NCI-supported Breast Cancer De-escalation Trial Exceeds Accrual Expectations

An NCI-supported phase 3 clinical trial (LoTam; A012301) is comparing the effect of low-dose tamoxifen to usual hormonal therapy in the treatment of post-menopausal women with low-risk, early-stage breast cancer. The goal is to evaluate whether the recurrence-free interval (RFI) with low-dose tamoxifen is no worse than standard-of-care hormone therapy among this subset of women.

A unique clinical trial approach

Usually, post-menopausal women whose tumors have the molecular characteristics of invasive, early-stage breast cancer (estrogen receptor positive/HER-2-negative) would be treated with the standard of care hormone therapy that includes: 
1.) an antiestrogen such as tamoxifen to prevent estrogen action in the tumor
2.) an aromatase inhibitor to prevent the formation of endogenous estradiol before it can exert its negative effects.

However, LoTam is testing de-escalation of treatment: whether low-dose tamoxifen may be enough to treat this specific subset of women with breast cancer. The de-escalation focus of treatment could show that a lower dose of tamoxifen is as effective as the commonly used dose while offering the benefit of less severe toxicity. NCI is uniquely situated to support de-escalation trials, which are not typically run in the private sector.

LoTam exceeded its accrual goals

Although the trial opened in 2025 with a 4.8-year accrual target, LoTam reached its initial targeted accrual in just one year. LoTam was temporarily closed to accrual in early 2026 to accommodate the high accrual rate and was reactivated in April to include more patients.

The exceptional accrual rate may provide evidence for the public’s interest in de-escalation studies.