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Wales Online
Wales Online
National
Jane Kirby, PA Health Editor & Stephen Pitts

Women with Angelina Jolie gene could be monitored for breast cancer risk – study

Women with the “Angelina Jolie gene” could be closely monitored for their breast cancer risk and potentially avoid drastic surgery, research suggests.

The study found that women with the inherited faulty BRCA1 gene may be able to take the drug mifepristone to slow down the turnover in the cells that put them at risk of triple negative breast cancer. Mifepristone acts by blocking the effects of progesterone and is used for medical abortions where pills are taken to end the pregnancy.

According to the NHS, women with the faulty BRCA1 gene have a 65-79% lifetime risk of breast cancer and a 36-53% risk of ovarian cancer before the age of 80. The new research, published in Genome Medicine, was funded by the European Research Council and the gynaecological cancer charity the Eve Appeal.

During the study, researchers led by Prof Martin Widschwendter at the University of Innsbruck (LFUI) and University College London (UCL) found a “signature” of markers on DNA (called DNA methylation) which can indicate and help monitor the risk of breast cancer. The researchers used the WID-Breast29 test on samples taken from the breasts of women both with and without the BRCA gene alteration, who were all taking mifepristone at low doses.

All the women without the gene were found to have lower levels of progesterone – which is thought to help drive breast cancer at high levels – and cell turnover. The effect was also seen in around three-quarters of the women with a BRCA gene alteration.

Experts hope that these women with the faulty gene could be targeted with mifepristone to slow down their risk of developing breast cancer and keep their progesterone levels lower. In turn, this could mean they could delay or potentially avoid the need for a mastectomy. At present, women with the BRCA1 gene fault can opt to have both breasts removed to cut their cancer risk – something Jolie chose.

Prof Widschwendter said: “Progesterone is involved in the development of breast cancers with the worst prognoses. In the research published today, we assessed progesterone levels each day over an entire menstrual cycle and demonstrate that progesterone levels are significantly higher in BRCA1 mutation carriers; carrying this mutation confers a high risk of developing a breast cancer with a poor prognosis.

“Most importantly, we showed that drugs neutralising progesterone activity can reduce the cellular changes driving cancer development in normal breast tissue from young women. We are really excited about the prospects these findings open up for improved breast cancer prevention.”

Athena Lamnisos, chief executive of the Eve Appeal, says: “Everyone has heard of breast cancer and believe that treatment and outcomes have come on leaps and bounds in recent years. And that’s true with some breast cancer diagnoses – but not for the rarer and more aggressive forms of the disease. These new findings could be a game changer for what is currently a brutal diagnosis.”

Dr Kotryna Temcinaite, senior research communications manager at Breast Cancer Now, said: “Of the 55,000 women diagnosed with breast cancer in the UK each year around 5% of cases are caused by an inherited altered gene, which includes BRCA1 and BRCA2 genes. These exciting early research findings suggest drugs that neutralise progesterone activity could be a potential risk-reducing treatment for women with altered BRCA genes.

“Women with an altered BRCA1 gene are more at risk of triple negative breast cancer, which is harder to treat, so to be able to stop it developing would be hugely beneficial. We look forward to seeing further research to establish how viable this treatment could be and to better understand the potential side effects.”

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