Basal tumours may originate from breast stem cells that have undergone genetic mishaps

Jul 24 2006

The most aggressive form of breast cancer may originate from breast stem cells that have undergone genetic mishaps.

Victorian Breast Cancer Research Consortium scientists from The Walter and Eliza Hall Institute, using mouse models, have discovered that breast stem cells do not express receptors for the female hormones oestrogen or progesterone. These and other features of the stem cell resemble the aggressive 'basal' subtype of breast cancer. There is increasing evidence that breast cancer is not simply a single disease. Scientists now view breast cancer as a heterogeneous disease, made up of various subtypes. This observation has led to speculation that breast tumours are derived from different cell types that could include the breast stem cell or its descendents that have suffered genetic accidents.

This possibility has generated great interest in understanding the composition of normal breast cells including the stem cell. A question of particular interest is whether the breast stem cell expresses receptors for oestrogen and progesterone and the marker 'Her2', since these help define the subtypes of breast cancer; and also guide current approaches to therapy.

The WEHI team, together with the Eaves group in Vancouver, have found that the breast stem cell in mice is 'triple negative' for oestrogen, progesterone and Her2 receptors but does express certain 'basal cell' markers. These characteristics also define the basal subtype of breast cancer, which is more commonly seen in tumours that develop in women who are carriers of the breast cancer predisposing gene BRCA1.

These findings support previous speculation that breast stem cells, or very early descendents, are the cells from which basal tumours arise. Dr Visvader, who led the team effort with Dr Lindeman at WEHI, said, "This finding made by Marie-Liesse Asselin-Labat in our lab reinforces the need to understand the normal biology of the breast stem cell. Our hope is that this kind of research could in the long-term lead to the identification of new therapeutic targets against breast cancer, particularly the basal subtype." Currently drugs such as Tamoxifen, the aromatase inhibitors or Herceptin are ineffective against basal tumours and chemotherapy is the only option.

Dr Lindeman, who is also an oncologist at the Royal Melbourne Hospital, said that their team's findings will now be extended using excised human breast tissue and tumours. "We are fortunate that the Royal Melbourne Hospital campus is strongly committed to this type of translational research. Our hope is that this will lead to better cancer outcomes from a disease that strikes one in 11 Australian women." The team findings are published in the Journal of the National Cancer Institute.