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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA116201-05
Application #
7890425
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
5
Fiscal Year
2009
Total Cost
$315,533
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Wang, Liewei; Ingle, James; Weinshilboum, Richard (2018) Pharmacogenomic Discovery to Function and Mechanism: Breast Cancer as a Case Study. Clin Pharmacol Ther 103:243-252
Augusto, Bianca M; Lake, Paige; Scherr, Courtney L et al. (2018) From the laboratory to the clinic: sharing BRCA VUS reclassification tools with practicing genetics professionals. J Community Genet 9:209-215
Tu, Xinyi; Kahila, Mohamed M; Zhou, Qin et al. (2018) ATR Inhibition Is a Promising Radiosensitizing Strategy for Triple-Negative Breast Cancer. Mol Cancer Ther 17:2462-2472
Athreya, Arjun P; Gaglio, Alan J; Cairns, Junmei et al. (2018) Machine Learning Helps Identify New Drug Mechanisms in Triple-Negative Breast Cancer. IEEE Trans Nanobioscience 17:251-259
Wiese, Elizabeth K; Hitosugi, Taro (2018) Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect. Front Cell Dev Biol 6:79
Frank, Ryan D; Winham, Stacey J; Vierkant, Robert A et al. (2018) Evaluation of 2 breast cancer risk models in a benign breast disease cohort. Cancer 124:3319-3328
Degnim, Amy C; Winham, Stacey J; Frank, Ryan D et al. (2018) Model for Predicting Breast Cancer Risk in Women With Atypical Hyperplasia. J Clin Oncol 36:1840-1846
Ohmine, Seiga; Salisbury, Jeffrey L; Ingle, James et al. (2018) Aurora-A overexpression is linked to development of aggressive teratomas derived from human iPS cells. Oncol Rep 39:1725-1730
Kourtidis, Antonis; Anastasiadis, Panos Z (2018) Close encounters of the RNAi kind: the silencing life of the adherens junctions. Curr Opin Cell Biol 54:30-36
Leon-Ferre, Roberto A; Polley, Mei-Yin; Liu, Heshan et al. (2018) Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer. Breast Cancer Res Treat 167:89-99

Showing the most recent 10 out of 473 publications