Aromatase Inhibitors, Breast Density and Plasma Steroid Hormones

Understanding variability in the response to breast cancer therapy is important so that the most effective therapy can be administered to patients in a timely manner. Aromatase inhibitors (Als) have attained a prominent place in the management of postmenopausal women with hormone receptor positive breast cancer, but there are limited data on interindividual variability in responses to this therapy. In Project 4 of the Mayo Breast SPORE we propose to advance our translational research goal of identifying potentially significant responses to Al therapy via changes in plasma steroid hormone levels, changes in mammographic breast density and plasma drug concentrations as well as understanding the genetic influence on these responses to Al therapy. The specific aims of the study are 1) To evaluate changes in percent and area mammographic density in response to Al therapy from pre-treatment to one-year of therapy, 2a) To describe the changes in select plasma steroid hormones (that are either substrates or products of the aromatase activity) from pre-treatment to one year on Al therapy, and correlate with changes in percent and area density over the same time period and, 2b) To describe the variation in plasma anastrozole or exemestane concentrations at one year of Al therapy and correlate with changes in percent and area mammographic density from pre-treatment to one-year. Secondary Aims will examine haplotype tagged SNPs in genes in the cytochrome P450 enzyme system identified through the Mayo Clinic and Indiana University Pharmacogenomics Research Network Projects with changes in percent and area density, changes in hormone levels and drug concentrations. The Primary and Secondary aims will be investigated within an ancillary study to an NCIC CTG clinical trial of aromatase inhibitors, MA27D. Pretreatment and one-year blood samples, mammograms and questionnaire data will be collected. Aim 2 will also be examined in an ethnically diverse population of 200 women receiving Al therapy (anastrozole) as standard of care at the Mayo Clinic or MD Anderson Cancer Center. Predicting the response to Al therapy via mammographic breast density, steroid hormone levels and genetic variation has the potential for timely identification of women who will not respond to therapy and for whom alternative treatments can be administered.