© 1993 by Oxford University Press
Journal of the National Cancer Institute, Vol. 85, No. 17, 1398-1406,
September 1, 1993
© 1993 Oxford University Press
Cardiac and Thromboembolic Morbidity Among Postmenopausal Women With Early Stage Breast Cancer in a Randomized Trial of Adjuvant Tamoxifen
Oncologic Center, Karolinska Hospital Stockholm, Sweden
Lars E. Rutqvist, M.D., Oncologic Centre, Karolinska Hospital, S-104 01 Stockholm, Sweden.
BACKGROUND: Tamoxifen, which binds to estrogen receptors, is widely used as adjuvant therapy after surgery for early-stage breast cancer. Our previous randomized trial of adjuvant tamoxifen therapy for breast cancer showed a significant decrease of new, contralateral breast cancers in patients who received tamoxifen. Tamoxifen may also influence risk factors for cardiac and thromboembolic disease (e.g., serum cholesterol and antithrombin III).
PURPOSE: The purpose of this study was to assess morbidity from cardiac and thromboembolic disease among 2365 postmenopausal patients with early-stage breast cancer in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus no adjuvant endocrine therapy. Patients were entered in the study from November 1976 through December 1988.
METHODS: In our retrospective study, the analysis of morbidity was based on data from a computerized, population-based register of hospital admissions and discharge diagnoses. Mortality data were obtained from the Swedish National Central Bureau of Statistics. In the Stockholm study, treatment with tamoxifen was initiated within 4–6 weeks of modified radical mastectomy or breast-conserving surgery including axillary lymph node dissection and postoperative radiation therapy to the breast. In that randomized trial, 755 patients at low risk of death from breast cancer received adjuvant tamoxifen only; 760 received no treatment. In addition, 628 high-risk patients were randomly assigned to received adjuvant chemotherapy plus tamoxifen (173 patients) or postoperative radiotherapy plus tamoxifen (151) or, as a control, to receive chemotherapy (171) or postoperative radiation therapy (133), both without tamoxifen or other endocrine therapy. Median follow-up was 6 years.
RESULTS: Tamoxifen therapy resulted in a statistically significant reduced incidence of hospital admissions due to cardiac disease. The relative hazard (tamoxifen for 2 or 5 years versus control) was 0.68 (95% confidence interval [CI] = 0.48–0.97; P =.03). In the randomized comparison of 5 versus 2 years of tamoxifen, there was a statistically significant difference favoring the longer treatment (relative hazard = 0.37; 95% CI = 0.15–0.92; P =.03). There was little difference between the tamoxifen and control groups in terms of admissions due to thromboembolic disease.
CONCLUSIONS: These findings suggest that long-term adjuvant treatment with tamoxifen may result in substantial reduction of cardiac morbidity in patients with low risk of death from breast cancer as well as in women in chemopreventive studies who have high risk of developing breast cancer.
IMPLICATIONS: Our results support continuation of ongoing trials of tamoxifen therapy in these two groups of subjects. [J Natl Cancer Inst 85: 1398—1406, 1993]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Crivellari, Z. Sun, A. S. Coates, K. N. Price, B. Thurlimann, H. Mouridsen, L. Mauriac, J. F. Forbes, R. J. Paridaens, M. Castiglione-Gertsch, et al. Letrozole Compared With Tamoxifen for Elderly Patients With Endocrine-Responsive Early Breast Cancer: The BIG 1-98 Trial J. Clin. Oncol., April 20, 2008; 26(12): 1972 - 1979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. U. Lin and E. P. Winer Advances in Adjuvant Endocrine Therapy for Postmenopausal Women J. Clin. Oncol., February 10, 2008; 26(5): 798 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sun, A. K. Sharma, R. W. Dellinger, A. S. Blevins-Primeau, R. M. Balliet, G. Chen, T. Boyiri, S. Amin, and