Hormone Replacement Therapy and Breast Cancer. A Review of Current Knowledge

More than 50 studies looking at the relationship between hormone replacement therapy and breast cancer have been published. Overall the results are reassuring. There is no evidence of an increased risk of breast cancer after ever use of exogenous estrogens. However, when long term use (i.e. use for more than 10 to 15 years) is considered the majority of data are compatible with a small increase in the risk, in the magnitude of 30 to 50%, possibly limited to women who are currently receiving hormone replacement therapy or who have recently stopped such therapy. This would translate into an increase in the absolute risk of developing breast cancer of 3 to 4% of among postmenopausal women in the Western world. No consistent evidence exists on differing risks of breast cancer with different types of estrogens, and no clear dose-relationship has been found. Risk estimates for combined estrogen-progestogen regimens have been of the same magnitude as for estrogens alone; thus, no clear evidence of a protective effect of the addition of a progestogen has been found. Investigations into a possible interaction between estrogen supplementation and other known risk factors for breast cancer have not yielded any consistent results. Cancers that develop during estrogen therapy have been found to be associated with a favourable prognosis. This could be explained in part by better medical surveillance, and early detection, but may also represent an effect of the treatment itself. Despite the increased incidence of breast cancer after long term hormone replacement therapy, no increased mortality from breast cancer among estrogen users has been found. Thus, on the whole, data seem reassuring. The small increase in the risk of breast cancer after long term hormone replacement therapy use, with no concomitant increase in mortality, is likely to be outweighed by the positive effects of estrogens on the symptoms of the menopause and osteoporosis, and the protective effects of such therapy against cardiovascular disease.