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Topical tamoxifen noninferior to oral formulation for breast cancer

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July 25, 2014

A topical formulation of tamoxifen demonstrated an equally effective antiproliferative effect as oral tamoxifen in women with ductal carcinoma in situ of the breast. Topical tamoxifen also was associated with reduced effects on endocrine and coagulation parameters, according to recent findings.

“Oral tamoxifen is used by some women at high risk for breast cancer to prevent the development of the disease, and our data suggest that gel application of tamoxifen could replace this approach, thus encouraging more women to adhere to preventive therapy,” researcher Seema A. Khan, MD, professor of surgery at Northwestern University Feinberg School of Medicine, said in a press release.

Seema Khan, MD

Seema A. Khan

To compare the efficacy of oral tamoxifen vs. topical tamoxifen gel, Khan and colleagues evaluated 26 pre- and postmenopausal women aged 45 to 86 years with newly diagnosed ER-positive ductal carcinoma in situ (DCIS).

At baseline, the researchers collected serum samples from all patients who completed the Breast Cancer Prevention Trial Eight Symptom Scale questionnaire.

Patients were randomly assigned to 1 mL transdermal 4-hydroxytamoxifen (4-OHT) gel plus placebo daily or 20 mg oral tamoxifen daily with gel placebo, with treatments continuing for 6 to 10 weeks before surgery.

The researchers used liquid chromatography/tandem mass spectrometry to measure plasma, nipple aspirate tissue and breast adipose tissue levels of tamoxifen and its metabolites.

They defined the study’s primary endpoint as Ki67 labeling in DCIS lesions as evaluated by immunohistochemistry. Plasma levels of insulin-like growth factor I (IGF-I), sex hormone-binding globulin (SHBG) and coagulation protein were ascertained.

According to study results, Ki67 was reduced by 3.4% in the 4-OHT group and by 5.1% in the oral-T group (P≤ .03 in both; between-group P=.99).

Researchers observed mean concentrations of 4-OHT in breast adipose tissue were 5.8 ng/g in the 4-OHT group and 5.4 ng/g in patients treated with oral tamoxifen (P=.88). Mean plasma concentrations were 0.2 ng/mL in the 4-OHT group and 1.1 ng/mL in the oral tamoxifen group (P=.0003).

In the oral tamoxifen group, significant increases were seen in SHBG, Factor VIII and von Willebrand’s factor, as well as a significant decrease in plasma IGF-I. These changes did not occur in the 4-OHT group. The occurrence of hot flashes was comparable between the groups.

The researchers also noted that gel administration of 4-OHT may circumvent the potentially harmful effects of liver metabolism of tamoxifen.

“Tamoxifen has to be broken down by the liver to its active components, which include 4-OHT. In this process, harmful side effects can also arise, such as the activation of proteins that cause blood clots,” Khan said in a press release. “Because the liver metabolism step is eliminated when the 4-OHT gel is directly applied to breast skin, the harmful effect of increasing the risk for blood clots should also be eliminated.”

Disclosure: The researchers report no relevant financial disclosures.

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