Reference
Complete the bibliographic reference for the article according to AJE format.

Meijers-Heijboer H, Van Geel B, van Putten WLJ, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MBE, Bartels CCM, Verhoog LC, van den Ouweland AMW, Niermeijer MF, Brekelmans CTM, Klijn JGM.  Breast cancer after prophylactic mastectomy in women with a BRCA1 or BRCA2 mutation.  N Eng J Med 2001;345:159-64.

Category of HuGE information
Specify the types of information (from the list below) available in the article:

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

5.Genetic test evaluation

Study hypotheses or purpose
The authors study hypotheses or main purpose for conducting the study

Gene(s)
Identification of the following:

1. Gene name
2. Chromosome location
3. Gene product/function
4. Alleles
5. OMIM #

1. Gene name: BRCA1
2. Chromosome location: 17q21
3. Gene product/function: May regulate gene expression and act as a converging vehicle with which cell regulatory proteins can associate.  The efficient repair of double-strand DNA breaks is linked to BRCA1 tumor suppression function. Involved in transcriptional regulation of p21 in response to DNA damage.
4. Alleles: Variants not specified
5. OMIM #: 113705Gene: BRCA2
   

1. Chromosome location:  13q12.3
2. Gene product/function: May participate in a pathway associated with the activation of double-strand break repair and/or homologous recombination.
3. Alleles:  Variants not specified
4. OMIM #: 600185

Environmental factor(s)
Identification of the major environmental factors studied (infectious, chemical, physical, nutritional, and behavioral)

NA

Health outcome(s)
Identification of the major health outcome(s) studied

Breast Cancer

Intervention
Identification of the intervention  studied

1. Case-control
2. Cohort 
3. Cross-sectional
4. Descriptive or case series
5. Clinical trial
6. Population screening

1. Disease case definition
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants

N/A

1. Control selection criteria
2. Matching variables
3. Exclusion criteria
4. Gender
5. Race/ethnicity
6. Age
7. Time period
8. Geographic location
9. Number of participants

N/A

Cohort definition
For study designs 2, 3, and 6, define the following if available:

1. Cohort selection criteria
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants

1. Cohort selection criteria: All women with documented BRCA1 or BRCA2 mutations who were being monitored for breast cancer because of familial clustering of breast cancer, ovarian cancer, or both at the Daniel den Hoed Cancer Center
2. Exclusion criteria: woman in whom breast cancer was detected at the first screening or who had received a  diagnosis of breast cancer
3. Gender: Female
4. Race/ethnicity: Not specified
5. Age: 23-64 years
6. Time period: 1/1/1992-3/1/2001
7. Geographic location: Rotterdam, the Netherlands
8. Number of participants: 139

1. Environmental factor
2. Exposure assessment
3. Exposure definition
4. Number of participants with exposure data (% of total eligible)

Assessment of intervention
For studies that include the following 

1. Intervention
2. Intervention definition
3. Number of participants with exposure data (% of total eligible)

1. Environmental factor : Prophylactic mastectomy
2. Intervention definition: Individuals who selected prophylactic mastectomy
3. Number of individuals from cohort who selected intervention: 76/139

1. Gene
2. DNA source
3. Methodology
4. Number of participants genotyped (% of total eligible) 

1. Gene: BRCA1, BRCA2
2. DNA source: Not specified
3. Methodology: Linkage analysis (up to 1994 for BRCA1, up to 1995 for BRCA2) and direct mutational analysis from tissue not specified from 1994-2000.
4. Participants genotyped:  All individuals in study (100%)

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

5. Genetic test evaluation

Cox proportional-hazards model showed the effect of prophylactic mastectomy significantly (p=0.003) decreased the incidence of breast cancer (hazard ratio, 0; 95% CI, 0 – 0.36). Adjusting for menopausal status, the protective effect of mastectomy remained statistically significant (p=0.01). 

In surveillance group: Ratio of observed cases to expected cases (based upon published estimates for women with BRCA1 mutation¹) = 8/6.7 = 1.2 (95% CI,#0.4-3.7; p=0.80)

Conclusion
State the author's overall conclusions from the study

In women with a BRCA1 or BRCA2 mutation, prophylactic mastectomy reduces the risk of breast cancer at 3 years of follow-up.

As the authors concluded, the cohort was relatively small, and the follow-up time was only 3 years.  In addition, factors not measured in the study may have contributed to the outcome of lower incidence of breast cancer in the group that chose mastectomy. A potential confounding factor is prophylactic oophorectomy, since more women from the mastectomy group underwent oophorectomy compared to the surveillance group.