Serum RANKL and OPG in premenopausal women
Research type
Research Study
Full title
Serum RANKL and OPG in premenopausal BRCA1/2 mutation carriers and age-matched wild-type controls as a function of the menstrual cycle.
IRAS ID
162882
Contact name
Martin Widschwendter
Contact email
Sponsor organisation
UCL UCLH Joint Research Office
Research summary
Women with mutations in the ‘BReast CAncer 1’ (BRCA1) and ‘BReast CAncer 2’ (BRCA2) genes, have a very high lifetime risk of developing breast and ovarian cancer. The reason for the organ-specific effect of these mutations is unclear. We have previously shown that levels of the sex hormones estradiol (E2) and progesterone (P) differ between BRCA1/BRCA2 mutation-carriers and women without these mutations. It is thought that the sex hormone progesterone influences the risk of breast cancer in women without gene mutations via pathways incorporating the receptor activator of NF-?B ligand (RANKL), a molecule known to be involved in bone metabolism. An antibody against RANKL is already being used in clinical practice as a treatment for osteoporosis (reduced bone density associated with fractures) and we hypothesize that this antibody might also prove to be a useful drug for the prevention of breast cancer in women with BRCA1/BRCA2 mutations. In order to support this hypothesis, we want to compare the levels of RANKL and its related molecules in BRCA1/BRCA2 carriers and non-carrier controls. If the levels differ as predicted, this will provide the rationale to justify future work using an anti-RANKL antibody for the prevention of breast cancer in BRCA1/BRCA2 carriers. Currently such women can take Tamoxifen or aromatase inhibitors for breast cancer prevention, but these drugs are poorly tolerated due to their side effects and compliance is therefore poor. Anti-RANKL antibodies appear to be well tolerated and if shown to be effective in preventing breast cancer, may be more acceptable to women at increased risk of developing this disease.
REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
14/LO/1583
Date of REC Opinion
21 Aug 2014
REC opinion
Favourable Opinion