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

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

Breast Cancer Prevention Trials using Tamoxifen

Tamoxifen Overview : ER Positive Invasive Breast Cancer All Tam Prev IBIS Italian P1 Marsden Odds Ratio

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

Prevention Trials using Raloxifene

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 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

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

New (Contralateral) Breast Primaries - AI adjuvant trials 47% 50% ATAC EBCTCG ? 75% AnastrozoleTamoxifenPlacebo

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

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

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