Study Compares Tamoxifen Gel Applied to the Breast With Oral Tamoxifen in Women With DCIS


Key Points

  • A randomized phase II study comparing transdermal 4-OHT gel vs oral tamoxifen in women with DCIS has found the gel to be as effective in reducing cell proliferation as the oral formulation, with fewer side effects.
  • The substantial reduction in blood 4-OHT levels in the gel arm correlated with a reduction in factors that cause blood clots.
  • Providing women at high risk for breast cancer and those with DCIS with an alternative to oral tamoxifen may encourage more women to adhere to preventive therapy.

A randomized, double-blind, placebo-controlled phase II trial comparing the antiproliferative effect of transdermal 4-hydroxytamoxifen gel (4-OHT), a potent antiestrogenic metabolite of tamoxifen, applied to the breast and oral tamoxifen in women with ductal carcinoma in situ (DCIS), has found the gel therapy was as effective in reducing cell proliferation as the oral formulation. In addition, hormonal and blood clotting side effects with the gel version were fewer than with oral tamoxifen. The study by Lee et al was published in Clinical Cancer Research.

Study Methodology

The researchers randomly assigned 26 women between the ages of 45 and 86 with estrogen receptor–positive DCIS to receive either 4-OHT gel (4 mg/d, 2 mg to each breast) or oral tamoxifen  (20 mg/d). The women provided a baseline blood sample and completed the Breast Cancer Prevention Trial Eight Symptom Scale (BESS) questionnaire. Participants on the gel arm were instructed to apply the gel to the entire skin envelope of each breast each morning after a shower. The duration of the therapy was 6 to 10 weeks.

All participants provided a second blood sample at the end of the study and completed the BESS questionnaire at 15 days, at the end of the study, and during the postsurgery visit.


The researchers found that after 6 to 10 weeks of gel application, the reduction in Ki-67, a marker of cell proliferation, in breast tissue was comparable with that of oral tamoxifen taken for a similar period of time. Although there were equal amounts of 4-OHT present in the breast tissue of patients from both the gel and oral tamoxifen arms collected during surgery (5.8 ng/g vs 5.4 ng/g, respectively), the levels of 4-OHT in the blood of patients from the gel arm was 5.5-fold lower than it was in the blood of those from the oral tamoxifen arm (0.2 ng/mL vs 1.1 ng/mL, respectively).

The substantial reduction in the levels of 4-OHT in the blood of patients in the gel arm correlated with a reduction in factors that cause blood clots. However, the patients had no significant improvement in vaginal symptoms, gastrointestinal symptoms, or hot flashes compared with the patients in the oral tamoxifen arm of the study.

“Our data support the notion that local transdermal drug delivery to the breast will achieve sufficient drug concentrations to be effective, with low systemic exposure,” concluded the study authors. “This concept deserves further testing with 4-OHT, and is likely to be applicable to other lipophilic drugs with low molecular weight.”

Seema A. Khan, MD, of Northwestern University Feinberg School of Medicine, Chicago, is the corresponding author for the Clinical Cancer Research article.

The study was funded by the National Institutes of Health and PHR Pharma LLC. The study authors reported no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.