High hormone levels could be cause of breast cancer in BRCA gene carriers
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 carriers.
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 repair themselves.
“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 laboratory work.
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 Oncology. http://dx.doi.org/10.1016/
The research was funded by The Eve Appeal with contributions from the European Union, Cancer Research UK and the US National Institutes of Health.