Patients with early-stage breast cancer who are treated with both chemotherapy and tamoxifen have a higher survival rate than patients who receive only tamoxifen. But a combination of tamoxifen and ovarian suppression—treatment to stop the ovaries from functioning—did not show any additional benefits, according to two randomized clinical trials.
Survival rates improve for patients with early-stage breast cancer who receive a single method of treatment—either tamoxifen, ovarian suppression, or chemotherapy. Two international studies by the Adjuvant Breast Cancer Trials Collaborative Group were designed to test whether combining these treatments would provide additional benefits.
Judith Bliss of The Institute of Cancer Research in Sutton, England, and colleagues conducted two randomized controlled phase III clinical trials of 3,854 women with early-stage breast cancer, all of whom were treated with tamoxifen for five years. In the first trial, nearly half of the 2,144 premenopausal women were randomly assigned to receive ovarian suppression, and the other half did not. Some also received chemotherapy. In the second trial, 1,991 patients were randomly assigned to receive chemotherapy, and the other half were not. Some premenopausal women also had ovarian suppression.
The researchers found that chemotherapy treatment resulted in a modest yet sustained improvement in both relapse-free and overall survival. These improvements were especially strong in women younger than 50 years and in premenopausal women who did not receive ovarian suppression.
They also found that neither relapse-free survival nor overall survival was affected by the addition of ovarian suppression. However, the results indicate a possible benefit of ovarian suppression when given along side tamoxifen for a small group of women younger than 40 years who have ER-positive tumors (tumors that need estrogen to grow), especially when they are not receiving chemotherapy. The researchers called for further research into this group of breast cancer patients.
"Relapse-free survival benefits emerged early and were maintained, whereas overall survival benefits did not emerge for at least 5 years, reinforcing the need for long-term follow-up in chemotherapy trials," the authors write. The trials add "to the limited data available on the effects of combining long-term tamoxifen, chemotherapy, and ovarian ablation of suppression."
In an accompanying editorial, Kathleen Pritchard, M.D., of Toronto Sunnybrook Regional Cancer Centre, describes how the trial could have found more interesting results if there had been more data on patients' ER status. "Most of all, however, these studies stress the importance of establishing processes to ensure the availability of archived tumor specimens for all randomized adjuvant trials. The era in which such large important trials should be carried out without the archived correlational tumor samples is over."