4-hydroxytamoxifen gel strikes out in ductal carcinoma in situ lesions

Local transdermal therapy with 4-hydroxytamoxifen appears to be less effective than full-dose oral tamoxifen in terms of suppressing proliferation in ductal carcinoma in situ (DCIS) lesions for breast cancer prevention, according to a phase II study.

A total of 90 women (mean age 55 years, 58.9 percent White) with oestrogen receptor–positive DCIS lesions were randomly assigned to receive treatment with either oral tamoxifen citrate 20 mg/d plus gel placebo or with 4-hydroxytamoxifen gel 2 mg/d per breast plus oral placebo. Treatment was administered for 4 to 10 weeks, followed by DCIS resection.

Researchers measured the absolute change in DCIS Ki-67 labeling index (Ki67-LI) as the primary endpoint of the study. Secondary endpoints wee 12-gene DCIS Score, breast tissue tamoxifen metabolite concentrations, tamoxifen-responsive plasma protein levels, and patient-reported symptoms.

Of the women included in the study, 15 lacked residual DCIS in the surgical sample, leaving 75 evaluable for the primary endpoint analysis (40 in the oral tamoxifen group and 35 in the 4-hydroxytamoxifen gel group).

Post-treatment Ki67-LI was higher by 3.3 percent (80 percent confidence interval [CI], 2.1–4.6) in the 4-hydroxytamoxifen gel than in the oral tamoxifen group, exceeding the noninferiority margin (2.6 percent).

Furthermore, the DCIS score decreased more with oral tamoxifen than with 4-hydroxytamoxifen gel treatment (−16, 95 percent CI, −22 to −9.4 vs −1.8, 95 percent CI, −5.8 to 2.3).

The oral tamoxifen group had numerically higher 4-hydroxytamoxifen concentrations deep in the breast (median, 5.7 vs 3.8 ng/g) and abundant endoxifen (median, 13.0 vs 0.3 ng/g; p<0.001).

In terms of safety, expected adverse changes in plasma protein levels and vasomotor symptoms occurred in the oral tamoxifen group, with minimal changes in the 4-hydroxytamoxifen gel group.