Background: Recent progress in understanding the genetic basis of breast cancer has increased interest in prophylactic mastectomy (PM) as a method of preventing breast cancer.

Objectives: (i) To determine whether prophylactic mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of prophylactic mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes.

Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2002), MEDLINE and Cancerlit (1966 to June 2006), EMBASE (1974 to June 2006), and the WHO International Clinical Trials Registry Platform (WHO ICTRP) search portal (until June 2006). Studies in English were included.

Selection criteria: Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer.

Data collection and analysis: At least two authors independently abstracted data. Data were summarized descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. Data were analyzed separately for bilateral prophylactic mastectomy (BPM) and contralateral prophylactic mastectomy (CPM).

Main results: All 39 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 7,384 women with a wide range of risk factors for breast cancer who underwent PM.BPM studies on the incidence of breast cancer and/or disease-specific mortality reported reductions after BPM particularly for those with BRCA1/2 mutations. For CPM, studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Only one study attempted to control for multiple differences between intervention groups and this study showed no overall survival advantage for CPM at 15 years. Another study showed significantly improved survival following CPM but after adjusting for bilateral prophylactic oophorectomy, the CPM effect on all-cause mortality was no longer significant.Sixteen studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have PM but more variable satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BPM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BPM.Case series reporting on adverse events from PM with or without reconstruction reported rates of unanticipated re-operations from 4% in those without reconstruction to 49% in patients with reconstruction.

Authors' conclusions: Sixteen studies have been published since the last version of the review, without altering our conclusions. While published observational studies demonstrated that BPM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies (ideally randomized trials) are needed. BPM should be considered only among those at very high risk of disease. There is insufficient evidence that CPM improves survival and studies that control for multiple confounding variables are needed.