Postoperative adjuvant therapy with tamoxifen, tegafur-uracil (UFT), or both in women with node-negative breast cancer: A pooled analysis of six randomized controlled trials (relapse-free survival data)

633 Background: In Japan, 6 randomized controlled trials of the oral 5-fluorouracil derivative tegafur-uracil (UFT) and tamoxifen (TAM), given alone or in combination, have been simultaneously performed in women with node-negative breast cancer. We performed a pooled analysis, based on the intention to treat, of individual patient data from these 6 trials (involving 2934 patients). Data on overall survival, the primary endpoint, have been reported previously (Noguchi et al., Journal of Clinical Oncology, 2005). We now report data on relapse-free survival (median follow-up, 6.2 years). Methods: Three 3-arm randomized controlled trials (surgery alone vs. surgery plus TAM vs. surgery plus UFT) and three 4-arm randomized controlled trials (surgery alone vs. surgery plus TAM vs. surgery plus UFT vs. surgery plus TAM and UFT) were performed in women with node-negative breast cancer. The results underwent a pooled analysis. Results: The 5-year relapse-free survival rate was 87.9% with surgery alone (n = 860; risk ratio [RR], 1), 90.5% with surgery plus TAM (n = 865; RR, 0.81; confidential interval [CI], 0.60–1.11; P = 0.21), 89.9% with surgery plus UFT (n = 860; RR, 0.83; CI, 0.66–1.21; P = 0.46), and 92.7% with surgery plus UFT and TAM (n = 349; RR, 0.63; CI, 0.39–0.99; P = 0.046). Subset analysis showed that combination therapy with UFT and TAM was not effective for women with estrogen-receptor-negative breast cancer (RR, 0.90; CI, 0.46–1.75; P = 0.75), but was very effective for women with estrogen-receptor-positive breast cancer (RR, 0.39; CI, 0.19–0.79; P = 0.009). Conclusions: Our results suggest that the effectiveness of oral fluoropyrimidine derivatives is enhanced by concurrent treatment with TAM in women with node-negative breast cancer. This contrasts with the results of previous studies showing that the response to anthracycline-based chemotherapy is attenuated in patients concurrently receiving TAM. No significant financial relationships to disclose.