Continued Breast Cancer Risk Reduction in Postmenopausal Women Treated with Raloxifene: 4-Year Results from the MORE Trial

Springer Science and Business Media LLC - Tập 65 - Trang 125-134 - 2001
Jane A. Cauley1, Larry Norton2, Marc E. Lippman3, Stephen Eckert4, Kathryn A. Krueger5, David W. Purdie6, Jordi Farrerons7, Avraham Karasik8, Dan Mellstrom9, Kong Wah Ng10, Jan J. Stepan11, Trevor J. Powles12, Monica Morrow13, Alberto Costa14, Sheryl L. Silfen5, Erin L. Walls5, Henry Schmitt5, Douglas B. Muchmore4, V. Craig Jordan15
1Department of Epidemiology, University of Pittsburgh USA
2Department of Breast Cancer Medicine, Memorial Sloan Kettering Cancer Center, USA
3Lombardi Cancer Center and Division of Imaging Science, Department of Radiology, Georgetown University Medical Center, Washington, USA
4Applied Logic associates, Inc., Houston, USA
5Eli Lilly and Co, Indianapolis, USA
6Centre for Metabolic Bone Disease, University of Hull and the Royal Hull Hospitals, Hull, England
7Hospital Santa Cruz & San Pablo, Barcelona, Spain
8Chaim Sheba Medical Center, Tel Hashomer, Israel
9Department of Geriatrics, Sahlgrenska University Hospital, Göteborg, Sweden
10The University of Melbourne, Department of Medicine, Australia
11Charles University, 3rd Department of Internal Medicine, Praha, Czech Republic
12Breast Unit, Royal Marsden NHS Trust Hospital, London, UK
13Department of Surgery, Northwestern University Medical School, Chicago, USA
14European Institute of Oncology, Milano, Italy
15Robert H. Lurie Cancer Center, Northwestern University; for The Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators, Chicago, USA

Tóm tắt

Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60mg/day, and 2,572 raloxifene 120mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.

Tài liệu tham khảo

Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90: 1371-1388, 1998

Barakat RR: Tamoxifen and the endometrium. Cancer Treat Res 94: 195-207, 1998

Cohen FJ, Watts S, Shah A, Akers R, Plouffe L: Uterine effects of three-year raloxifene therapy in postmenopausal women under age 60. Obstet Gynecol 95: 104-110, 2000

Cummings S, Eckert S, Krueger K, Grady D, Powles T, Cauley J, Norton L, Nickelsen T, Bjarnason N, Morrow M, Lippman M, Black D, Glusman J, Costa A, Jordan VC: The effect of raloxifene on risk of breast cancer in postmenopausal women. JAMA 281: 2189-2197, 1999

National Institutes of Health, Office of Cancer Communications: Publication of the MORE Trial Results Support Study of Tamoxifen and Raloxifene (STAR). Press Release of National Cancer Institute, 1999

Delmas PD, Bjarnason NH, Mitlak BH, Ravoux A-C, Shah AS, Huster WJ, Draper M, Christiansen C: Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 337: 1641-1647, 1997

Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud K, Avioli LV, Lips P, Cummings SR: Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. JAMA 282: 637-645, 1999

Walsh BW, Kuller LH, Wild RA, Paul S, Farmer M, Lawrence JB, Shah AS, Anderson PW: Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. JAMA 279: 1445-1451, 1998

Barrett-Connor E, Wenger NK, Grady D, Mosca L, Collins P, Kornitzer M, Cox DA, Moscarelli E, Anderson PW: Hormone and nonhormone therapy for the maintenance of postmenopausal health: the need for randomized controlled trials of estrogen and raloxifene. J Womens Health 7: 839-847, 1998

Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, Rotmensz N, Boyle P: Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet 352: 93-97, 1998

Powles T, Eeles R, Ashley S, Easton D, Chang J, Dowsett M, Tidy A, Viggers J, Davey J: Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 352: 98-101, 1998

