The BRCA Cancer Gene as a Useful Predictor for Double Primary Breast and Ovarian Cancer: a Meta-Analysis

Abstract

Objective: Breast cancer is the most common malignancy among women all over the world. Breast cancer genes (BRCA1,2) are associated with hereditary breast and ovarian cancer. As a preventive measure, prophylactic mastectomy and oophorectomy remain controversial. The aim of this systematic review and meta-analysis was to evaluate the existing literature about double primary breast and ovarian cancer among patients and assess their level of risk associated with having a BRCA mutation. Methods:We conducted a MEDLINE, PubMed, EMBASE, SCOPUS, and Google Scholar search up to October, 2013. The level of risk was determined using odds ratios (OR) and 95% confidence intervals (95% CI). Heterogeneity was assessed using the I2. We used a random-effects model for the statistical analysis and pooling of the data. Results: Overall, there were 9 studies with 812 double primary cancer cases and 1292 breast or ovarian cancer controls. The mean age of onset of the first primary cancer is 50 years and 57 years for the second primary cancer (interval 7 years). Among the double primary cancer patients, 57% had a BRCA mutation (95% CI: 0.41-0.72; I2 = 92.41, p < 0.001), 43% a BRCA1 mutation (95% CI: 0.32-0.56; I2 = 87.52, p < 0.001), and 14% a BRCA2 mutation (95% CI: 0.10-0.20; I2 = 44.07, p = 0.07). In the study group with a BRCA mutation positive and a first degree relative history of breast or ovarian cancer the risk of double primary cancer was 5.93 times higher compared with the control group which had no family history (OR:5.93(1.90-18.55), I2 = 80.32, p = 0.006). In the study group with no BRCA mutation but with family history the risk of double primary cancer was 2.96 times higher compared with the control group (OR:2.96 (0.68-12.97), I2 = 76.72, p = 0.01). Thus, when compared with having family history alone, having both a family history and a BRCA mutation increases the risk of double primary cancer from 2.96 to 5.93 times. Conclusion: The BRCA gene is a potentially useful screening tool for the prediction of double primary breast and ovarian cancer. However, the risk associated with having these mutations is not absolute and must be weighed up with other risk factors including family history. Additional screening tools should be further studied to determine their usefulness in clinical surgical practice.