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Hormone sensitivity of breast stem cells presents drug target

Researchers at the Walter and Eliza Hall Institute have discovered that breast stem cells are exquisitely sensitive to the female hormones oestrogen and progesterone, a finding that opens the way for the development of new preventions and treatments for breast cancer.

The discovery, by scientists in the institute's Stem Cells and Cancer and Bioinformatics divisions, also explains decades of evidence linking breast cancer risk to exposure to female hormones.

It has been published online today in the international journal Nature.

Dr Jane Visvader, who led the research with Dr Geoff Lindeman, said sustained exposure to oestrogen and progesterone was a well-established risk factor for breast cancer. "There is a clear evidence that the more menstrual cycles a woman has the greater her breast cancer risk," Dr Visvader said. "There is even an increase in breast cancer risk in the short-term following pregnancy. However the cellular basis for these observations has been poorly understood."

In the mid-2000s, Drs Visvader and Lindeman discovered breast stem cells in both mice and humans. Unexpectedly, however, they also found that breast stem cells lacked 'receptors' that would allow them to be directly controlled by the female hormones oestrogen and progesterone.

Now, work by Drs Visvader and Lindeman in collaboration with Drs Marie-Liesse Asselin-Labat, Gordon Smyth and others at the institute, has revealed that despite lacking receptors for oestrogen and progesterone, breast stem cells are still remarkably sensitive to female hormones.

Using mouse models, they showed that when the ovaries were removed or the animals were treated with hormone inhibitors (which are in clinical use as anti-breast cancer agents), breast stem cell numbers dropped and the cells appeared to become dormant.

Dr Lindeman, who is also a medical oncologist at the Royal Melbourne Hospital, said this finding helped to expl

Contact: Penny Fannin
Walter and Eliza Hall Institute

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