Cancer Risk and Biomarkers of Tamoxifen Chemoprevention
The project is a double blind, randomized, placebo-controlled phase II chemoprevention
The study outcomes will be biological markers, rather than cancer incidence or mortality.
Eligible study subjects will be women, between the ages 25-45, whose calculated lifetime
breast cancer risk is > 20% (25% by the Couch model).
Study participants will be randomly assigned to receive either tamoxifen or placebo for one
year. Participants will subsequently be followed for one year off of medication.
The primary objective is to evaluate the effectiveness of tamoxifen in reducing breast
density by mammogram. Mammographic density has been correlated with breast cancer risk and
reduced breast density may have the added benefit of improving the sensitivity of breast
cancer screening in young women. Breast density will be employed as a marker of
progression-related - proliferative - mechanisms of carcinogenesis.
Secondary study outcomes will include estrogen ratios (catechol estrogen/estradiol), and
markers of oxidative DNA damage in peripheral blood and urine (markers of
progression-related – mutational - events in carcinogenesis). The responsiveness of these
outcomes will suggest the mechanisms through which tamoxifen exerts its preventive effect.
Persistence of the markers after one year of treatment may also provide early information
about the anticipated duration of the tamoxifen effect.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Prevention
Susan Domchek, MD
University of Pennsylvania
United States: Institutional Review Board
|Mayo Clinic||Rochester, Minnesota 55905|
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|University of Pennsylvania||Philadelphia, Pennsylvania 19104|
|Wayne State University||Detroit, Michigan 48202|
|UCLA Medical Center||Los Angeles, California 90095-7059|
|Dana Farber Cancer Institute||Boston, Massachusetts 02115|