caa a22 4500 397563302 CHVBK 20180308164821.0 cr unu---uuuuu 161202e19961106xx s 000 0 eng 10.1093/jnci/88.21.1529 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.21.1529 Five Versus More Than Five Years of Tamoxifen Therapy for Breast Cancer Patients With Negative Lymph Nodes and Estrogen Receptor-Positive Tumors [Elektronische Daten] [Bernard Fisher, James Dignam, John Bryant, Arthur DeCillis, D. Lawrence Wickerham, Norman Wolmark, Joseph Costantino, Carol Redmond, Edwin R. Fisher, David M. Bowman, Luc Deschênes, Nikolay V. Dimitrov, Richard G. Margolese, André Robidoux, Henry Shibata, Jose Terz, A. H. G. Paterson, Merrill I. Feldman, William Farrar, James Evans, H. Lavina Lickley] Background: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment Purpose: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. Methods: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. Results: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P<.0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant diseasefree survival (76% versus 67%, P<.0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P =.007). Through 4 years after the reassignment of tamoxifentreated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P =.003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. Conclusions and Implications: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years. [J Natl Cancer Inst 1996; 88:1529-42] © Oxford University Press ARTICLES nationallicence Fisher Bernard National Surgical Adjuvant Breast and Bowel Project (NSABP) and Department of Surgery, University of Pittsburgh, PA aut Dignam James NSABP and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh aut Bryant John NSABP and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh aut DeCillis Arthur NSABP Medical Oversight, University of Pittsburgh aut Wickerham D. Lawrence NSABP and Allegheny General Hospital, Pittsburgh aut Wolmark Norman NSABP and Allegheny General Hospital, Pittsburgh aut Costantino Joseph NSABP and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh aut Redmond Carol Department of Biometry and Epidemiology, College of Medicine, Medical University of South Carolina Charleston aut Fisher Edwin R. Institute of Pathology, Shadyside Hospital Pittsburgh aut Bowman David M. Manitoba Cancer Foundation, Winnipeg, Canada aut Deschênes Luc St. Sacrement Hospital Quebec City, PQ, Canada aut Dimitrov Nikolay V. Department of Medicine, Michigan State University East Lansing aut Margolese Richard G. Jewish General Hospital Montreal PQ, Canada aut Robidoux André Hotel-Dieu, Montreal aut Shibata Henry Royal Victoria Hospital Montreal aut Terz Jose City of Hope Medical Center Duarte, CA aut Paterson A. H. G. Cross Cancer Institute Edmonton, AB, Canada aut Feldman Merrill I. Boston University MA aut Farrar William Ohio State University Columbus aut Evans James Geisinger Medical Center Danville, PA aut Lickley H. Lavina Women's College Hospital Toronto, ON, Canada aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/21(1996-11-06), 1529-1542 0027-8874 88:21<1529 1996 88 jnci https://doi.org/10.1093/jnci/88.21.1529 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.21.1529 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fisher Bernard National Surgical Adjuvant Breast and Bowel Project (NSABP) and Department of Surgery, University of Pittsburgh, PA aut NATIONALLICENCE 700 1- Dignam James NSABP and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh aut NATIONALLICENCE 700 1- Bryant John NSABP and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh aut NATIONALLICENCE 700 1- DeCillis Arthur NSABP Medical Oversight, University of Pittsburgh aut NATIONALLICENCE 700 1- Wickerham D. Lawrence NSABP and Allegheny General Hospital, Pittsburgh aut NATIONALLICENCE 700 1- Wolmark Norman NSABP and Allegheny General Hospital, Pittsburgh aut NATIONALLICENCE 700 1- Costantino Joseph NSABP and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh aut NATIONALLICENCE 700 1- Redmond Carol Department of Biometry and Epidemiology, College of Medicine, Medical University of South Carolina Charleston aut NATIONALLICENCE 700 1- Fisher Edwin R. Institute of Pathology, Shadyside Hospital Pittsburgh aut NATIONALLICENCE 700 1- Bowman David M. Manitoba Cancer Foundation, Winnipeg, Canada aut NATIONALLICENCE 700 1- Deschênes Luc St. Sacrement Hospital Quebec City, PQ, Canada aut NATIONALLICENCE 700 1- Dimitrov Nikolay V. Department of Medicine, Michigan State University East Lansing aut NATIONALLICENCE 700 1- Margolese Richard G. Jewish General Hospital Montreal PQ, Canada aut NATIONALLICENCE 700 1- Robidoux André Hotel-Dieu, Montreal aut NATIONALLICENCE 700 1- Shibata Henry Royal Victoria Hospital Montreal aut NATIONALLICENCE 700 1- Terz Jose City of Hope Medical Center Duarte, CA aut NATIONALLICENCE 700 1- Paterson A. H. G. Cross Cancer Institute Edmonton, AB, Canada aut NATIONALLICENCE 700 1- Feldman Merrill I. Boston University MA aut NATIONALLICENCE 700 1- Farrar William Ohio State University Columbus aut NATIONALLICENCE 700 1- Evans James Geisinger Medical Center Danville, PA aut NATIONALLICENCE 700 1- Lickley H. Lavina Women's College Hospital Toronto, ON, Canada aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/21(1996-11-06), 1529-1542 0027-8874 88:21<1529 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford