1. Jack Cuzick, Ph.D. Wolfson Institute of Preventive Medicine St Bartholomew’s Medical School London, United Kingdom Implementation Issues for Chemoprevention of Breast Cancer

2. thousands World-wide Burden of Cancer in Women GLOBOCAN 2002 Incidence Mortality

3. Breast Cancer Prevention Trials using Tamoxifen

4. Tamoxifen Overview : ER Positive Invasive Breast Cancer All Tam Prev IBIS Italian P1 Marsden.1.3.52 1 1.5 Odds Ratio

5. Outcome in 1000 women at high risk of breast cancer followed for 5 years No Treatment Tamoxifen for 5 years Breast Cancer VTE Endometrial Cancer 30 19 612 25

6. Prevention Trials using Raloxifene

7. ALL INVASIVE BREAST CANCERS, 0-10y SERM vs. placebo Fixed-effect model: -38.3% [-44.2%;-29.6%], p<0.001 Random-effect model: -39.3% [-51.1%;-24.7%], p<0.001 Test for heterogeneity: Q(8df) = 23.79, p=0.002 Hazard ratio.1.2.512510 Combined PEARL 50 mg PEARL 25 mg STAR RUTH MORE/CORE Marsden IBIS1 NSABP P1 Italian Tamoxifen vs. placebo Raloxifene vs. placebo Lasofoxifene vs. placebo

8. Contralateral Tumours in Aromatase Inhibitor Trials Odds Ratio (log scale).3.511.5 Combined B-33 MA-17 IES ITA/ARNO/ABCSG BIG 1-98 ATAC

9. New (Contralateral) Breast Primaries - AI adjuvant trials 47% 50% ATAC EBCTCG ? 75% 0 10 20 30 40 50 60 70 80 90 100 AnastrozoleTamoxifenPlacebo

10. MAP3 - Cumulative Incidence of Invasive Breast Cancer Goss et al NEJM, 2011

11. IBIS II- PREVENTION STRATUM n = 4,000 High Risk High Risk Post-menopausal women, aged 40-70. Placebo controlled 2-arm trial for high risk 5 Year Treatment RANDOMISATION PLACEBO ANASTROZOLE 1mg

12. Implementation Issues No agents licensed for prevention in Europe Tamoxifen and Raloxifene approved in the US Only manufacturer can apply for license All drugs off patent protection