Women with germline BRCA1 mutations have a high lifetime risk of breast cancer. These women predominantly develop triple-negative breast cancers.

Risk-reduction strategies include risk-reducing mastectomy (RRM) or chemoprevention with selective estrogen receptor modulators (SERMs). However, SERMs have not been shown to reduce the incidence of oestrogen receptor negative breast cancers, hence it is unlikely that SERMs will reduce the risk of cancer in this group.

Preclinical data suggests exposure to oestrogen and its metabolites causes DNA double strand breaks (DSBs), driving genomic instability, an early hallmark of BRCA1-related breast cancer. Additionally this study found that BRCA1 suppresses estrogen metabolism, is required for the repair oestrogen induced DSBs and that BRCA1 haploinsufficiency leads to increased genomic instability following exposure to oestrogen metabolites.

Therefore, an approach which lowers circulating oestrogen levels and reduces oestrogen metabolite exposure may prove a successful chemopreventive strategy by reducing genomic instability in BRCA1 heterozygous breast tissue.



Twelve pre-menopausal BRCA1 mutation carriers will be treated either with goserelin and anastrazole (6) or tamoxifen (6) for three months. Breast core biopsies, plasma and urine samples will be taken at baseline and at three months. After a one month washout period patients will cross over to the other treatment arm for a further three months and biological sampling repeated at the conclusion of treatment. Quality of life and treatment compliance data will be collected.

The study's aims are to:

  • Establish treatment compliance and quality of life during treatment
  • Establish changes in DNA damage in breast tissue during oestrogen supression using immunohistochemistry and comet assays
  • Establish changes in oestrogen/oestrogen metabolite levels in breast tissue and plasma using ultra-performance liquid chromatography mass spectrometry
  • Assess changes in proliferation in breast tissue during oestrogen suppression

Inclusion criteria


  • Age >18 yeArs
  • Premenopausal
  • Known pathogenic BRCA1 mutation
  • Intact ovaries
  • No previous breast/ovarian carcinoma
  • No previous use of chemoprevention

Exclusion criteria:

  • BRCA1 mutation of uncertain significance
  • Personal history of breast or ovarian carcinoma
  • Previous risk-reducing breast or ovarian surgery
  • Post-menopausal
  • Concomitant use of alternative chemoprevention regimens
  • Concomitant use of other hormonal agents (e.g.COCP)
  • Contra-indications to breast core biopsies (e.g. anticoagulation, anti-platelet agents etc)
  • Inability to give informed consent

Further information


The CIBRAC trial is now open and you can find more information on the Cancer Research UK website here.

For any additional information about this trial please contact Stuart McIntosh, Chief Investigator, at