Study of Blood Samples From High-Risk Postmenopausal Women Who Received Treatment on Breast Cancer Prevention Clinical Trials NSABP-P-1 or NSABP-P-2

Study Overview
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Brief Summary
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RATIONALE: Studying the genes expressed in samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. PURPOSE: This research study is looking at blood samples from high-risk postmenopausal women who received treatment on breast cancer prevention clinical trials NSABP-P-1 or NSABP-P-2.

Detailed Description
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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. OUTLINE: Samples are stratified according to CYP2D6 genotype and CYP2D6 metabolizer status. DNA extracted from previously collected blood samples is analyzed in a genome-wide association study and compared with 2 control samples from patients who did not experience a breast event. DNA samples are used to identify and analyze single nucleotide polymorphisms. Also, exploratory analyses are conducted examining the impact of CYP2D6 metabolizer status on breast cancer events according to invasive vs non-invasive disease, ER status, PgR status, histologic type, and TMN stage.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Genetic: DNA analysis
* Genetic: polymorphism analysis
* Other: laboratory biomarker analysis
* Other: pharmacogenomic studies


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Meets 1 of the following criteria: Previously treated on the NSABP-P-1 Breast Cancer Prevention clinical trial Caucasian women that did or did not experience an invasive breast cancer or ductal carcinoma in situ (DCIS) At least 50 years of age at time of entry to P-1 Previously treated on the NSABP-P-2 Breast Cancer Prevention clinical trial Caucasian women that did or did not experience an invasive breast cancer or DCIS Hormone receptor status not specified PATIENT CHARACTERISTICS: Postmenopausal status PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: DNA analysis|nan|
|Genetic: polymorphism analysis|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacogenomic studies|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of genes, as measured by single-nucleotide polymorphisms (SNPs), that are associated with breast events | Retrospective study design: SNPs associated with available breast cancer events | Approximately 6 years | 
| Impact of CYP2D6 metabolizer status on breast cancer events | Retrospective study design: assay results associated with available breast cancer events | Approximately 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploration of whether SNPs within a region are independently associated with a breast event | Retrospective study design: assay results associated with available breast cancer events | Approximately 6 years | 
| Exploration of whether interactions among SNPs increase the risk for a breast event | Retrospective study design: results associated with available breast cancer events | Approximately 6 years | 
| Exploration of whether SNPs have an effect on treatment | Retrospective study design: SNPs associated with appropriate treatment information | Approximately 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ductal breast carcinoma in situ, invasive ductal breast carcinoma, invasive lobular breast carcinoma, invasive lobular breast carcinoma with predominant in situ component