Study results of the Breast International Group (BIG) published Online First in The Lancet Oncology report that aromatase inhibitor letrozole is more effective at preventing breast cancer recurrence in the long term. The 12-year long BIG 1-98 study also reveals that in comparison with tamoxifen, the survival time of women with hormone receptor-positive early breast cancer is significantly improved in the long term.
Meredith Regan from the International Breast Cancer Study Group Statistical Center at the Dana-Farber Cancer Institute in Boston, USA, one of the lead authors on the study explains:
"At a median follow-up of over eight years, women given letrozole monotherapy after surgery for five years had a 20% reduced risk of their breast cancer coming back and were 21% less likely to die compared with women given tamoxifen alone. This updated analysis shows that letrozole offers long-term protection over tamoxifen in these patients."
Approximately 60% of all breast cancers consist of estrogen-receptor positive tumors. Most postmenopausal women with this type of cancer receive aromatase inhibitors (Als) as part of a standard treatment after surgery. At present, letrozole is either administered as a stand-alone treatment or in sequence with tamoxifen.
For the BIG 1-98 trial, researchers assessed a total of 8,010 women who were split into two separate groups for comparison. One group consisting of 4,922 women received 5 years of letrozole with 5 years of tamoxifen whilst the other group of 6,182 women received 5 years of letrozole with sequential treatments of two years of one of these drugs followed by 3 years of the other.
Researchers presented the first results of the trial in 2005 with plans to update the analyses at 2-year intervals considering the persistent and long-term recurrence and death risk in these women.
At the 12-year point after the initial start of the trial researchers reported a 32% increase in the number of relapses compared with the previous ten-year update, i.e. 2,074 recurrences compared with 1,569.
The average follow-up time for long-term patients was 8.1 years. After 5 years the trial revealed that compared with tamoxifen as a monotherapy, patients who received 5 years of daily letrozole monotherapy had a one fifth reduced recurrence and mortality risk.
In the second comparison, i.e. tamoxifen followed by letrozole or vice versa, neither sequential treatment showed a substantial decrease in recurrence or mortality risk compared with letrozole monotherapy.
According to the authors:
"This update of BIG 1-98 at 8.1 years median follow-up reinforces the evidence that letrozole monotherapy is better than tamoxifen in controlling breast cancer recurrence and improving survival for postmenopausal women with endocrine-responsive early breast cancer."
"Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability... overall risk and tradeoffs with respect to side-effects and other burdens will influence the preferred choice of treatment."
Written by Petra Rattue