High hormone levels could be cause of breast cancer in BRCA gene
24 October 2013
Abnormal levels of female hormones in the blood could be the trigger
causing women with the faulty genes BRCA 1 and BRCA 2 to develop breast
cancer instead of other cancers.
According to the study, by researchers at the University College
London (UCL) Department of Women’s Cancer, women with BRCA1 or BRCA2
mutations are exposed to different levels of the female hormones
oestradiol and progesterone. These are already known to be
risk-factors for breast and ovarian cancer.
The findings indicate that BRCA carriers have abnormal
hormone regulation, possibly due to a mechanism linked to the
altered BRCA genes in carriers’ ovaries. It is also possible that
BRCA gene alterations change the sensitivity of tissues to hormones.
More research into these mechanisms is needed.
The study also found that differences in the levels of hormones
correlated with the differences in the thickness of the uterus
lining, the endometrium, in the second half of the menstrual cycle.
The findings open up a new window of opportunity to prevent
breast and ovarian cancer in BRCA mutation carriers. The
authors anticipate that following further lab work, an existing drug
— currently used to treat osteoporosis — could be suitable for use
in a clinical trial of breast cancer prevention in BRCA1/2
Professor Martin Widschwendter, Head of the UCL Women’s Cancer
Department who led the research said: “We have shown for the first
time that cancer risk in BRCA1 and BRCA2 carriers
is not just caused by local defects in the ability of cells to
“An additional, systemic problem – abnormal levels of female
hormones in the bloodstream and altered downstream effects — is the
likely explanation as to why BRCA1/2 mutations carriers
develop breast and ovarian cancer rather than other cancers.”
Based on these findings, research has already begun into how
estrogens affect the Fallopian tubes, as this is where the majority
of “ovarian” cancers in BRCA1/2 carriers actually start.
The goal is to design drugs that might prevent the carcinogenic
effect of high concentrations of estrogens in the Fallopian tube.
The other female hormone, progesterone, is known to trigger
molecular changes in breast cells, specifically the production of
the growth factor protein RANKL, which lead to cancer. Blocking and
neutralizing RANKL by applying an antibody is an entire new concept
to prevent breast cancer and will be tested in women with
BCRCA1/2 mutations by Prof Widschwendter’s team after further
Dr Adam Rosenthal, also from the UCL Department of Women’s Cancer
and one of the study co-authors, said: “Many women with BRCA1
or BRCA2 mutations decide to have their breasts and ovaries
removed because of their high-risk status. Clearly this is a drastic
measure and there is an urgent need to develop less extreme
approaches for cancer prevention in such women.”
Helena Morrisey, chairman of The Eve Appeal is delighted with the
news. “We are proud to have funded this research which is a
fantastic step towards our ultimate goal of prevention of women’s
cancer. We are hopeful that based on this study and future
work funded by the Eve Appeal, women at high risk won’t have to go
through what Angelina Jolie went through.”
Widschwendter et al. The sex hormone system in
carriers of BRCA1/2 mutations: a case-control study. Lancet
The research was funded by The Eve Appeal with contributions from
the European Union, Cancer Research UK and the US National
Institutes of Health.