BRCA1 cancer study suggests alternative to major surgery

BRCA1 mutations put carriers at high risk of cancer by failing to protect cells
against the effects of high levels of oestrogen hormone found in breast and ovary tissue, researchers
have established.

A link between oestrogen and BRCA1 had long been suspected, but the study confirms it
and demonstrates the underlying mechanism.

The information could allow the development of preventative treatment strategies
using already available drugs as an alternative to the major surgery many women
choose to have to reduce their cancer risk.

One in 1,000 women in the UK have BRCA1
mutations that carry with them up to an 85 percent increased risk of breast cancer and
up to a 45 percent increased risk of ovarian cancer. BRCA1 mutations are
mostly inherited.

Currently, the only way to reduce the
increased cancer risk from a BRCA1 mutation is major surgery in the form
of double mastectomy (removal of both breasts) and oophorectomy (removal of
ovaries).

BRCA1 is a tumour suppressor gene and
normally works to maintain genome stability. As BRCA1 performs this function in
all cells, the researchers were interested in why mutations mainly led to
tumour formation in tissues regulated by oestrogen.

In cell culture experiments, the researchers showed
a clear link between high levels of hormones and DNA damage, which can cause cancer. They reported that oestrogen and its metabolites can cause double-strand
breaks in DNA in certain breast cells.

They also showed that BRCA1 is required to
repair these DNA breaks and also to regulate the expression of oestrogen-metabolising
enzymes in breast tissue, thus preventing DNA damage from oestrogen
metabolites.

Finally, the scientists looked at human cell
lines carrying BRCA1 mutations. They concluded that BRCA1-mutated cells in oestrogen-regulated
tissue, such as the breast and ovary, cannot counteract high levels of hormones
and their metabolites, and this leads to DNA damage and tumour formation.

'It's the first really credible evidence that
oestrogen is driving cancer in women with a BRCA1 gene mutation', said study
leader Dr Kienan Savage from Queen's University Belfast. 'Because of this
discovery, we now have the opportunity to propose an alternative treatment to
surgery. It also opens up the possibility of pausing treatment for a period for
women to have children, if desired'.

Drugs already exist that can reduce oestrogen
levels. The researchers now hope to secure funding to
test them as possible preventative treatments in clinical trials later in the
year.

The research, which took four years to
complete, was funded by Cancer Focus Northern Ireland and Cancer Research UK. Cancer
Focus Northern Ireland chief executive Roisin Foster said the research 'has the
potential in the foreseeable future to benefit women all over the world'.