Title: Chemoprevention in BRCA1 mutation carrier – a proof of concept study (CIBRAC)
Sponsor: Belfast HSC Trust
Chief Investigator: Mr Stuart McIntosh, QUB/BHSCT
Investigators: Prof Paul Harkin, QUB, Dr Kienan Savage, QUB, Dr Gillian Prue, QUB
Research Fellow: Dr Aideen Campbell, QUB/BHSCT
Ethical Approval: Office for Research Ethics Committees Northern Ireland
Co-ordinating Centre: NI Cancer Trials Network at Belfast HSC Trust
Supported by: Cancer Research UK and Belfast Experimental Cancer Medicine Centre (ECMC)
Women with a BRCA1 gene mutation have a very high lifetime risk of developing breast and ovarian cancer. Currently, women wishing to reduce this risk are offered surgical removal of their breasts. The study aimed to develop a means of reducing the risk of cancer using drugs to lower levels of oestrogen, to avoid the problems associated with surgery.
The CIBRAC Study aimed to:
- Establish the feasibility of trial treatments as a chemopreventive strategy in BRCA1 mutation carriers and compliance to such treatments
- Establish tolerability of trial treatments and procedures
The study was open to recruitment between April 2017 and December 2019. Women were approached regarding the study, either in person through Family History Clinics in Belfast Trust, by post through the High Risk Breast Screening Programme at the Northern Trust or via BRCA LinkNI. This strategy aimed to reach the available population of women in Northern Ireland who were potentially eligible to participate in the study i.e. women age ≥18 years with a known pathogenic BRCA1 mutation, intact ovaries and no previous breast or ovarian carcinoma, with no history of malignancy and no previous risk reducing surgery.
The study intervention involved three months of either tamoxifen or goserelin/anastrazole, followed by a one-month washout period and then a crossover to a further three months of treatment. Breast tissue, core biopsies, urine and blood samples were obtained at baseline, after three months of treatment and at study conclusion.
In total, approximately 2% of the screened population consented to participate and were registered on the study. The study completed prior to meeting the recruitment target due to the low numbers of women who wished to take part.
A study amendment incorporated a qualitative study designed to assess participants’ reasons for accepting/declining trial participation.
The most commonly stated reasons for declining treatment related to lifestyle, with women reporting family or educational commitments, or generally being too busy to participate (7 women). Only one patient reported concern about side-effects as their reason for declining. However, the formal qualitative study that was incorporated into CIBRAC was also discontinued due to insufficient patients consenting to take part in the study interviews.
Despite not reaching the recruitment target, the study informed the primary objective and indicated that this particular chemopreventive strategy was not feasible in this population. Other studies have also indicated low interest in chemoprevention studies.
Personal and Public Involvement
This study illustrated the significance of Personal and Public Involvement (PPI) throughout the lifecycle of a clinical trial. Investigators liaised with the BRCA Link NI group at the concept stage of the research. Interestingly, no issues were raised relating to the acceptability of the therapeutic approach, and onward study development was supported. Investigators linked with both BRCA Link NI and the NI Cancer Research Consumer Forum (NICRCF) in the development of the Participant Information Sheet, Consent Form and Qualitative study participant documents. Hazel Carson, MBE, was PPI Representative in the study Trial Management Group. Hazel had a vital role including identifying ways to expand the reach of the study across the potentially eligible study population. Lack of recruitment, despite impactful PPI, suggests appropriate study quality and reinforces the conclusion that chemoprevention using a combination of goserelin and anastrazole to suppress oestrogen, as an approach for risk reduction in premenopausal women, was not feasible.
Mr Stuart McIntosh, NICTN and all involved in the conduct and management of the study wish to thank all the participants in both the intervention and the qualitative aspects of the study and all the women who considered participation in the study. Thanks also to BRCA Link NI, NICRCF, members of the Trials Management Group and study funders Cancer Research UK and Belfast ECMC.