P. Lazarus Glucuronidation of Active Tamoxifen Metabolites by the Human UDP Glucuronosyltransferases Drug Metab. Dispos., November 1, 2007; 35(11): 2006 - 2014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zheng, D. Sun, A. K. Sharma, G. Chen, S. Amin, and P. Lazarus Elimination of Antiestrogenic Effects of Active Tamoxifen Metabolites by Glucuronidation Drug Metab. Dispos., October 1, 2007; 35(10): 1942 - 1948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Adess, R. Eisner, S. Nand, J. Godwin, H. L. Messmore Jr, and W. H. Wehrmacher Thromboembolism in cancer patients: pathogenesis and treatment. Clinical and Applied Thrombosis/Hemostasis, July 1, 2006; 12(3): 254 - 266. [Abstract] [PDF]
|
|
|
|
 |
|
 P. D. Ryan and P. E. Goss Adjuvant Hormonal Therapy in Peri- and Postmenopausal Breast Cancer Oncologist, July 1, 2006; 11(7): 718 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. U. Buzdar and J. Cuzick Anastrozole as an Adjuvant Endocrine Treatment for Postmenopausal Patients with Breast Cancer: Emerging Data Clin. Cancer Res., February 1, 2006; 12(3): 1037s - 1048s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 The Breast International Group (BIG) 1-98 Collabor A Comparison of Letrozole and Tamoxifen in Postmenopausal Women with Early Breast Cancer N. Engl. J. Med., December 29, 2005; 353(26): 2747 - 2757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Fisher, J. P. Costantino, D. L. Wickerham, R. S. Cecchini, W. M. Cronin, A. Robidoux, T. B. Bevers, M. T. Kavanah, J. N. Atkins, R. G. Margolese, et al. Tamoxifen for the Prevention of Breast Cancer: Current Status of the National Surgical Adjuvant Breast and Bowel Project P-1 Study J Natl Cancer Inst, November 16, 2005; 97(22): 1652 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Grainger and P. M. Schofield Tamoxifen for the Prevention of Myocardial Infarction in Humans: Preclinical and Early Clinical Evidence Circulation, November 8, 2005; 112(19): 3018 - 3024. [Full Text] [PDF]
|
|
|
|
|
|
B. Nordenskjold, J. Rosell, L.-E. Rutqvist, P.-O. Malmstrom, J. Bergh, N.-O. Bengtsson, T. Hatschek, A. Wallgren, and J. Carstensen Coronary Heart Disease Mortality After 5 Years of Adjuvant Tamoxifen Therapy: Results from a Randomized Trial J Natl Cancer Inst, November 2, 2005; 97(21): 1609 - 1610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Strasser-Weippl and P. E. Goss Advances in Adjuvant Hormonal Therapy for Postmenopausal Women J. Clin. Oncol., March 10, 2005; 23(8): 1751 - 1759. [Full Text] [PDF]
|
|
|
|
 |
|
 International Breast Cancer Study Group Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93 Ann. Onc., December 1, 2004; 15(12): 1749 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Angelopoulos, V Barbounis, S Livadas, D Kaltsas, and G Tolis Effects of estrogen deprivation due to breast cancer treatment Endocr. Relat. Cancer, September 1, 2004; 11(3): 523 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. de Medina, B. L. Payre, J. Bernad, I. Bosser, B. Pipy, S. Silvente-Poirot, G. Favre, J.-C. Faye, and M. Poirot Tamoxifen Is a Potent Inhibitor of Cholesterol Esterification and Prevents the Formation of Foam Cells J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 1165 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Crivellari, K. Price, R. D. Gelber, M. Castiglione-Gertsch, C.-M. Rudenstam, J. Lindtner, M. F. Fey, H.-J. Senn, A. S. Coates, J. Collins, et al. Adjuvant Endocrine Therapy Compared With No Systemic Therapy for Elderly Women With Early Breast Cancer: 21-Year Results of International Breast Cancer Study Group Trial IV J. Clin. Oncol., December 15, 2003; 21(24): 4517 - 4523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. He, M. E. Kargacin, G. J. Kargacin, and C. A. Ward Tamoxifen inhibits Na+ and K+ currents in rat ventricular myocytes Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H661 - H668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. E. Smith and M. Dowsett Aromatase Inhibitors in Breast Cancer N. Engl. J. Med., June 12, 2003; 348(24): 2431 - 2442. [Full Text] [PDF]
