Hormone replacement therapy and breast cancer: revisiting the issues.
OBJECTIVE
To assess current ideas about the benefits and risks of estrogen and hormone replacement therapy (ERT/HRT) in postmenopausal women.


METHODS
MEDLINE searches, supplemented by various texts, of the literature on HRT, ERT, and selective estrogen receptor modulators (SERMs): tamoxifen, toremifene, and raloxifene.


RESULTS
HRT is primarily used for improving quality of life in women suffering from vasomotor symptoms associated with menopause. HRT is beneficial in postmenopausal women for preventing cardiovascular disease, osteoporosis, and Alzheimer's disease. Review of meta-analyses of clinical trials showed that ERT/HRT ever-users (patients who have ever used ERT/HRT) did not have an increased risk of breast cancer, but current users did have an increased risk, with some studies reporting increasing risk with duration of ERT. No relationship was found between dose or the addition of progestin to ERT and increased breast cancer risk. Overall breast cancer mortality rates associated with HRT were decreased in current users. In general, HRT does not increase the risk of breast cancer in women with a family history of the disease, compared with those without a family history. New HRT strategies that could potentially prevent breast cancer are now being developed. The SERMs tamoxifen and toremifene appear to have positive clinical effects on bone and serum lipids; they are currently being investigated for use as breast cancer chemopreventive agents. Raloxifene, a new SERM used for the prevention of osteoporosis, is an alternative for women who cannot tolerate HRT. Unfortunately, these SERMS have anti-estrogenic effects and thus cause vasomotor adverse effects such as hot flashes and vaginal dryness. In addition, SERMs do not protect against heart disease or prevent osteoporosis as well as does HRT.


CONCLUSIONS
Presently, SERMs will not become first-line HRT, as the positive effects of ERT/HRT may outweigh any potentially increased risk of breast cancer. The development of new agents with pharmacodynamic profiles similar to that of ERT/HRT but lacking its adverse effects would be greatly beneficial for postmenopausal women.
DeGregorio
M W
MW
Department of Internal Medicine, University of California, Sacramento 95817, USA. mwdegregorio@ucdavis.edu
Taras
T L
TL
D000544:Alzheimer Disease / Q000517:prevention & control; D001943:Breast Neoplasms / Q000139:chemically induced*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008593:Menopause / Q000187:drug effects; D008875:Middle Aged; D010024:Osteoporosis / Q000517:prevention & control
D004965:Estrogen Antagonists; D004967:Estrogens