Low-Dose Endoxifen Reduces Breast Density with Fewer Side Effects, Study Finds
A new study from Karolinska Institutet, published in the Journal of the National Cancer Institute, reveals that low doses of the drug endoxifen can reduce breast density as effectively as the standard treatment tamoxifen, while causing significantly fewer side effects.
Study Design and Key Results
The proof-of-concept trial involved 240 healthy, premenopausal women who were randomly assigned to receive either a placebo, 1 mg of endoxifen, or 2 mg of endoxifen daily for six months. Mammographic breast density—a key indicator of breast cancer risk—was measured before and after treatment.
"Both 1 and 2 milligrams of endoxifen resulted in a clear reduction in breast density compared with the placebo."
— Mattias Hammarström, co-author and PhD candidate, Karolinska Institutet
Efficacy and Side Effects
The results showed that:
- 1 mg endoxifen reduced breast density by an average of 19%
- 2 mg endoxifen reduced breast density by an average of 26%
- By comparison, the standard 20 mg dose of tamoxifen reduced density by approximately 18.5% in a previous study.
Importantly, the lower dose was better tolerated. Participants taking 2 mg reported more severe hot flushes and night sweats. In contrast, the 1 mg group had a safety profile similar to placebo in terms of serious side effects and biomarkers.
"Our results suggest that a lower dose may be sufficient to affect breast density, whilst also appearing to be better tolerated."
— Mattias Hammarström
What This Means
This study is a proof-of-concept trial, designed to demonstrate a biological effect before moving to larger, longer-term studies. It does not directly show whether endoxifen reduces breast cancer risk or recurrence. However, the findings offer a promising pathway toward a treatment that could be as effective as tamoxifen but with a significantly lower burden of side effects.