Postmenopausal HRT ‐ a role for tamoxifen?

Abstract

International Journal of Clinical PracticeVolume 51, Issue 5 p. 267-267 EditorialFull Access Postmenopausal HRT - a role for tamoxifen? First published: 01 July 1997 https://doi.org/10.1111/j.1742-1241.1997.tb11456.xCitations: 2AboutReferencesRelatedInformationPDFSectionsREFERENCESCiting LiteraturePDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessClose modalShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Tamoxifen is the first of the selective estrogen receptor modulators (SERMS) used in clinical practice.1 The concept is one of oestrogen agonism on bone and the heart to maximise benefit with regard to osteoporosis and coronary artery disease (CAD) prevention and oestrogen antagonism on the breast and uterus, which would therefore minimise any risk of breast or uterine cancer. The only disadvantage with SERMS as a routine HRT is the absence of any beneficial effect on the menopausal vasomotor symptoms and the possibility of endometrial stimulation.2 Tamoxifen has been shown consistently to lower serum cholesterol in postmenopausal women with breast cancer.3 In one study, the mean decrease in total cholesterol was 12% and the mean decrease in LDL cholesterol 20%, whereas HDL was largely unaffected.4 Of interest, women with greater baseline cholesterols had greater decreases with tamoxifen. There is, of course, no point in pursuing these interesting findings unless they translate into clinical benefit. We know that CAD is the most important cause of death in women, exceeding the risk of breast cancer by more than five times, and we have evidence that HRT will reduce the cardiovascular risk by almost 50%, but anxieties have always been felt about long-term HRT use increasing breast cancer risk.5 A report by Grodstein and colleagues6 addresses the important issue of postmenopausal HRT and mortality in terms of cardiovascular and breast cancer risk. After adjusting for confounding factors, current hormone users had a lower risk of death (relative risk 0.63) than subjects who had never taken hormones, but the benefit decreased with long-term HRT use, being attentuated after 10 or more years of hormone therapy. Though lower cardiovascular mortality rates were maintained after 10 years, breast cancer mortality rose by 43%, eliminating the cardiovascular mortality benefit. The women in this study were aged 30-55 years at entry and the findings applied to all ages including the oldest women in the cohort at follow-up (ages 60-73 years) who would be considered to be at increased cardiovascular risk by age alone. The women who had the most cardiovascular benefits had other cardiovascular risk factors, while those at low risk had minimal, if any, benefit. The study also shows that women with a family risk of breast cancer are not at any greater risk of death if they take HRT. In practical terms, however, the protective effect of long-term HRT use on the cardiovascular system appears to be offset by an increased breast cancer risk, bringing into question the duration of conventional HRT. We can look at these findings in several ways, the simplest being to advise HRT for no longer than 10 years. Given that cardiovascular risk increases with age, should we be advocating a delay in the onset of conventional HRT to 55-60 years of age, so that we maximise the 10-year usage on cardiovascular benefit? But is there another way for HRT to continue its cardiovascular benefit while minimising the breast cancer risk? A closer look at tamoxifen is warranted. In a long-term study on breast cancer risk, tamoxifen reduced CAD mortality by approximately 50%.7 In another study of postmenopausal women with early stage breast cancer, tamoxifen significantly reduced hospital admissions due to cardiac disease, combining a substantial reduction in cardiac morbidity over two to five years of 32% with a low risk of death from breast cancer.8 As an adjuvant treatment for breast cancer tamoxifen reduces mortality by 25% and contralateral primary breast cancer incidence by 40%. The benefit on breast cancer continues, with evidence of protection against postmenopausal bone loss and reduced cardiovascular mortality, but there is a two- to six-fold increase in endometrial cancer.2 In absolute terms this represents an increase from one to two cases of endometrial cancer per 1000 tamoxifen-treated women per year. While this will incur screening costs, the incidence relative to the cardiovascular benefit with no adverse breast cancer risk makes tamoxifen an attractive alternative HRT, providing vasomotor symptoms arc not a limiting factor. In those with breast cancer or at increased risk of breast cancer, perhaps tamoxifen could be considered the HRT of choice, and certainly in those who have undergone a hysterectomy. In addition, should those at increased cardiovascular or bone loss risk who have completed 10 years of conventional HRT be switched to tamoxifen to enable them to continue to benefit without the breast cancer risk? SERMS are developing quickly with the aim of maximising the anti-tumour breast cancer action without a stimulating action on the endometrium. Tamoxifen is currently our only available agent and its role as an alternative HRT in selected patients needs both consideration and detailed evaluation. REFERENCES 1Nayfield SG, Karp JC, Ford LG et al. Potential role of tamoxifen in prevention of breast cancer. J Natl Cancer Inst 1991; 83: 1450– 1459. 2van Leeuwen F, Benraadt J, Coebergh JWW et al. Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet 1994; 343: 448– 452. 3Dewar JA, Horobin JM, Preece PE et al. Long-term effects of tamoxifen on blood lipid values in breast cancer. BMJ 1992; 305: 225– 226. 4Love RR, Wiebe DA, Newcomb PA et al. Effect of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann Intern Med 1991; 115: 860– 864. 5Jackson G. Coronary atery disease and women. BMJ 1994; 309: 555– 557. 6Grodstein F, Stampfer MJ, Colditz GA et al. Postmenopausal hormone therapy and mortality. N Engl J Med 1997; 336: 1769– 1775. 7Mc Donald CC, Stewart HJ. Fatal myocardial infarction in Scottish adjuvant tamoxifen trial. BMJ 1991; 303: 435– 437. 8Rutqvist LE, Mattsson A. for the Stockholm Breast Cancer Study Group. Cardiac and thromboembolic mortality among postmenopausal women with early-stage breast cancer in a randomised trial of adjuvant tamoxifen. J Natl Cancer Inst 1993; 85: 1398– 1406. Citing Literature Volume51, Issue5July-August 1997Pages 267-267 ReferencesRelatedInformation RecommendedMenopause and HRTJenna Friedenthal, Frederick Naftolin, Lila Nachtigall, Steven Goldstein, Evidence‐based Obstetrics and Gynecology, [1]Postmenopausal endometrial hyperplasia: role of danazol therapyL. Mariani, A. Sedati, R. Giovinazzi, R. Sindico, G. Atlante, International Journal of Gynecology & ObstetricsTamoxifen‐induced endometrial changes in postmenopausal women with breast carcinomaM Juneja, R Jose, A.N Kekre, F Viswanathan, L Seshadri, International Journal of Gynecology & Obstetrics