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

May 6, 2015 updated by: NSABP Foundation Inc

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

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.

Study Overview

Status

Unknown

Conditions

Breast Cancer

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

1881

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

breast cancer cases and matched controls from: participants in NSABP P-1 (tamoxifen or no tamoxifen) participants in NSABP P-2 (raloxifene or no raloxifene; tamoxifen or no tamoxifen)

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Case-Control
Time Perspectives: Retrospective

What is the study measuring?

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 Time Frame: Approximately 6 years	Retrospective study design: SNPs associated with available breast cancer events	Approximately 6 years
Impact of CYP2D6 metabolizer status on breast cancer events Time Frame: Approximately 6 years	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 Time Frame: Approximately 6 years	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 Time Frame: Approximately 6 years	Retrospective study design: results associated with available breast cancer events	Approximately 6 years
Exploration of whether SNPs have an effect on treatment Time Frame: Approximately 6 years	Retrospective study design: SNPs associated with appropriate treatment information	Approximately 6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NSABP Foundation Inc

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Goetz MP, Schaid DJ, Wickerham DL, Safgren S, Mushiroda T, Kubo M, Batzler A, Costantino JP, Vogel VG, Paik S, Carlson EE, Flockhart DA, Wolmark N, Nakamura Y, Weinshilboum RM, Ingle JN, Ames MM. Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical trials. Clin Cancer Res. 2011 Nov 1;17(21):6944-51. doi: 10.1158/1078-0432.CCR-11-0860. Epub 2011 Aug 31. Erratum In: Clin Cancer Res. 2012 Jun 15;18(12):3491.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Anticipated)

December 1, 2015

Study Completion

December 7, 2022

Study Registration Dates

First Submitted

August 26, 2009

First Submitted That Met QC Criteria