Should tamoxifen be used in breast cancer prevention?

Breast cancer is the most commonly diagnosed cancer in women. The risk of developing breast cancer can be lowered by maintaining a healthy bodyweight and avoiding long-term use of combined estrogen and progestogen replacement after menopause. However, many women are at an increased risk of developing breast cancer secondary to age, early menarche, a family history of breast cancer or a personal history of benign breast disease. These women may now be offered tamoxifen as a chemoprevention therapy. Five years of tamoxifen treatment results in a reduction in the relative risk of developing estrogen receptor-positive breast cancer of 48%. This benefit outweighs the risk of tamoxifen-related adverse events for many healthy women. However, the benefit-risk ratio of tamoxifen chemoprevention varies for individual women. The randomized clinical trials evaluating standard-dose tamoxifen versus placebo as chemoprevention therapy are reviewed and analyzed to determine which particular women are most likely to benefit and least likely to experience a tamoxifen-related adverse event. Tamoxifen decreases the risk of breast cancer associated with aging, having a first-degree relative with disease, and a personal diagnosis of atypical ductal hyperplasia or lobular carcinoma in situ. Women who have had a hysterectomy and are at low risk of a thromboembolic event have a decreased risk of adverse effects associated with tamoxifen therapy. The strengths and weaknesses of the Gail model (frequently used to assess an individual's risk of developing invasive breast cancer over the next 5 years) are highlighted. A method for assessing the benefit-risk ratio for an individual woman is presented. Alternative breast cancer chemoprevention strategies are considered, including the use of aromatase inhibitors. This article discusses the pros and cons of these various preventive therapies and concludes that at this time, tamoxifen remains the gold standard for breast cancer prevention.