Changes in Breast Density and Plasma Hormone Levels After One Year of Aromatase Inhibitor Therapy

OBJECTIVES:

• To assess the changes in percent breast density (in response to 1 year of aromatase inhibitor therapy) from levels prior to the initiation of treatment.
• To assess the changes in dense area (in response to 1 year of aromatase inhibitor therapy) from levels prior to the initiation of treatment.
• To examine whether changes in percent breast density (in response to 1 year of aromatase inhibitor therapy) from pre-treatment levels correlate with changes in plasma hormone levels (estrone, estrone-sulfate, estradiol, and SHBG) and drug levels (anastrozole or exemestane) over the same time period.
• To examine whether changes in dense area (in response to 1 year of aromatase inhibitor therapy) from pre-treatment mammogram correlate with changes in plasma hormone levels (estrone, estrone-sulfate, estradiol, and SHBG) and drug levels (anastrozole or exemestane) over the same time period.
• To assess whether women with high pre-treatment percent density (upper tertile) experience greater decreases in percent breast density after 1 year of aromatase inhibitor therapy than women with low pre-treatment percent density (lower tertile).
• To assess whether women with high pre-treatment dense area (upper tertile) experience greater decreases in dense area after 1 year of aromatase inhibitor therapy than women with low pre-treatment dense area (lower tertile).
• To examine the associations of haplotype-tagged single nucleotide polymorphisms in genes in the aromatase pathway identified through the Mayo Clinic and Indiana University Pharmacogenomics Research Network Projects, with changes in percent and area density, plasma hormone levels, and drug levels after 1 year of aromatase inhibitor therapy.

OUTLINE: This is a multicenter study.

Patients undergo blood sample collection at baseline and at 1 year after initiation of aromatase inhibitor therapy (anastrozole or exemestane). Samples are analyzed for estrogen and testosterone levels and additional hormone levels and growth factors that have been previously linked with breast density and that could be altered by aromatase inhibitor use (i.e., sex hormone-binding globulin [SHBG], DHEA, DHEA sulfate, progesterone, prolactin, insulin-like growth factor-1 [IGF-1], and insulin-like growth factor binding protein 3 [IGF BP3]). Samples are also analyzed for anastrozole and exemestane levels by HPLC. Pharmacogenetic studies are also performed. Haplotype-tagged single nucleotide polymorphisms in genes in the aromatase pathway are examined.

Patients also undergo mammogram at baseline (≤ 6 months prior to study registration) and at 1 year after initiation of aromatase inhibitor therapy.