Beyond tamoxifen: Extended and late extended endocrine therapy in postmenopausal early breast cancer

SummaryBreast cancer is a leading cause of cancer death among women worldwide. The majority of cases are oestrogen receptor- or progesterone receptor-positive and, therefore, potentially sensitive to endocrine therapy. A significant risk of recurrence and death persists following initial diagnosis, with over one half of all recurrences and two thirds of breast cancer-related deaths reported to occur following completion of standard adjuvant tamoxifen therapy. There is a need for effective protection against recurrence beyond the initial 5 years of adjuvant treatment for women with hormone-responsive cancer. Extended adjuvant endocrine therapy with letrozole following completion of adjuvant tamoxifen treatment is well tolerated and reduces recurrence risk by 42% and the risk of developing distant metastases by 40% when compared with placebo. Extended adjuvant letrozole therapy confers protection against late relapses and should be considered for women completing adjuvant tamoxifen therapy. The MA.17 trial was unblinded early because of a statistically significant benefit in disease-free survival with letrozole, and patients receiving placebo were allowed to receive letrozole. MA.17 post-unblinding results show that women originally randomised to placebo who then chose to receive letrozole at the time of trial unblinding experienced a significant improvement in all outcomes (disease-free survival and distant disease-free survival), including a significant survival advantage when compared with women in the placebo arm who chose to continue with no further treatment. Physicians should consider late extended adjuvant therapy for women who have been off tamoxifen for some time, as it may offer benefit in outcomes, and this option should be discussed.