Table 1

Trial objectives and endpoints

Primary objective	Primary endpoint
To establish the acceptability of trial treatments as a chemopreventive strategy in BRCA1 mutation carriers and compliance.	Percentage of patients given patient information sheet who consent to trial entry. Measurement of compliance with treatment using patient medication cards.
Secondary objective	Secondary endpoint
To establish tolerability of trial treatments and procedures.	Measurement of patient quality of life using questionnaires at baseline and after completion of each treatment arm. Recording of adverse events that occur during treatment.
Exploratory objectives	Exploratory endpoints
To establish the potential of chemopreventive agents to reduce oestrogen-mediated DNA damage in breast tissue in BRCA1 mutation carriers.	Measurement of DNA damage in breast tissue using comet assays and immunohistochemical assays at baseline and after completion of each treatment arm.
To establish the effect of treatment on oestrogen metabolite levels in breast tissue, urine and serum.	Measurement of breast, blood and urinary oestrogen metabolite levels using ultra performance liquid chromatography tandem mass spectrometry at baseline and after completion of each treatment arm.
To explore the mechanism of oestrogen-mediated DNA damage in breast tissue in BRCA1 mutation carriers.	Analysis of breast tissue samples using alternative methods of DNA damage assessment.
To explore the relationship between oestrogen metabolite concentration in serum and urine and DNA damage in breast tissue in BRCA1 mutation carriers.	Analysis of breast tissue, urine and blood samples for proxies of oestrogen levels and DNA damage.
To explore potential biomarkers of chemoprevention efficacy.	Analysis of breast tissue, urine and blood samples for potential biomarkers of chemopreventive efficacy.