A systematic review of the literature was conducted to assess the outcomes of preventive interventions (prophylactic surgery, intensive cancer screening, and chemoprevention) in women who carry mutations in BRCA1/2 genes, in terms of reducing breast and gynaecological cancer incidence and/or mortality. A search for relevant articles published between 1996 and 2005 (inclusive) was run on Medline, Embase and other databases. From the 749 journal articles retrieved from this search strategy, 18 studies were eligible for this review (2 systematic reviews, 10 cohort studies and 6 case-control studies). The critical appraisal of the studies was performed by two independent reviewers with a list of ad hoc selected criteria. The synthesis of results was qualitative. Mastectomy and prophylactic gynaecological surgery (oophorectomy or salpingooophorectomy) reduced breast and gynaecological cancer incidence in carriers of BRCA mutations, by comparison to surveillance. However, all the studies presented flaws in internal and external validity, none of these preventive interventions is riskfree, and protection against breast and gynaecological cancer, as well as other cancers linked to BRCA mutations, is incomplete. No studies comparing surveillance programmes of varying intensity were found. Exposure to drugs (tamoxifen, and oral contraceptives) in women carrying BRCA mutations was assessed through a limited number of papers. All of these were case-control studies with prevalent cases and presented major methodological flaws. ' 2007 Wiley-Liss, Inc.Key words: BRCA 1 or BRCA 2; prophylactic mastectomy; prophylactic oophorectomy; chemoprevention; surveillance Breast cancer is the most commonly diagnosed cancer after nonmelanoma skin cancer in women, and it is the second leading cause of cancer-related deaths. Although less common, ovarian cancer is associated with high morbidity and mortality rates and ranks as the fourth cause of all cancer-related deaths among Western women. 1,2 Most breast cancers (70-80%) occur in women with no family history of cancer (sporadic cancers). However, the remaining cases are all linked to a family history of cancer. The aggregation of breast cancer cases in a given family has also been related to an increased risk for ovarian cancer. Although different genes have been linked to hereditary cancer, most familial cases of breast and gynecological cancers (ovarian cancer, Fallopian tube cancer and carcinoma of the peritoneum) are associated with mutations in the BRCA1 and BRCA2 genes.Germ line mutations in BRCA1/2 genes confer a higher risk of breast and ovarian cancer, clearly above the risk for the general population. However, the average magnitude of these risks is uncertain and may depend on context (intensity of family history, ethnic group, environmental factors, etc.). In women carrying BRCA1 mutations, the average cumulative risk of cancer by age 70 years ranged between 51 and 95% for breast cancer and between 22 and 66% for ovarian cancer. In BRCA 2-mutation carriers, the risks ranged be...

We have systematically reviewed the literature focusing on the performance of surveillance programmes and imaging techniques for the early diagnosis of breast and ovarian cancer in women carrying mutations in BRCA1/2 genes. A search for relevant articles published between 1996 and 2005 (inclusive) was run on Medline, Embase and other databases. Of the 749 articles retrieved, only 13 met the inclusion criteria. Of these, 12 provided information on breast cancer surveillance, 1 on ovarian cancer surveillance and a further study addressed both cancer types. A critical appraisal of the studies was performed using a tool for the quality assessment of diagnostic accuracy studies (QUADAS). The synthesis of results is qualitative. All studies on imaging techniques for the diagnosis of breast cancer indicated that screening MRI had the highest sensitivity (between 77% and 100%). Breast cancer surveillance programmes, including MRI, achieved the highest diagnostic performance (between 83% and 95%) for all women. However, it must be taken into account that biases that may affect the validity of the outcomes were seen in the evaluated studies. Also, MRI is an expensive test with a low positive predictive value and, to date, MRI screening has not been proven to reduce mortality rates in women carrying BRCA1/2 gene mutations. As a result of the scant information and low quality of the papers reviewed, no definitive conclusion could be drawn on the performance of ovarian cancer surveillance in women carrying BRCA1/2 mutations.