[Breakthrough in breast cancer chemoprevention]

Breast cancer is the most frequent female malignant disease in developed countries. Various approaches are being developed for breast cancer prevention. Medical prevention called chemoprevention is reviewed. Prior to any intervention estimation of breast cancer risk is mandatory. For practical reasons distinction of two risk groups is useful. In the high risk group inherited gene mutation showing high penetrance may be suspected, while in the medium risk group hormonal factors play an important role. The antiestrogen tamoxifen has been extensively investigated in breast cancer and also tested for the prevention of breast cancer. The results of four randomized tamoxifen prevention studies have been published. In the largest, American trial the number of invasive or "in situ" breast cancers was halved by tamoxifen. Particularly estrogen receptor positive and relatively good prognosis breast cancers were reduced. Similar results were obtained in the "International Breast Intervention Study". Tamoxifen has been registered for breast cancer prevention for high risk individuals in the United States. The Italian and English ("Royal Marsden Hospital") studies did not prove significant preventative effect for tamoxifen that may be explained by the characteristics of the study protocols and study populations. Increased rates of endometrial cancer, thromboembolic events and cataract were observed under tamoxifen treatment, especially over the age of 50. Prevention has an increased importance in gene mutation carriers. Besides prophylactic mastectomy and close surveillance tamoxifen and bilateral oophorectomy or the use of gonadotropin releasing-hormone analogs seem efficient in this group. Various new chemoprevention strategies are under testing. Raloxifene and the aromatase inhibitors show advantage in menopausal women, the retinoid fenretinide and the gonadotropin releasing-hormone analogs seem promising for premenopausal individuals. The use of these agents are investigated in clinical trials. It is likely that not one single method will be applied for breast cancer prevention in the future. Preferably individual prevention strategies based on individual risk assessment will be developed.