This phase II trial studies how well topical afimoxifene works in treating patients with breast cancer who have undergone radiation therapy on one breast. Topical afimoxifene is a quick-drying medicated gel that may block the growth of breast cancer cells when applied to the breast skin. The purpose of this research is to determine what effect, if any, differences in skin type between women have on the delivery of topical afimoxifene to the breast tissue, and whether radiation affects the delivery of topical afimoxifene to breast tissue.
PRIMARY OBJECTIVES: I. To identify the skin features that drive inter-individual variation in dermal drug permeation between individuals. SECONDARY OBJECTIVES: I. To relate breast tissue drug concentration to skin histology, skin vascularity, skin transporter proteins, and skin features measured using confocal reflectance microscopy. II. To assess the feasibility of transdermal drug delivery to the radiated breast. OUTLINE: Patients apply afimoxifene gel topically once daily (QD) to both breasts for 4 weeks and then undergo core needle biopsies of both breasts. Patients receive follow up phone call 21-35 days after biopsy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
156
Northwestern University
Chicago, Illinois, United States
University of Illinois Cancer Center
Chicago, Illinois, United States
Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin histology, blood and lymph vessel density
Univariate analyses will relate each characteristic to tissue drug concentration using either correlation analysis for continuous characteristics or a t-test, analysis of variance or rank sum test for categorical characteristics. Multiple linear regression modelling will be used to select those characteristics that provide the strongest independent contribution to the model.
Time frame: Up to 35 days post-treatment
Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to the expression of xenobiotic transporters and enzymes
Univariate analyses will relate each characteristic to tissue drug concentration using either correlation analysis for continuous characteristics or a t-test, analysis of variance or rank sum test for categorical characteristics. Multiple linear regression modelling will be used to select those characteristics that provide the strongest independent contribution to the model.
Time frame: Up to 35 days post-treatment
Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin features
Will be measured with confocal reflectance microscopy. Univariate analyses will relate each characteristic to tissue drug concentration using either correlation analysis for continuous characteristics or a t-test, analysis of variance or rank sum test for categorical characteristics. Multiple linear regression modelling will be used to select those characteristics that provide the strongest independent contribution to the model. A similar analysis will be conducted using the skin characteristics from the confocal reflectance microscopy.
Time frame: Up to 35 days pot-treatment
Effect of breast radiotherapy on drug concentrations resulting from transdermal delivery of afimoxifene (4-OHT)
Tissue drug concentrations will be compared between radiated and non-radiated breasts using a mixed linear model, with breast radiation status as a fixed effect of interest and person as a random effect. Analyses will also be done to compare the skin data (histology, immunohistochemistry \[IHC\], protein expression, CRS) between radiated and non-radiated breasts. While most characteristics will be continuous, other metrics will be analyzed by using different link functions in similarly constructed generalized linear model.
Time frame: Up to 35 days post-treatment
Differences between radiated and non-radiated skin and breast tissue that contribute to differences in permeation
Tissue drug concentrations will be compared between radiated and non-radiated breasts using a mixed linear model, with breast radiation status as a fixed effect of interest and person as a random effect. Analyses will also be done to compare the skin data (histology, IHC, protein expression, CRS) between radiated and non-radiated breasts. While most characteristics will be continuous, other metrics will be analyzed by using different link functions in similarly constructed generalized linear model.
Time frame: Up to 35 days post-treatment
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