The availability of genetic testing for inherited mutations in the BRCA1 and BRCA2 genes provides potentially valuable information to women at high risk of breast or ovarian cancer. Unfortunately, carriers of these mutations have relatively few clinical management options to reduce their cancer risk. The investigators propose a study in response to the NCI's program announcement """"""""Clinical Epidemiology Studies in Hereditary Breast/Ovarian Cancer"""""""". They propose to evaluate the role of prophylactic surgery in reducing breast and ovarian cancer risk and mortality in BRCA1 and BRCA2 mutation carriers. Specifically, they propose: 1) to estimate the reduction in cancer risk following prophylactic surgery; 2) to estimate the reduction in cancer mortality following prophylactic surgery; 3) to evaluate differences in type of prophylactic mastectomy in breast cancer risk reduction; and 4) evaluate the psychosocial implications of prophylactic mastectomy or prophylactic oophorectomy, including measurement of mental health, satisfaction and quality of life. Two groups of women will be studied. Surgical subjects are those women who have undergone a bilateral prophylactic mastectomy (BPM) or prophylactic oophorectomy (BPO). Women will be followed-up over the course of this project to identify new occurrences of cancer surgery, or other relevant events. This follow-up will also yield longitudinal information about psychosocial adjustment to surgery including distress, depression, quality of life, satisfaction, and vulnerability to subsequent events. The risk of cancer in women who have undergone prophylactic surgery will be compared with cancer risk in controls that have no history of BPM or BPO. All study participants will carry documented disease-causing germline BRCA1/2 mutations. Analyses will be undertaken to specifically evaluate risk and mortality reduction following surgery. As recognized by this program announcement, women who have inherited germline BRCA1/2 mutations and are at extremely high risk of breast and ovarian cancer """"""""must make decisions about managing their cancer risk Ywith only limited scientific information about Ythe efficacy of prophylactic surgery"""""""". The announcement further recognizes that """"""""While prospective studies will eventually provide definitive answers to these question, there is an immediate need to address these issues through retrospective studies based on existing resources such as tissue banks and high-risk clinic registries and research projects"""""""". This proposal will address that immediate and important clinical need.
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