Research unlocks new key to hormones and cancer

WHILE a breast cancer diagnosis is no longer seen as a death sentence because of advances in treatment, advocates remain frustrated by poor outcomes in aggressive triple-negative cases.

Now, in research offering new hope to sufferers of basal-like triple-negative cancers, Australian researchers have discovered the role women's hormones play in their development.

The team from the Walter and Eliza Hall Institute identified a previously unknown link between the hormones and the epigenome, the chemical tags that tell DNA how to behave.

They discovered that the presence of hormones such as progesterone, which is most important for both puberty and pregnancy, can induce changes in thousands of genes.

Professor Jane Visvader, along with colleagues from the institute's breast cancer laboratory and bioinformatics division, found the hormones control the action of a key molecule that changes genetic material, EZH2.

"Sustained exposure to hormones over a lifetime could potentially lead to the initiation of a breast tumour through changes in the epigenome," Professor Visvader said. "And the EZH2 molecule is over-produced in many cancers, including breast cancers. Targeting these molecules may lead to new treatments".

The EZH2 molecule is vital in the development of normal breast tissue, both as the breasts grow during puberty and also as they change during pregnancy.

Professor Visvader said when the research team gave the mice progesterone, this increased the level of the molecule more than tenfold.

The team also examined what would happen if they blocked the action of the EZH2 molecule.

"The most striking effect found was that formation of the ductal tree in breast tissue was dramatically impaired," she said.

Almost all breast cancers originate in the lobules or ducts of the mammary glands.

"Blocking these hormone-induced changes in the epigenome with drugs may be an effective way of treating breast cancer," she said.

In a publication to be released on Saturday by the National Breast Cancer Foundation, 18 years of difference: how research has transformed a woman's experience of breast cancer, basal-like cancers are identified as among cancers where improvements have been few and far between.

While about 90 per cent of women with breast cancer now survive longer than five years, it is thought that only about 77 per cent of women with more aggressive basal-like or triple-negative cancers survive beyond five years.

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