BRCA1 functions as a breast stem cell regulator
- Correspondence to: Professor W D Foulkes Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Room L10-116 Montreal General Hospital, 1650 Cedar Ave, Montreal, QC, Canada H3G 1A4; william.foulkesmcgill.ca
- Received 26 August 2003
- Accepted 22 September 2003
Abstract
BRCA1 is an important susceptibility gene for breast cancer, which confers substantial lifetime risks of breast cancer, particularly in the pre-menopausal age group. Typically, carriers of BRCA1 mutations develop breast tumours that grow rapidly and are high grade and oestrogen receptor negative. They also possess a basal epithelial phenotype, as defined by cytokeratin expression, that is not present in most breast cancers. It has recently been proposed that the adult breast stem cell expresses only basal keratins. Others have indicated a CD44 positive, CD24 negative phenotype for breast cancer stem cells. In this paper, I argue that the biology of human BRCA1 and its rodent homologues and the clinicopathological features of breast cancer related to BRCA1 support the notion that one of the key functions of BRCA1 is to act as a stem cell regulator. This has implications for the management of carriers of mutations of BRCA1, in part because support for the role of BRCA1 as a stem cell regulator would emphasise the distinct nature of breast cancer related to BRCA1.
