Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-Oophorectomy in BRCA1 or BRCA2 Mutation Carriers

Timothy R. Rebbeck; Noah D. Kauff; Susan M. Domchek

Disclosures

J Natl Cancer Inst. 2009;101(2):80-87. 

In This Article

Methods

Search Strategy

To identify all reports of RRSO in BRCA1/2 mutation carriers, we searched the PubMed database using the search terms "oophorectomy" and "BRCA1" or "BRCA2." This search yielded 346 studies that were published between January 1999 and December 2007: 309 that included the term "BRCA1" in the title and 267 that included the term "BRCA2" were identified. We then evaluated the full text of these citations to identify articles presenting primary data that provided estimates of risk reduction due to RRSO. No publications were excluded based on quality, sample size, language of publication, or other objective criteria related to study design and analysis. However, some publications that reported RRSO in BRCA1/2 mutation carriers were not included because they did not estimate risk reduction. These included case reports, psychosocial or behavioral studies, commentaries, and clinical recommendations. Because the number of BRCA1/2 mutation carriers is relatively limited and most research groups studying these women are in routine communication and collaborate with one another, we also undertook personal communications with all of the researchers or consortia that have large series of BRCA1/2 mutation carriers and were known to have data that could have been used to report data on this topic. This search did not reveal any additional unpublished studies.

Statistical Analysis

Data were obtained from published estimates as published in the original articles. We undertook a fixed-effects meta-analysis using the hazard ratios (HRs) and/or odds ratios (as published in the original reports) to estimate the pooled relative risks and 95% confidence intervals (CIs). When two or more studies had overlapping study samples, we included only one published report from each group. Of the studies identified here, sample overlaps were noted in the studies of Rebbeck et al.,[8,9] Domchek et al.,[13] and Kauff et al.[16] and in those of Kauff et al.[10,16] Therefore, only Kauff et al.,[16] which had the largest sample size of these five studies, was chosen for inclusion in the meta-analysis. There were no apparent overlaps among the other datasets, although we cannot rule out the possibility that a few individuals had participated in more than one study.

We carried out separate meta-analyses in BRCA1 mutation carriers, BRCA2 mutation carriers, and among women who carried either BRCA1 or BRCA2 mutations (denoted BRCA1/2). A chi-square test of homogeneity among the individual risk ratio estimates of the identified studies was also performed. To evaluate potential for publication bias, we used the adjusted rank correlation test of Begg and Mazumdar.[20] All analyses were conducted using STATA/SE v9.0 (StatCorp, College Station, TX).

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