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BRACking news on triple-negative/basal-like breast cancers: how BRCA1 deficiency may result in the development of a selective tumor subtype

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Abstract

Mutations in the BRCA1 tumor suppressor predispose to the development of breast and ovarian cancers. Noticeably, the majority of BRCA1-associated breast cancers are triple-negative (ER-, PR- and HER2-) and display a basal-like phenotype, which are features relatively uncommon among sporadic breast cancers. It is well documented that BRCA1 is involved in a number of cellular functions converging to the maintenance of genomic stability. However, the control over DNA integrity does not seem to account for the peculiar phenotype of BRCA1-associated tumors since mutations in other genes involved in such a function, namely BRCA2, associate to a broader spectrum of breast carcinoma subtypes. Indeed, an increasing body of evidence indicates that BRCA1 is implicated also in the regulation of transcription by impinging upon general components of the transcriptional machinery. Thus, elucidating the complex biochemical network regulated by BRCA1 may allow a better understanding also of the biology of sporadic triple-negative/basal-like tumors and lay down the basis for novel preventive measures and more effective therapeutic strategies. This review summarizes recent findings on the role of BRCA1 in the regulation of transcription and how this might set the ground for the development of cancers with triple-negative/basal-like features.

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Acknowledgments

The authors acknowledge financial support from the Associazione Italiana per la Ricerca sul Cancro (AIRC), Regione Friuli Venezia Giulia, Italian Ministry of Health and Associazione Via di Natale.

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  1. Experimental Oncology 1, CRO IRCCS, National Cancer Institute, Aviano, PN, Italy

    Manuela Santarosa & Roberta Maestro

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Santarosa, M., Maestro, R. BRACking news on triple-negative/basal-like breast cancers: how BRCA1 deficiency may result in the development of a selective tumor subtype. Cancer Metastasis Rev 31, 131–142 (2012). https://doi.org/10.1007/s10555-011-9336-6

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