Less tamoxifen at a lower dose could make this drug a more palatable preventative.
Prescribing less tamoxifen, and for a shorter duration of time, appears to be just as effective at 10 years from treatment as high doses in preventing breast cancer in high-risk populations, with the benefit of fewer side effects.
The research, published in the Journal of Clinical Oncology, presents the 10 year data for a comparison of treatment outcomes among patients taking tamoxifen for three years at a dose of 5mg/d with those taking a placebo (rather than the standard five years at a dose of 20mg/d).
“We now report that during an extended follow-up period of 10 years, there was a durable reduction in the incidence of breast cancer, mostly invasive,” the authors wrote.
“This result illustrates the carryover benefit of tamoxifen, even at a low dose, up to at least 7 years after treatment cessation, a result that has a meaningful value since it is accompanied by an optimal safety profile.”
The five-year results showed that this dose and period resulted in a halving of the recurrence of hormone-sensitive breast intraepithelial neoplasia without significantly more adverse events than placebo. ASCO and USPSTF guidelines changed to include the lower dose.
“Recent data from US centers show that low-dose tamoxifen is the most popular choice of preventive therapy in women with high-risk lesions, with low discontinuation rates at 1 year compared with the standard dose and other preventive drugs,” the authors wrote.
The study involved 500 women aged 75 and under (mean age 54) with an ECOG score of one or less, who were at increased risk of breast cancer due to having hormone sensitive or unknown breast intraepithelial neoplasia (ADH, DCIS, or LCIS).
The number needed to treat to prevent one case of breast cancer was 22 in 5 years (compared to 218 to produce harm) and 14 in 10 years.
Researchers recorded 25 cases of breast cancer in the tamoxifen arm and 41 in the placebo group, with six contralateral breast cancers in the former and 16 in the latter.
“There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population,” the authors wrote.
The placebo group had 22 serious adverse events, including one pulmonary embolism; the tamoxifen group had 35, including one deep vein thrombosis and one stage I endometrial cancer.
“Notably, menopausal symptoms reported by women were almost the same in the two arms, except for a nearly extra daily hot flash in the tamoxifen arm (the frequency was 1.5-fold higher with tamoxifen compared with placebo). By contrast, tamoxifen at standard doses is associated with at least a doubling of vasomotor symptoms and sexual problems compared with a placebo,” the authors wrote.
Presently, three years is not the standard duration in Australia, and it is difficult to source 5mg or even 10mg tablets, which would make this dosing difficult, said Melbourne surgical oncologist Professor Christobel Saunders.
“But [these results] may well change practice in a few ways,” she said.
“This data confirms the efficacy of tamoxifen in reducing breast cancer events by about 50% in women at high risk due to high-risk lesions, but importantly shows this can be done with a quarter of the conventional dose, that the effect is long-lasting (this has been shown before) and presumably the lower dose leads to fewer side effects,” she said.
“We already often give tamoxifen for DCIS but this may strengthen the recommendation, and lower the dose. We may recommend it more for other lesions, such as ADH, as prevention. We already do this, but there is poor take up. I’m not sure if a low dose will change this― implementation of prevention in cancer is always hard.”