© 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]
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