Abstract

Breast cancer is by far the commonest cancer in women, with an estimated 1.6 million new cases every year, and it is an ideal candidate in which to develop drug therapy for cancer prevention.

Two drugs, tamoxifen and raloxifene, are licensed for preventive therapy in the United States. More recently, two other selective oestrogen receptor modifiers (SERMs), lasofoxifene and arzoxifene, have been investigated in large prevention trials in osteoporotic women. In an individual patient overview of all these drugs, a 55% reduction in ER positive cancer in the five years of active treatment and a further 42% reduction in the next 5 years was seen. However no reduction in ER negative tumours has occurred.

Newer approaches are looking at the role of aromatase inhibitors. The MAP.3 trial evaluated exemestane and a 65% reduction in invasive tumours after a relatively short 30 months median follow up was seen. More recently the IBIS 2 trial using anastrozole has completed analysis of 3846 women with a median follow up of 5 years and reported a 53% reduction in all breast cancer, with a larger reduction in ER positive invasive breast cancer. Fracture rates were not significantly increased, and musculoskeletal and vasomotor symptoms were increased, but only by about 10%, with very high rates in the placebo arm.

As both of these classes of drugs (SERMs and AIs) have important side effects, it is important to focus their use among women most likely to benefit. Models have been developed to aid this decision and the Tyrer-Cuzick model appears to be one of the best at the moment. However, newer results have shown that mammographic breast density is an important predictor and a risk score combining the 67 currently identified risk SNPs may also add to predictive accuracy.