Women who take selective estrogen receptor modulators (SERMs) have a 38 percent reduced risk of breast cancer for up to 10 years after diagnosis and treatment, according to the results of a meta-analysis published in The Lancet.
A majority of breast cancers are ER–positive, meaning they are stimulated to grow by the female hormone estrogen. Depriving ER-positive breast cancers of estrogen can slow their growth. Selective estrogen receptor modulators (SERMs) are drugs that block estrogen receptors within the breast cells, thereby reducing estrogen-stimulated growth. Some examples of SERMs include tamoxifen raloxifene, lasofoxifene, and arzoxifene.
Tamoxifen has long been a mainstay of hormonal therapy for breast cancer. It is used for breast cancer treatment as well as for breast cancer prevention in women who are at high risk of the disease. Five years of adjuvant tamoxifen has been shown to reduce the risk of recurrence and death from ER-positive breast cancer and this has been standard treatment for quite some time.
Despite their efficacy, many physicians and patients avoid SERMs because they have been associated with toxic side effects, including an increased risk of blood clots and an increased risk of uterine cancer. However, long-term data is beginning to reveal that the benefits may outweigh the risks.
Researchers conducted a meta-analysis of nine randomized trials in 83,399 women and 306,617 patient-years of follow-up. Collectively, the trials had a median follow-up of 65 months. In most of the studies, the duration of SERM treatment was five years. All patients had a breast cancer risk that ranged between normal and high.
The results of the analysis indicate that overall, SERMs were associated with a 38 percent reduction in the risk of breast cancer at 10 years. The cumulative 10-year incidence of breast cancer was 6.3 percent in control groups and 4.2 percent in SERM groups. The benefit was greater during the first 5 years (42%) than in years 5 to 10 (25%). SERM treatment was associated with a 2.1% incidence of ER-positive breast cancer versus 4% in control groups.
In the breakdown of individual SERMs, tamoxifen showed a 33 percent reduction in breast cancer incidence and raloxifene showed a smaller, but significant benefit (not significantly different from tamoxifen). Lasofoxifene showed a significant reduction in breast cancer at a 0.5 mg dose, but not lower. Arzoxifene was associated with a 58 percent reduction in breast cancer incidence.
All SERMs were associated with a significantly increased risk of thromboembolic events (blood clots); however, were also associated with a 34 percent reduced risk of vertebral fractures.
The researchers concluded that SERMs reduced the incidence of ER-positive breast cancer during treatment and for at least five years after treatment. They recommend careful consideration of the risks and benefits of the drugs.
Cuzick J, Sestak I, Bonanni B, et al. Selective estrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. The Lancet. 2013; 381(9880): 1827-1834.
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