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New research links ovarian hormones with breast stem-cell growth

Canadian researchers have discovered a link between ovarian hormones and breast stem-cell growth, a finding that appears to set the stage for the development of breast cancer.

The research, published in the journal Nature, adds to the body of knowledge of how breast cancer develops. Earlier studies have suggested a link between ovarian hormones and breast cancer, and there is mounting evidence that stem cells act as the seed for breast cancer.

With this study, researchers show that the hormone progesterone alters breast stem cells and how a woman's reproductive history is a risk factor for the disease taking root.

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"Stem cells in the adult females were thought to be inactive and constant in number. Now we make a very fundamental observation really showing that ovarian hormones during reproductive cycles alter breast stem-cell numbers," said principal investigator Rama Khokha, a molecular biologist at the Ontario Cancer Institute and the Campbell Family Cancer Research Institute at the Princess Margaret Hospital.

"This fundamental observation opens up new ways of thinking … into the mechanism that may underlie how hormones may be linking to that increased risk of breast cancer."

A growing body of research suggests that abnormal stem cells, which can multiply without limit, are the seed cells behind several kinds of malignancies – including cancers of the breast, brain, pancreas and ovaries.

Studies have also indicated that women who menstruate early and women who reach menopause later in life, and as a result have more reproductive cycles, are at increased risk for breast cancer. But it was not known how progesterone levels were involved in this risk – until now.

Dr. Khokha and her team found that when progesterone levels peak during the second half of the menstrual cycle, a cross-talk is triggered between the breast stem cells and the neighbouring cells. That causes increased activity and expansion in normal breast stem cells.

"The expansion is really quite surprising. It's more than a tenfold expansion," Dr. Khokha said.

Purna Joshi, lead author of the study and a graduate student, said the increased activity can allow for mutations that can transform cells into cancer cells.

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"The stem cells are considered to be the seeds for the initiation of breast cancer. So identifying signals and factors that govern stem cell numbers is actually key to identifying new ways of targeting those stem cells," Ms. Joshi said.

With a new understanding of how the hormone progesterone changes stem cells, the researchers say that further study will allow for new ways to target abnormal stem cells, which appear to be resistant to standard cancer therapies.

The idea that stem cells play a role in cancer is relatively new. Usually, stem cells are cast as stars in science. Some scientists have great hopes for stem cells because they have the ability to turn into every specialized cell that make up the human body. The human embryo is a plentiful source of stem cells. But as the body takes shape and matures, they become scarcer. Researchers hope that they may be able to treat a variety of diseases and repair damaged organs if they can harvest the relatively short supply of stem cells in the adult body.

But other researcher teams have uncovered evidence that stem cells also have a dark side. Their ability to reproduce infinitely could help explain the uncontrolled growth of cancerous tumours.

The cancer stem cell hypothesis is not universally accepted. But the new study goes a long way to explaining how the interaction of hormones and stem cells could give rise to breast cancer.

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