Chemoprevention of breast cancer: implications for postmenopausal women.

Estrogen administration is associated with reduction in perimenopausal symptoms and the risk for several conditions affecting postmenopausal women. As estrogen administration also increases the risk for breast cancer, a common dilemma facing many women and their physicians is whether to use estrogen replacement therapy (ERT), a selective estrogen receptor modulator (SERM) that antagonises estrogenic effects in breast tissue but retains some estrogen agonist properties in other organs, or neither. For women with average to moderate risk of breast cancer and with perimenopausal symptoms, ERT may be the best short-term choice. For very high-risk women (>1% per year) with menopausal symptoms, alternatives to ERT might be offered and tried first. A diagnosis of ductal carcinoma in situ or invasive breast cancer within the last 2 to 5 years should be considered a relative contraindication for ERT unless the tumour was estrogen receptor negative. High-risk women without menopausal symptoms are the best candidates for the only currently approved drug for breast cancer risk reduction, tamoxifen. Although the drug is approved for women with a 5-year risk of breast cancer > or = 1.7% (0.34% per year), postmenopausal women most likely to experience a favourable benefit/risk ratio are those with a Gail estimated risk of >0.5% per year without a uterus or >1% per year if they retain their uterus. Tamoxifen should not be used in women with prior history of thromboembolic or precancerous uterine conditions. Tamoxifen is often used in Europe in conjunction with transdermal ERT in hysterectomised women without obvious loss of efficacy or increased risk of thromboembolism. Raloxifene is a second generation SERM with estrogen-like agonist effects on bone but with less uterine estrogen agonist activity than tamoxifen. Raloxifene may have less potent breast antiestrogenic effects than tamoxifen, particularly in a moderate- to high-estrogen environment. Raloxifene is approved for use in reducing risk of osteoporosis, but not breast cancer. Whether it is as effective as tamoxifen in reducing breast cancer risk in postmenopausal women is the subject of a current trial. All women regardless of breast cancer risk are advised to employ nonpharmacological risk reduction measures, including normalisation of bodyweight, exercise, adequate calcium and vitamin D intake, and avoidance of smoking and alcohol. The preventive options are best weighed during an individualised consultation where a woman's menopausal symptoms and risk for breast cancer and other diseases can be examined, and the options for improving postmenopausal health can be discussed.