A M Russell
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  5. K Ryder
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  6. D Steele
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  7. K Savage
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  10. A Ashworth
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  11. A N Tutt
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Correspondence to A N Tutt.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Turner, N., Reis-Filho, J., Russell, A. et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene 26, 2126–2132 (2007). https://doi.org/10.1038/sj.onc.1210014

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