KARISMA results: Low dose of tamoxifen have a potential treatment effect

The results from the 6-armed RCT trial KARISMA 2 show that 2.5 mg of tamoxifen has the potential to be as effective in reducing incidence and recurrence of breast cancer as the established 20 mg dose. 

Mammographic density change is a proxy for tamoxifen therapy response. We tested if lower doses of tamoxifen were non-inferior to reduce mammographic density and associated with fewer symptoms.

In all 1440 women, aged 40 to 74 years, participating in the Swedish mammography screening program were included in the six-months double-blind six-arm randomized placebo-controlled KARISMA phase II trial and randomized to either placebo, 1, 2.5, 5, 10 and 20 mg of tamoxifen.

The participants had non-inferior mammographic density reduction following 2.5, 5, and 10 mg tamoxifen compared with the median 10.1% decrease observed in the 20 mg group. The reduction was confined to premenopausal women. Severe vasomotor symptoms (hot flashes, cold and night sweats) were reduced by approximately 50% in the 2.5, 5, and 10 mg groups compared with the 20 mg group.

In conclusion,  premenopausal women showed non-inferior magnitude of breast density decrease at 2.5 mg of tamoxifen and experienced fewer side effects compared to the standard dose of 20 mg.

Future studies should test if 2.5 mg of tamoxifen reduces the risk of primary breast cancer.

Eriksson, et al J Clin Oncol. 2021 Mar 18:JCO2002598. doi: 10.1200/JCO.20.02598.