Switching to letrozole versus continued tamoxifen therapy in treatment of postmenopausal women with early breast cancer.

BACKGROUND: Tamoxifen has been the mainstay of breast cancer therapy. Over time, resistance to tamoxifen may develop. The aromatase inhibitors have proven to be a powerful drug for use in hormone-sensitive early breast cancer. The switching strategy was designed to combine the apparent superior efficacy of aromatase inhibitors with tamoxifen favourable effects.

METHODS: This study was performed on 120 postmenopausal women with histologically confirmed, hormone receptor-positive, operable invasive breast carcinoma who remained free of disease after 2 years of adjuvant tamoxifen therapy. They were randomized to receive either letrozole 2.5mg/day (60 patients) or to continue 20mg/day tamoxifen for 5 years (60 patients).

RESULTS: The treatment groups were well balanced in terms of age, tumor size, nodal status, oestrogen and progesterone receptor status, and previous surgery. The disease recurred in 10 patients in the group receiving tamoxifen and 3 patients in the same group switched to letrozole. There were 8 deaths in the group receiving tamoxifen and 3 deaths in the group of patients who switched to letrozole. Disease-free survival was higher in the group of patients who switched to letrozole compared to the group of patients who received tamoxifen (p=0.04), while the overall survival was not statistically significantly different in the two groups. Letrozole was associated with a significantly lower rate of vaginal bleeding and thromboembolic events. However, bone fractures and adverse cardiovascular events were more frequent in the arm receiving letrozole than in the arm receiving tamoxifen but these differences were not statistically significant.

CONCLUSION: Switching to letrozole after 2 years of tamoxifen may be better than continuing five years of tamoxifen therapy as regard efficacy and tolerability. Further study is recomended on a larger group of patients to verify this finding.

KEY WORDS: Breast cancer - Hormonal treatment - Letrozole - Tamoxifen.