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Reference
Complete the bibliographic reference for the article according to AJE format.
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King M-C, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2. JAMA 2001;286:2251-6. |
Category of HuGE information
Specify the types of information (from the list below) available in the article:
- Prevalence of gene variant
- Gene-disease association
- Gene-environment interaction
- Gene-gene interaction
- Genetic test evaluation/monitoring
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3. Gene-environment interaction
5. Genetic test evaluation/monitoring |
Study hypotheses or purpose
The authors study hypotheses or main purpose for conducting the study.
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Purpose: To evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations
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Gene(s)
Identification of the following:
- Gene name
- Chromosome location
- Gene product/function
- Alleles
- OMIM #
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- Gene name: BRCA1
- Chromosome location: 17q21
- Gene product/function: Nuclear cell cycle regulated phosphoproteins of breast epithelium
- Alleles: 185delAG, 300T ® G, 1505insG, 2634delC, 5055delG, 5272(-2)delA
- OMIM#: 113705
- Gene name: BRCA2
- Chromosome location: 13q12.3 (BRCA2 )
- Gene product/function: Nuclear cell cycle regulated phosphoproteins of breast epithelium
- Alleles: 983delACAG, 1529delAAAG, 2041insA, 5215delGTCA, 5273delG, 5445delTTTAAGT, 5950delCT, 6503delTT, 6763ins8, 8765delAG
- OMIM#: 600185
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Environmental factor(s)
Identification of the major environmental factors studied (infectious, chemical, physical, nutritional, and behavioral)
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Tamoxifen treatment |
Health outcome(s)
Identification of the major health outcome(s) studied
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Incident-invasive breast cancer |
Study design
Specification of the type of study design(s)
- Case-control
- Cohort
- Cross-sectional
- Descriptive or case series
- Clinical trial
- Population screening
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2. Cohort
5. Clinical trail |
Cohort definition
For study designs 2, 3, and 6, the following are defined, where available:
- Cohort selection criteria
- Exclusion criteria
- Gender
- Race/ethnicity
- Age
- Time period
- Geographic location
- Number of participants
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- Cohort selection criteria: Eligible for Breast Cancer Prevention Trial (BCPT): $ 35 years with $ 1.66% risk for breast cancer within 5 years after enrollment, estimated by Gail et al. model; have had lobular carcinoma in situ; or be $ 60 years of age. (For study group, previously cancer-free women with inherited BRCA1and BRCA2 mutations who developed breast cancer after entry into BCPT.)
- Exclusion criteria: Protein-terminating mutations in BRCA2 exon 27
- Gender: Women only
- Race/ethnicity: None specified
- Age: See cohort selection criteria above
- Time period: April 1, 1992-September 30, 1999
- Geographic location: Seattle , WA
- Number of participants: 288
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Control definition
For study design 1, the following are defined, if available.
- Control selection criteria
- Matching variables
- Exclusion criteria
- Gender
- Race/ethnicity
- Age
- Time period
- Geographic location
- Number of participants
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N/A |
Assessment of environment factors
For studies that include gene-environment interactions, define the following, if available:
- Environmental factor
- Exposure assessment
- Exposure definition
- Number of participants with exposure data (%
of total eligible)
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- Environmental factor 1: Tamoxifen
- Exposure assessment: Patient report
- Exposure definition: Treatment or no treatment (placebo)
- Participants with exposure data: All
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Genotyping
Specify the following:
- Gene
- DNA source
- Methodology
- Number of participants genotyped (% of total eligible)
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- Gene: BRCA1 and BRCA2
- DNA source: Blood samples
- Methodology: Multiplex PCR designed to amplify the exons and flanking intronic sequences containing splice sites with the use of fluorescence-labeled primers in a single reaction. PCR products were cycle-sequenced and analyzed using an Applied Biosystems model ABI 377 DNA Sequencer. Study sample sequences were compared with consensus genomic. Base pairs were identified with the Phred and Poly-Phred programs.
- Number of participants genotyped: 288 of 320 who developed invasive breast cancer
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Results
Describe the major results under each of the following HuGE categories. Include tables when data are provided:
- Prevalence of gene variant
- Gene-disease association
- Gene-environment interaction
- Gene-gene interaction
- Genetic test evaluation/monitoring
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3. Gene environment interaction
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Placebo |
Tamoxifen |
RR (95% CI) |
BRCA1 mutation |
3 |
5 |
1.67 (0.32-10.70) |
BRCA2 mutation |
8 |
3 |
0.38 (0.06-1.56) |
Wild type |
182 |
87 |
0.48 (0.37-0.61) |
All participants* |
211 |
109 |
0.52 (0.41-0.65) |
*Includes 288 genotyped cases and 32 cases without DNA available.
5. Genetic test evaluation
This study addressed a clinical utility issue: Is the effectiveness of tamoxifen for preventing breast cancer different for women with BRCA1 or BRCA2 mutations? The results show that effectiveness is reduced in women with BRCA1 mutations. |
Conclusion
State the author's overall conclusions from the study |
Tamoxifen reduced breast cancer incidence among healthy BRCA2 carriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the BCPT. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast cancer incidence among healthy women with inherited BRCA1 mutations. Whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women with BRCA1 mutations remains unknown.
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Comments
Provide additional insight, including methodologic issues and/or concerns about the study
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- The study is a controlled clinical trial with gene-environment interaction
- The report did not indicate denominator information or person-year data.
- Only women who developed breast cancer were genotyped; thus, a proper incidence-based analysis (case only) cannot be conducted
- Results based on BRCA1 or BRCA2 status were statistically insignificant.
The major findings were based on small numbers, especially in regards to ER status.
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