An ovarian hormone drives changes in breast stem cells in mice, say Canadian researchers studying the implications for breast cancer risk.

The study, published in this week's online issue of the journal Nature, adds to scientists' understanding of how breast cancer may develop.

"What we now show is that there is a direct link between ovarian hormones, progesterone especially, and normal breast stem cells," said the study's principal investigator, Rama Khokha, a molecular biologist at the Ontario Cancer Institute.

The study shows how and when hormones affect breast stem cells during the menstrual cycle, Khokha added.

There are well-accepted links between ovarian hormones and breast cancer and mounting evidence that stem cells can be seeds for breast cancer development, said the study's lead author, Purna Joshi.

It was thought that stem cells in adult females are inactive and stayed constant in number, but the new findings show changes in breast stem cell numbers during the reproductive cycle.

Studies indicate that exposure to more reproductive cycles from early menstruation and late menopause increase a woman's risk for breast cancer, but the basis for the predisposition is unknown, the researchers said in the study. The new findings point to a role for progesterone levels.

"Our research demonstrates that when progesterone peaks during the second half of the menstrual cycle, it starts a cross-talk between stem cells and neighbouring cells that propels normal breast stem cells to expand in number, and may trigger an environment where cancer can begin," Joshi said.

The neighbouring cells respond with signals that affect the stem cells, Joshi added.

In the study, researchers mimicked the natural human reproductive cycle in mice to determine how progesterone affects breast stem cells.

"Our findings uncover a dynamic role for progesterone in activating adult mammary stem cells within the mammary stem cell niche during the reproductive cycle," the study authors concluded.

The researchers propose that expanded and cycling mammary stem cells provide "seeds" for accumulating DNA damage and cell changes leading to breast cancer.

Stem cells can be considered important targets for hormone-induced changes. For example, people with genetic mutations that increase susceptibility to breast cancer may be at even higher risk if their breast stem cells expand, but this idea still needs to be tested, Khokha said.

The research was supported by the Canadian Cancer Society Research Institute and the Canadian Breast Cancer Foundation.