|
|
|
|
|
|
A. Decensi, C. Robertson, G. Viale, F. Pigatto, H. Johansson, E. R. Kisanga, P. Veronesi, R. Torrisi, M. Cazzaniga, S. Mora, et al. A Randomized Trial of Low-Dose Tamoxifen on Breast Cancer Proliferation and Blood Estrogenic Biomarkers J Natl Cancer Inst, June 4, 2003; 95(11): 779 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Simon, P. Boutouyrie, J.M. Simon, B. Laloux, C. Tournigand, A.I. Tropeano, S. Laurent, and P. Jaillon Influence of Tamoxifen on Carotid Intima-Media Thickness in Postmenopausal Women Circulation, December 3, 2002; 106(23): 2925 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Boccardo, A. Rubagotti, D. Amoroso, M. Mesiti, D. Romeo, C. Caroti, A. Farris, G. Cruciani, E. Villa, G. Schieppati, et al. Sequential Tamoxifen and Aminoglutethimide Versus Tamoxifen Alone in the Adjuvant Treatment of Postmenopausal Breast Cancer Patients: Results of an Italian Cooperative Study J. Clin. Oncol., November 15, 2001; 19(22): 4209 - 4215. [Abstract] [Full Text]
|
|
|
|
|
|
V. C. Jordan, S. Gapstur, and M. Morrow Selective Estrogen Receptor Modulation and Reduction in Risk of Breast Cancer, Osteoporosis, and Coronary Heart Disease J Natl Cancer Inst, October 3, 2001; 93(19): 1449 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Herrington, K. B. Brosnihan, B. E. Pusser, E. W. Seely, P. M. Ridker, N. Rifai, and D. B. MacLean Differential Effects of E and Droloxifene on C-Reactive Protein and Other Markers of Inflammation in Healthy Postmenopausal Women J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4216 - 4222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Shapiro and A. Recht Side Effects of Adjuvant Treatment of Breast Cancer N. Engl. J. Med., June 28, 2001; 344(26): 1997 - 2008. [Full Text] [PDF]
|
|
|
|
|
|
S. C. Clarke, P. M. Schofield, A. A. Grace, J. C. Metcalfe, and H. L. Kirschenlohr Tamoxifen Effects on Endothelial Function and Cardiovascular Risk Factors in Men With Advanced Atherosclerosis Circulation, March 20, 2001; 103(11): 1497 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cushman, J. P. Costantino, R. P. Tracy, K. Song, L. Buckley, J. D. Roberts, and D. N. Krag Tamoxifen and Cardiac Risk Factors in Healthy Women : Suggestion of an Anti-inflammatory Effect Arterioscler. Thromb. Vasc. Biol., February 1, 2001; 21(2): 255 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Reis, J. P. Costantino, D. L. Wickerham, E. Tan-Chiu, J. Wang, and M. Kavanah Cardiovascular Effects of Tamoxifen in Women With and Without Heart Disease: Breast Cancer Prevention Trial J Natl Cancer Inst, January 3, 2001; 93(1): 16 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bonneterre, B. Thurlimann, J. F. R. Robertson, M. Krzakowski, L. Mauriac, P. Koralewski, I. Vergote, A. Webster, M. Steinberg, and M. von Euler Anastrozole Versus Tamoxifen as First-Line Therapy for Advanced Breast Cancer in 668 Postmenopausal Women: Results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability Study J. Clin. Oncol., November 15, 2000; 18(22): 3748 - 3757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Osborne and S. A. W. Fuqua Selective Estrogen Receptor Modulators: Structure, Function, and Clinical Use J. Clin. Oncol., September 17, 2000; 18(17): 3172 - 3186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. U. Buzdar Tamoxifen's Clinical Applications: Old and New Arch Fam Med, September 1, 2000; 9(9): 906 - 912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Herrington, B. E. Pusser, W. A. Riley, T. Y. Thuren, K. B. Brosnihan, E. A. Brinton, and D. B. MacLean Cardiovascular Effects of Droloxifene, a New Selective Estrogen Receptor Modulator, in Healthy Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1606 - 1612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Extermann, L. Balducci, and G. H. Lyman What Threshold for Adjuvant Therapy in Older Breast Cancer Patients? J. Clin. Oncol., April 1, 2000; 18(8): 1709 - 1717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. louffe Jr. Selective Estrogen Receptor Modulators (SERMs) in Clinical Practice Reproductive Sciences, January 1, 2000; 7(1_suppl): S38 - S46. [Abstract] [PDF]
