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Many Canadian women are screened for breast cancer as part of their routine health care. Screening is important to find cancer at an early stage when it can usually be treated more easily and successfully, but it can only find cancer that has already developed. A preferable strategy is to prevent breast cancer from developing in the first place.
Thanks to research, we now know many of the factors that increase breast cancer risk including mutations in the BRCA genes. Women with these risk factors have higher-than-average odds of developing breast cancer yet there are few good ways to prevent the disease. Some lifestyle factors, such as maintaining a healthy diet, reducing alcohol use and limiting use of hormone replacement therapy, can lower the risk of breast cancer, and some women with BRCA mutations choose to have surgery to remove their breasts and ovaries to prevent the disease. A new study suggests a potential strategy to prevent breast cancer using epigenetics.
Changes to breast cells increase cancer risk
Epigenetics describes changes to genetic material that are not changes to the actual DNA sequence. These changes turn genes on and off, and they are important for healthy cell functions. But they can also lead to cancer if the changes happen at the wrong place or time.
A large team of researchers, including CCS-funded researchers based in Toronto, studied breast cells and their epigenetic changes to build comprehensive portraits of these cells and how they grow and change. In particular, they wanted to understand how progesterone – a hormone involved in the menstrual cycle, pregnancy and breast cell growth – is involved in epigenetics and breast cancer development.
Epigenetic drugs may reduce breast cancer development
Breast cells develop from unspecialized progenitor cells. During a woman’s menstrual cycle and pregnancy, progesterone prompts breast progenitor cells to multiply in order to develop breast tissue and mammary glands. While progesterone is essential for these important changes, it can also increase breast cancer risk.
Using their detailed analysis of breast cells, the researchers found that higher progesterone levels increased epigenetic changes in breast progenitor cells. With more epigenetic changes, there is a higher risk that cancer-blocking genes will be turned off and a tumour will start to grow.
Targeting epigenetic changes may be prevention strategy
Based on this result, the researchers tested a few drugs approved by the US Food and Drug Administration to target epigenetic changes in some forms of cancer. They found that, while a few drugs were able to stop the growth of progenitor cells, one epigenetic-targeting drug called decitabine delayed cancer development in a mouse model of cancer. This drug also reduced the number of progenitor cells in women with BRCA mutations.
This study helps to explain how progesterone drives epigenetic changes in breast progenitor cells to increase breast cancer risk. It also points to epigenetic changes in progenitor cells as a possible target for new prevention strategies. Some epigenetic drugs have been developed to treat other forms of cancer, such as myelodysplastic syndrome and certain forms of blood cancer. This research suggests that these drugs may also be useful to prevent breast cancer in women, particularly those with BRCA mutations.
Eileen Hoftyzer, BSc