E17. The prevention of breast cancer

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A highly effective and increasingly common approach to reducing the incidence of and mortality from heart disease and stroke is the use of preventive therapy in highrisk individuals. The use of statins in people with high cholesterol levels and anti-hypertensives in those with high blood pressure has helped to reduce the death rate from heart disease by more than half and that from strokes by more than two thirds [1]. Breast cancer is by far the commonest cancer in women, with an estimated 1.4 million new cases every year, and it is an ideal candidate in which to begin to utilise this strategy for cancer prevention. Two drugs, tamoxifen and raloxifene, are licensed for preventive therapy in the United States. Both have been shown to reduce incidence by approximately 40%, but in a head-to-head comparison tamoxifen was about 25% more effective [2]. However, as these drugs are now off patent there seems to be no direct way for them to be licensed for prevention in Europe, although the National Institute for Health and Care Excellence (NICE) has now recommended their use for high-risk women in the UK, and they can be prescribed off-label. More recently two other selective oestrogen receptor (ER) modifiers (SERMs), lasofoxifene and arzoxifene, have been investigated in large prevention trials in which the primary outcome was the prevention of fractures in osteoporotic women. Both appear to be at least as effective as tamoxifen in breast cancer risk reduction, but lasofoxifene also showed large reductions in heart disease and fracture rates [3], making it an ideal candidate for preventive therapy. All of these drugs have recently been evaluated with extended follow-up in an individual patient overview [4]. The result shows a 55% reduction in ERpositive cancer in the 5 years of active treatment, but also a 42% reduction in the next 5 years, as a result of “carryover” benefits after treatment cessation (Figures 1 and 2). An important unanswered question is the duration of the carryover effect, as this enhances the benefits; however, side effects largely do not show a carryover, leading to a larger benefit/harm ratio. On the other hand, no reduction in ER-negative tumours has occurred, and in fact a marginally increased (14%, P = 0.09) incidence was seen (Figure 3). This may reflect tumours which would have appeared earlier as ER-positive tumours in the absence of treat