|
|
|
|
 |
|
 S. R. Cummings, S. Eckert, K. A. Krueger, D. Grady, T. J. Powles, J. A. Cauley, L. Norton, T. Nickelsen, N. H. Bjarnason, M. Morrow, et al. The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results From the MORE Randomized Trial JAMA, June 16, 1999; 281(23): 2189 - 2197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. C. Jordan and M. Morrow Tamoxifen, Raloxifene, and the Prevention of Breast Cancer Endocr. Rev., June 1, 1999; 20(3): 253 - 278. [Abstract] [Full Text]
|
|
|
|
|
|
F. Cosman and R. Lindsay Selective Estrogen Receptor Modulators: Clinical Spectrum Endocr. Rev., June 1, 1999; 20(3): 418 - 434. [Abstract] [Full Text]
|
|
|
|
|
|
R. T. Chlebowski, D. E. Collyar, M. R. Somerfield, and D. G. Pfister American Society of Clinical Oncology Technology Assessment on Breast Cancer Risk Reduction Strategies: Tamoxifen and Raloxifene J. Clin. Oncol., June 1, 1999; 17(6): 1939 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Mortimer, L. Boucher, J. Baty, D. L. Knapp, E. Ryan, and J. H. Rowland Effect of Tamoxifen on Sexual Functioning in Patients With Breast Cancer J. Clin. Oncol., May 1, 1999; 17(5): 1488 - 1488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Anker, H. Refsum, P. M. Ueland, D. C. Johannessen, E. A. Lien, and P. E. Lonning Influence of Aromatase Inhibitors on Plasma Total Homocysteine in Postmenopausal Breast Cancer Patients Clin. Chem., February 1, 1999; 45(2): 252 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Osborne Tamoxifen in the Treatment of Breast Cancer N. Engl. J. Med., November 26, 1998; 339(22): 1609 - 1618. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Christ and M. Wehling Cardiovascular steroid actions: swift swallows or sluggish snails? Cardiovasc Res, October 1, 1998; 40(1): 34 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Heilmann, G.-F. V. Tempelhoff, and D. Schneider State-of the-Art Review : Prevention of Thrombosis in Gynecologic Malignancy Clinical and Applied Thrombosis/Hemostasis, July 1, 1998; 4(3): 153 - 159. [PDF]
|
|
|
|
 |
|
 J. I. Macgregor and V. C. Jordan Basic Guide to the Mechanisms of Antiestrogen Action Pharmacol. Rev., June 1, 1998; 50(2): 151 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Walsh, L. H. Kuller, R. A. Wild, S. Paul, M. Farmer, J. B. Lawrence, A. S. Shah, and P. W. Anderson Effects of Raloxifene on Serum Lipids and Coagulation Factors in Healthy Postmenopausal Women JAMA, May 13, 1998; 279(18): 1445 - 1451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Lamberts, A. W. van den Beld, and A. van der Lely The Endocrinology of Aging Science, October 17, 1997; 278(5337): 419 - 424. [Abstract] [Full Text]
|
|
|
|
|
|
J. K. Williams, E. K. Honore, and M. R. Adams Contrasting Effects of Conjugated Estrogens and Tamoxifen on Dilator Responses of Atherosclerotic Epicardial Coronary Arteries in Nonhuman Primates Circulation, September 16, 1997; 96(6): 1970 - 1975. [Abstract] [Full Text]
|
|
|
|
|
|
J. Reckless, J. C. Metcalfe, and D. J. Grainger Tamoxifen Decreases Cholesterol Sevenfold and Abolishes Lipid Lesion Development in Apolipoprotein E Knockout Mice Circulation, March 18, 1997; 95(6): 1542 - 1548. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. C McDonald, F. E Alexander, B. W Whyte, A P. Forrest, and H. J Stewart Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial BMJ, October 14, 1995; 311(7011): 977 - 980. [Abstract] [Full Text]
|
|