PRELIMINARY-RESULTS FROM THE CANCER-RESEARCH CAMPAIGN TRIAL EVALUATING TAMOXIFEN DURATION IN WOMEN AGED 50 YEARS OR OLDER WITH BREAST-CANCER

Background: Although trials of postsurgical tamoxifen therapy for pati ents with breast cancer have convincingly demonstrated reductions in r elapse rates and improvements in survival, the optimal duration of the rapy is as yet unclear. Purpose: Our objective is to determine whether 2 or 5 years of tamoxifen therapy (20 mg/day orally) is preferable in the treatment of patients with early breast cancer. Methods: A random ized trial that was pragmatic in policy, allowing flexibility in prima ry treatment (i.e., type of surgery) and adjuvant therapy other than t amoxifen (i.e., radiotherapy or chemotherapy), was used to encourage m aximum participation of clinicians and patients. This design allowed c omparison of the two durations of tamoxifen therapy under conditions i n which they would subsequently be applied in clinical practice. The p atients were recruited from the oncology departments of participating hospitals in the U.K., Belgium, Poland, and Hong Kong. Those women who had completed an initial 2-year course of tamoxifen therapy after pri mary surgery and had not experienced a recurrence of breast cancer wer e asked to consider random assignment either to no further therapy or to an additional 3 years of tamoxifen. Follow-up reports (every 6 mont hs for 3 years after random assignment and then annually) were require d for all surviving study subjects. These reports recorded all breast cancer-related events (i.e., locoregional relapse and distant metastas is) or the development of new primary tumors (in the opposite breast o r at any other site). For patients who died, the date and cause of dea th were recorded. Event-free survival: overall survival: and time to l ocoregional relapse, distant metastasis, or the development of new pri mary cancers were end points for the analysis. Survival comparisons we re made by use of life tables and the logrank test. Reported P values are two-sided. Results: By December 31, 1994, 2937 patients had accept ed random assignment to treatment: 1470 were assigned to stop tamoxife n therapy after having received it for 2 years and 1467 were assigned to continue therapy for an additional 3 years (total, 5 years). An ana lysis was performed when the target for patient accrual had been reach ed, although the trial remains open. At a median follow-up of 2 years since the randomization, two treatment groups was detected (relative r isk = 0.69-1.15), but a statistically significant delay in the time to relapse for patients receiving the longer treatment was demonstrated (relative risk = 0.98). Conclusions and Implications: Our results sugg est that 5 years of tamoxifen therapy, but more evidence regarding the optimal duration of tamoxifen therapy must be obtained.