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Study Description

The primary aim of this study is to identify genes related to the occurrence of breast events, defined as occurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), in women at high risk of developing breast cancer who have received a Selective Estrogen Receptor Modulator (SERM - tamoxifen or raloxifene) on the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 or P-2 trials. Cases and controls were selected from the tamoxifen arm in the P-1 and from the tamixifen and raloxifene arms in the P-2 trial. For the P-1 trial, cases and controls were required to be 50 years of age or older at time of entry. Cases were females who experienced an invasive breast cancer or DCIS on P-1 or P-2. Controls were females who did not experience an invasive breast cancer or DCIS.

A nested matched case-control design was used, with matching on the following factors: 1) trial and treatment arm (P-1 tamoxifen, P-2 tamoxifen, P-2 raloxifene); 2) age at trial entry (when controls could not be exactly matched on age, we incremented the age of matching by +/- 1 year, in sequence until a match was obtained without exceeding +/- 5 years); 5-year predicted breast cancer risk based on the Gail model ( <2.00%, 2.01-3.00, 3.01-5.00, >5.01), 3) history of lobular carcinoma in situ (yes vs. no); 4) history of atypical hyperplasia in breast (yes vs. no); 5) time on study (controls must be on study at least as long as the time to diagnosis of the breast event for the case). Because 94.2% of the participants on P-1 and P-2 treated with tamoxifen or raloxifene were Caucasian, this study was restricted to only Caucasians.

Two cases and two controls were randomly chosen as duplicates for quality control of genotype concordance. The DNA samples were plated into 96-well plates, with cases and controls randomly distributed across the plates. A Caucasian parent-child CEPH trio from the HapMap project was included to check for Mendelian transmission of alleles. Genotypes were determined by the RIKEN Center for Genomic Medicine with the Illumina Human610-Quad.

  • Study Type: Nested Case-Control
  • Number of study subjects that have individual level data available through Authorized Access: 1763

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

Women enrolled on the NSABP breast cancer prevention trials P1 and P2 were potentially eligible for this GWA study. To avoid population confounding, analyses were restricted to Caucasian, and those who provided consent for use of their samples.

Breast cancer cases enrolled met the following definition: a female, receiving tamoxifen, who experienced an invasive breast cancer or DCIS on P-1, provided she was 50 years of age or older at time of entry to P-1, or a female who experienced an invasive breast cancer or DCIS on P-2 (all of whom received either tamoxifen or raloxifene). Controls enrolled met the following definition: a female, receiving tamoxifen entered on P-1, provided she was 50 years of age or older at time of entry to P-1, who did not experience an invasive breast cancer or DCIS, or a female entered on P-2 (all of whom received either tamoxifen or raloxifene) who has not experienced an invasive breast cancer or DCIS. Controls were matched to cases on the following factors:Trial arm, Age, 5-year predicted breast cancer risk, History of lobular carcinoma in situ, History of atypical hyperplasia in breast, time on study.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina Human610_Quadv1_B 601273 1048904
Study History

March 17, 2009: Protocol approved by the Cancer Prevention and Control Protocol Review Committee, Division of Cancer Prevention, Community Oncology and Prevention Trials Research Group, National Cancer Institute.

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Other NCBI Resources
Authorized Data Access Requests
Study Attribution
  • Principal Investigator
    • James N. Ingle, MD. Mayo Clinic, Rochester, MN, USA
  • Institute
    • National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD, USA
  • Funding Source
    • GM 61388. National Institutes of Health, Bethesda, MD, USA