Five Years of Tamoxifen Superior to 2-3 Years

ASCO--Data from a large multi-center European study has confirmed thesuperiority of five years of tamoxifen (Nolvadex) therapy as opposed totwo or three years in postmenopausal breast cancer patients. When longerfollow-up data are available, the trial will be able to determine whethereven longer duration of tamoxifen (12 to 13 years) might provide additonalbenefits.

The findings confirm those of a smaller Scottish study reported at theASCO meeting last year, as well as the findings of other studies in theliterature.

This study involved almost 3,800 postmenopausal early breast cancerpatients, each of whom had taken tamoxifen for two to three years priorto enrollment in the trial.

The rationale of the trial was based on clinical results as they wereknown in 1985 when the trial was organized. "Adjuvant tamoxifen isknown to result in a significant reduction in the odds of recurrence andmortality in early breast cancer. However, the optimal duration has notbeen determined and remains controversial," said Dr. Thierry Delozier,of the Centre François Baclesse, Caen, France, in his presentationof the data at the ASCO integrated session on breast cancer.

At randomization, half the patients stopped taking tamoxifen and halfcontinued treatment. The trial was conducted between September 1986 andMay 1995.

Because so few events had occurred at 10 years, the protocol was modifiedin 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 oftherapy 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 numberwas positive for estrogen receptors. About 30% of patients received adjuvantchemotherapy. Tamoxifen dosage ranged from 10 to 70 mg daily. The majorityof patients received 20 to 40 mg daily.

Median follow-up in the trial has reached 48 to 49 months for both patientgroups. The mean duration of tamoxifen therapy was 30 months in patientswho discontinued therapy at randomization and 70 months in the patientswho 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 oftamoxifen therapy significantly improved five-year disease-free survival,80% versus 72% (P = .002).

The incidence of endometrial cancer was virtually identical in the twogroups, as 13 patients developed the cancer in the short-term tamoxifengroup versus 12 in the long-term cohort. Contralateral breast cancer occurredmore often in the short-term therapy group, 44 cases versus 27 in patientswho continued treatment.

Analysis of the data by different dosages showed an advantage for thelong-term therapy group at 30 mg daily but not for 20 mg or 40 mg, themost common doses.

Disease-free survival had an unexpected association with nodal status.Long-term therapy benefited patients who had positive lymph nodes but notthose with negative nodes. Dr. Delozier had no explanation for the finding.

The results leave unanswered the question of optimal duration of tamoxifentherapy. "We need further follow-up to assess the value of longerduration of therapy with tamoxifen," he said. "I think the onlyrecommendation we can make at this point is that tamoxifen should be givenfor at least five years, but the question of whether it should be givenfor a longer period of time is still open."