Breakthrough Study Shows adding Active Tamoxifen Metabolite Boosts Breast Cancer Treatment Effectiveness
STUTTGART, Germany – A new study published in Clinical Cancer Research offers a potential solution for breast cancer patients who don’t respond adequately to standard tamoxifen treatment, a common hormonal therapy. Researchers have found that supplementing tamoxifen with its active metabolite, (Z)-endoxifen, significantly improves treatment effectiveness, particularly in patients with lower levels of a key enzyme needed to activate the drug.
tamoxifen works by blocking estrogen from fueling tumor growth, but requires conversion into (Z)-endoxifen by an enzyme called CYP2D6 to function optimally. Approximately one in three patients have genetically reduced CYP2D6 levels, hindering the drug’s efficacy. While aromatase inhibitors are an choice for postmenopausal women, they aren’t suitable for younger patients, who frequently enough experience higher estrogen levels and, consequently, a greater incidence of certain breast cancers.
The German study, led by Dr. Matthias Schwab at the Dr. margarete fischer-Bosch Institute of Clinical Pharmacology, demonstrated that directly administering (Z)-endoxifen bypasses the need for CYP2D6, restoring hormonal treatment effectiveness.
The research involved 235 women diagnosed with early, hormone-induced breast cancer. Participants received either tamoxifen alone or a combination of tamoxifen and (Z)-endoxifen, based on their individual drug metabolism. Those receiving the combination achieved (Z)-endoxifen blood concentrations comparable to patients who naturally metabolize tamoxifen effectively,suggesting similar treatment benefits.
Importantly, the addition of (Z)-endoxifen was well-tolerated, with reported side effects being mild and similar across both groups.
“Through this approach we offer the first effective solution to a long-standing problem: the insufficient effect of tamoxifen in a notable number of patients,” said Dr. schwab in a statement.
Further research is underway. An interim phase clinical trial testing (Z)-endoxifen in premenopausal women with hormone receptor-positive early breast cancer is currently being conducted in the United States, funded by Atossa Therapeutics. The company anticipates submitting the treatment for review by the US Food and Drug Administration (FDA) in 2026.