Grese TA, Sluka JP, Bryant HU, Cullinan GJ, Glasebrook AL, Jones CD, Matsumoto K, Palkowitz AD, Sato M, Termine JD, Winter MA, Yang NN, Dodge JA: Molecular determinants of tissue selectivity in estrogen receptor modulators. Proceedings of the Natl Acad Sci USA 94: 14105-14110, 1997

Brzozowski AM, Pike ACW, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M: Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389: 753-758, 1997

Davies G, Huster WJ, Lu Y, Plouffe L, Lakshmanan M: Adverse events reporters by post menopausal women in controlled trials with raloxifene. Obstet Gynecol 93: 558-565, 1999

Greendale GA, Reboussin BA, Sie A, Singh HR, Olson LK, Gatewood O, Bassett LW, Wasilauskas C, Bush T, Barrett-Connor E: Effects of estrogen and estrogen-progestin on mammographic parenchymal density. Ann Intern Med 130: 262-269, 1999

Kavanagh AM, Mitchell H, Giles GG: Hormone replacement therapy and accuracy of mammographic screening. Lancet 355: 270-274, 2000

Freedman M, San Martin J, O'Gorman J, Eckert S, Lippman ME, Lo S-C, Walls EL, Zeng J: Digitized mammography: A clinical trial of post menopausal women randomized to raloxifene, estrogen, or placebo, J Natl Cancer Inst, (In press)

Cauley JA, Lucas FL, Kuller LH, Vogt MT, Browner WS, Cummings SR: Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures. Study of Osteoporotic Fractures Research Group. JAMA 276: 1404-1408, 1996

Zhang Y, Kiel DP, Kreger BE, Cupples LA, Ellison RC, Dorgan JF, Schatzkin A, Levy D, Felson DT: Bone mass and the risk of breast cancer among postmenopausal women. N Engl J Med 336: 611-617, 1997

Cauley JA, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR: Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Study of Osteoporotic Fractures Research Group. Ann Intern Med 130: 270-277, 1999

Ries LAG, Kosary CL, Hankey BF, Miller BA, Clegg L, Edwards BK (eds): SEER Cancer Statistics Review, 1973-1996. National Cancer Institute, Bethesda, MD, 1999

Cohen FJ, Lu Y: Characterization of hot flashes reported by healthy postmenopausal women receiving raloxifene or placebo during osteoporosis prevention trials. Maturitas 34: 65-73, 2000

Tomas E, Kauppila A, Blanco G, Apaja-Sarkkinen M, Laatikainen T: Comparison between the effects of tamoxifen and toremifene on the uterus in postmenopausal breast cancer patients. Gynecol Oncol 59: 261-266, 1995

Dijkhuizen FPHLJ, Brolmann HAM, Oddens BJJ, Roumen RMH, Coebergh JWW, Heintz APM: Transvaginal ultrasonography and endometrial changes in postmenopausal breast cancer patients receiving tamoxifen. Maturitas 25: 45-50, 1996

Nolvadex (tamoxifen citrate) Package Insert. 1998

Gull B, Karlsson B, Wikland M, Milsom I, Granberg S: Factors influencing the presence of uterine cavity fluid in a random sample of asymptomatic postmenopausal women. Acta Obstet Gynecol Scand 77: 751-757, 1998

Vuento MH, Pirhonen JP, Makinen JI, Tyrkko JE, Laippala PJ, Gronroos M, Salmi TA: Endometrial fluid accumulation in asymptomatic postmenopausal women. Ultrasound in Obstet Gynecol 8: 37-41, 1996

Goldstein SR: Postmenopausal endometrial fluid collections revisited: look at the doughnut rather than the hole. Obstet Gynecol 83: 738-740, 1994

Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E: Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 280: 605-613, 1998

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Springer Science and Business Media LLC

Tập 65

125-134

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