The Pharmacogenomics of Breast Cancer Prevention: A Genome-Wide Association Study in Participants Experiencing Breast Cancer Events in High-Risk Postmenopausal Women Receiving Selective Estrogen Receptor Modulators on NSABP Trials P-1 and P-2

OBJECTIVES:

Primary

• To identify genes associated with breast events (i.e., the occurrence of invasive breast cancer or ductal carcinoma in situ), in terms of single-nucleotide polymorphisms (SNPs) in a genome-wide association study, in Caucasian women at high risk of developing breast cancer who have received a selective estrogen receptor modulator (SERM) (i.e., tamoxifen or raloxifene) on the NSABP-P-1 OR NSABP-P-2 breast cancer prevention clinical trials.
• To determine the impact of CYP2D6 metabolizer status, which includes genotype and status of concurrent use of CYP2D6 inhibitors, on breast cancer events in participants receiving either tamoxifen or raloxifene.

Secondary

• To explore whether multiple SNPs within a region are independently associated with a breast event.
• To explore whether there are interactions among SNPs that increase the risk for a breast event.
• To explore whether there is interaction of any SNPs identified in the primary objective with randomized treatment, in terms of the risk for a breast event.
• To identify rare variants that might affect estrogen-dependent expression of chromosomes (CTSO) 4 and 16 (ZNF423) and/or the relationship to BRCA1 expression.