Title: Introduction of breast cancer prevention with tamoxifen for high risk premenopausal women in the UK (Tamoxifen Prevention Study - TAM-P)
Funder: Department of Health (England)

Abstract: Background There are over 100,000 women at increased risk of breast cancer (>17% lifetime risk) currently attending Family History Clinics (FHC) in the UK. Between 17-85% of these will develop breast cancer depending on their baseline risk. These women receive annual mammography but little in the way of preventive approaches. Despite early diagnosis, many women at high-risk have a poor prognosis which means acceptable prevention strategies are required. Tamoxifen prevents breast cancer but is not licensed in the UK for this indication. The risk-benefit profile of tamoxifen is positive for premenopausal women who are the majority at familial risk. There is a need to introduce this drug into the clinic but before doing so we need to assess uptake and the women most likely to benefit. Aims Our primary aim is to determine the uptake of tamoxifen for prevention in all eligible premenopausal women in our high-risk clinic and to investigate the possibility that we can target treatment to women likely to benefit most. The specific aims are to, 1. determine the uptake of tamoxifen using a specially designed Decision Aid (DA). and to improve the DA using qualitative approaches, 2. investigate pre-defined biomarkers to predict women most likely to benefit, 3. assess women's reactions to continuation v discontinuation of treatment based on biomarkers, and 4. perform an economic analysis of the incremental costs and benefits of prescribing tamoxifen for prevention using different treatment targetting strategies compared with current practice. Plan of Investigation The study involves four Work-plans. W-P1. We will offer entry to the study to premenopausal women attending our FHC. Interviews with the first 15 recruited and 15 not recruited women will be used to improve the content and format of our Decision Aid. Potential improvements in uptake will be assessed during the second six month recruitment period. W-P2. Assessment of biomarkers of response to tamoxifen including change in mammographic density (MD) at one year and its relationship to other potential predictive biomarkers. W-P3. Qualitative assessment of attitudes of women to determination of treatment based on changes in biomarkers. W-P4. Economic model of prescribing preventative tamoxifen, using different treatment targetting strategies, compared with standard therapy. Potential Impact Breast Cancer is the major cause of death in young women. Tamoxifen will reduce breast cancer risk by at least 40%. This study will indicate the call for breast cancer prevention by tamoxifen in the target population and relative costs and patient benefits of this approach compared with current practice to women and NHS. It will also give an indication of whether we can predict benefit early using biomarkers or have to wait for the 1 year mammogram for prediction of preventive effect over the 5 year period of tamoxifen treatment. The whole study will inform licensing authorities, NICE, the profession (high-risk clinics nationally) and premenopausal women about the value of this chemoprevention approach of breast cancer. Deliverables will definitely be available from 3/4 W-Ps in 3 years.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS