Breast Cancer Research and Treatment

, Volume 106, Issue 3, pp 389–397

A phase II trial of Afimoxifene (4-hydroxytamoxifen gel) for cyclical mastalgia in premenopausal women


    • Department of Surgery, Wales College of MedicineCardiff University
  • Amit Goyal
    • Department of Surgery, Wales College of MedicineCardiff University
  • Elisabeth Le Nestour
    • Besins International
  • Valérie Masini-Etévé
    • Besins International
  • Katharine O’Connell
    • Columbia University Medical Center
  • Afimoxifene (4-OHT) Breast Pain Research Group
Clinical Trial

DOI: 10.1007/s10549-007-9507-x

Cite this article as:
Mansel, R., Goyal, A., Nestour, E.L. et al. Breast Cancer Res Treat (2007) 106: 389. doi:10.1007/s10549-007-9507-x



Many women experience symptoms of cyclical mastalgia, such as breast pain, tenderness, and nodularity. Tamoxifen and other drugs have been used to alleviate cyclical mastalgia symptoms; however, their use is associated with potentially serious side effects. The current study compared the safety and efficacy of two doses of a topical gel containing 4-hydroxytamoxifen (Afimoxifene, formerly known as 4-OHT) with placebo gel for the treatment of moderate to severe cyclical mastalgia.


Premenopausal women aged at least 18 years experiencing moderate to severe symptoms were randomized to receive placebo, 2 mg, or 4 mg of Afimoxifene daily delivered as a transdermal hydroalcoholic gel for 4 menstrual cycles. The primary efficacy parameter was change in mean pain intensity as measured by the Visual Analog Scale (VAS) for the seven worst pain score days within a cycle from baseline to the fourth cycle.


After 4 cycles of treatment, statistically significant improvements relative to placebo were measured in mean VAS score in the 4-mg Afimoxifene group (−12.71 mm [95% confidence interval, −0.96 to −24.47; P = 0.034]). Patient global assessment of pain, physician’s assessment of pain, tenderness on palpation, and nodularity following 4 cycles of treatment were significantly more likely to show improvements in the 4-mg group, compared with placebo (P = 0.010 [pain]; P = 0.012 [tenderness]; P = 0.017 [nodularity]). Overall, Afimoxifene was well tolerated with few adverse events and no drug-related SAE occurred in any group.

There were no changes in menstrual pattern or plasma hormone levels and no breakthrough vaginal bleeding in patients treated with Afimoxifene.


After 4 months of treatment, daily topical breast application of Afimoxifene resulted in statistically significant improvements in signs and symptoms of cyclical mastalgia across patient- and physician-rated scales with excellent tolerability and safety.


4-HydroxytamoxifenAfimoxifeneMastalgiaCyclical mastalgiaBreast tendernessBreast pain

Copyright information

© Springer Science+Business Media, LLC 2007