Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Afimoxifene

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Patients apply placebo gel topically to each breast QD for up to 52 weeks.

Patients apply afimoxifene gel topically to each breast QD for up to 52 weeks.

Laboratory Biomarker Analysis

Placebo

Questionnaire Administration

Banu Arun, MD

This randomized phase II trial studies how well afimoxifene works in reducing the risk of breast cancer in women with mammographically dense breast. Estrogen can cause the growth of breast cancer cells. Hormone therapy using afimoxifene may fight breast cancer by blocking the use of estrogen by the tumor cells.

PRIMARY OBJECTIVES:

I. To estimate and compare the percent change in mammographic breast density (using Cumulus software) from baseline to month 12 in women applying 4mg afimoxifene (4-hydroxytamoxifen \[4-OHT\]) gel per breast versus placebo.

SECONDARY OBJECTIVES:

I. To compare the Cumulus versus (vs.) Volpara breast density measurement methods to estimate percent change in mammographic breast density from baseline to month 12 in women applying 4mg of 4-OHT gel per breast vs. placebo.

II. To compare the percentage of women who underwent a change in Breast Imaging Reporting and Data System (BIRADS) category, comparing pre-and post- treatment measurements, for recipients of active agent versus placebo.

III. To estimate percentage of women with \>= 10% absolute decrease in quantitative mammographic density percentage between baseline and 12 months, comparing between treated group 4mg per breast 4-OHT gel to placebo.

IV. To describe symptoms assessed by breast cancer prevention trial (BCPT) eight symptom scale (BESS) questionnaire and laboratory toxicity assessment (factor VIII \[F VIII\], Von Willebrand \[vWB\] factor, sex hormone-binding globulin \[SHBG\], lipid profile).

V. To evaluate serum measurements of 4-OHT and related metabolite levels and factors related to tamoxifen exposures, such as insulin-like growth factor (IGF) pathway members, C-reactive protein (CRP), estradiol.

VI. To evaluate tissue biomarkers (among women undergoing optional pre- and post-treatment biopsies): terminal duct lobular unit (TDLU) involution; collagen structural changes; SETER/PR index: estrogen related transcription, Ki-67, COX-2, p16, CD68.

VII. To examine whether any reductions in mammographic density seen after 1 year of 4-OHT vs. placebo gel application persist at 24 months, one year after gel application has stopped.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients apply placebo gel topically to each breast once daily (QD) for up to 52 weeks.

ARM B: Patients apply afimoxifene gel topically to each breast QD for up to 52 weeks.

After completion of study treatment, patients are followed up at 24 months.

Afimoxifene in Reducing the Risk of Breast Cancer in Women With Mammographically Dense Breast

A Randomized, Double-Blind, Placebo-Controlled Study of 4-hydroxytamoxifen Topical Gel in Women With Mammographically Dense Breast

To determine change of mammographic breast density using Cumulus software. Cumulus is a semi-automated computerized measure of dense area that uses reader-based thresholds to define the breast edge and regions of density on a digital or digitized mammogram. Each pixel within the breast area between the skin line and pectoral muscle is segmented into either fat or fibro glandular tissue; this defines the cut-off point.

To determine change of mammographic breast density using Volpara software. Volpara software uses a combination of x-ray physics and machine learning to generate an accurate volumetric measure of breast composition.

To evaluate plasma measurements of 4-OHT levels, Z-4-OH-Tamoxifen.

To evaluate tissue measurements of 4-OHT levels, Z-4-OH-Tamoxifen

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Participants apply 4-OHT Gel topically to each breast QD for up to 52 weeks.

4-OHT Gel: Applied topically

4-OHT Gel

Participants apply Placebo gel topically to each breast QD for up to 52 weeks.

Placebo: Applied topically

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Banu Arun

Craniocaudal View (CC view)

Mediolateral Oblique View (MLO view)

Mammographic breast density data are available in a total of 133 participants, two without baseline data, six without month-12 data and two with 12-month mammograms beyond 18 months therefore are not considered evaluable for Month 12 evaluation. Therefore, a total of 123 participants are evaluable for the primary endpoint, 61 in 4-OHT and 62 in Placebo.

Mammographic Breast Density Using Cumulus Software

A total of 59 participants have been evaluated for breast density at either baseline or month 12 or both by Volpara data, however 23 in 4-OHT and 24 in Placebo by CC view, and 25 in 4-OHT and 24 in Placebo by MLO view are evaluable for percent change in mammographic breast density.

Mammographic Breast Density Using Volpara Software

Below Qualification Limit (BQL) at 12 months

Greater than BQL at 12 months

A total of 59 and 57 participants in 4-OHT and Placebo arms, respectively, have Month 12 measures on 4-OHT in plasma. All baseline measures are Below Qualification Limit (BQL).

4-OHT Plasma Levels

Below Qualification Limit (BQL)

Greater than BQL

A total of 12 and 18 participants in 4-OHT and Placebo arms, respectively, have Month 12 measures on 4-OHT in tissue. All baseline measures are Below Qualification Limit (BQL).

Spots Global Cancer Trial Database for mammographically dense breast