ASCO--Data from a large multi-center European study has confirmed the superiority of five years of tamoxifen(Drug information on tamoxifen) (Nolvadex) therapy as opposed to two or three years in postmenopausal breast cancer patients. When longer follow-up data are available, the trial will be able to determine whether even longer duration of tamoxifen (12 to 13 years) might provide additonal benefits.
The findings confirm those of a smaller Scottish study reported at the ASCO meeting last year, as well as the findings of other studies in the literature.
This study involved almost 3,800 postmenopausal early breast cancer patients, each of whom had taken tamoxifen for two to three years prior to enrollment in the trial.
The rationale of the trial was based on clinical results as they were known in 1985 when the trial was organized. "Adjuvant tamoxifen is known to result in a significant reduction in the odds of recurrence and mortality in early breast cancer. However, the optimal duration has not been determined and remains controversial," said Dr. Thierry Delozier, of the Centre François Baclesse, Caen, France, in his presentation of the data at the ASCO integrated session on breast cancer.
At randomization, half the patients stopped taking tamoxifen and half continued treatment. The trial was conducted between September 1986 and May 1995.
Because so few events had occurred at 10 years, the protocol was modified in February of this year to discontinue tamoxifen 10 years after randomization. As a result, the trial will compare the impact of two to three years of therapy versus 12 to 13 years (follow-up is complete for 4 to 5 years), Dr. Delozier said.
About two thirds of the patients were node positive, and a similar number was positive for estrogen receptors. About 30% of patients received adjuvant chemotherapy. Tamoxifen dosage ranged from 10 to 70 mg daily. The majority of patients received 20 to 40 mg daily.
Median follow-up in the trial has reached 48 to 49 months for both patient groups. The mean duration of tamoxifen therapy was 30 months in patients who discontinued therapy at randomization and 70 months in the patients who continued hormonal therapy.
Thus far, no difference in overall survival has emerged, as about 80% of patients in both groups remain alive. However, the longer duration of tamoxifen therapy significantly improved five-year disease-free survival, 80% versus 72% (P = .002).
The incidence of endometrial cancer was virtually identical in the two groups, as 13 patients developed the cancer in the short-term tamoxifen group versus 12 in the long-term cohort. Contralateral breast cancer occurred more often in the short-term therapy group, 44 cases versus 27 in patients who continued treatment.
Analysis of the data by different dosages showed an advantage for the long-term therapy group at 30 mg daily but not for 20 mg or 40 mg, the most common doses.
Disease-free survival had an unexpected association with nodal status. Long-term therapy benefited patients who had positive lymph nodes but not those with negative nodes. Dr. Delozier had no explanation for the finding.
The results leave unanswered the question of optimal duration of tamoxifen therapy. "We need further follow-up to assess the value of longer duration of therapy with tamoxifen," he said. "I think the only recommendation we can make at this point is that tamoxifen should be given for at least five years, but the question of whether it should be given for a longer period of time is still open."