Removal of the Ovaries/Fallopian Tubes and CA-125 Screening to Reduce the Risk of Ovarian Cancer in Women at Increased Genetic Risk

This study will evaluate women who are at increased genetic risk of developing ovarian cancer because they or a close relative have a mutation in the BRCA1 or BRCA2 gene (the genes that cause most of the genetic forms of ovarian cancer) or because they have a very strong family history of breast and/or ovarian cancer. The study has two aspects. There will be two groups of subjects in this study. One group of women who will have their ovaries and fallopian tubes surgically removed as a prophylactic (preventive) measure against developing ovarian/fallopian tube cancer. These women will be studied to determine whether the surgery does, in fact, decrease the risk of ovarian or tubal cancer and whether it decreases the risk of breast and other cancers. The tissue removed at surgery will also be investigated to see whether a new way of examining the ovaries after they are removed provides better information about cancer-related tissue changes. A second group of subjects will be women who choose not to have preventive surgery. These women will be followed closely to see if screening with multiple CA-125 blood testing over time (see below) can detect ovarian or tubal cancers in their early stages. Both groups of women will undergo examination of the process by which women decide upon various options for lowering their ovarian cancer risk and a detailed assessment of how their choice impacts their quality of life. It will look at how those who opt for ovariectomy feel after their surgery and how those who choose screening feel during the time of screening. All participants will undergo the following procedures: * Medical history, physical examination, and blood drawing upon entering the study, including blood samples for future ovarian cancer research. * Screening mammogram, CA-125 blood test, and transvaginal ultrasound upon entering the study, with yearly repeat mammograms for all participants and yearly transvaginal ultrasound exams for women in the screening arm of the study. CA-125 is a protein found in the blood whose levels are elevated in most women with ovarian cancer. Transvaginal ultrasound is a way of taking pictures of the ovaries using sound waves. If the results of these tests are not normal, additional tests may be required to learn the reason for the abnormality. * Questionnaires about personal, medical and family history, ovarian cancer risk factors, medication use, medical choices, and quality of life on entering the study, with repeat quality of life and medication use questionnaires every 6 months during the study period. * Blood samples for follow-up visits and for CA-125 testing every 3 months as a screen for ovarian/fallopian tube cancers. Some blood from these samples will be saved for future ovarian cancer research. * Semi-annual report during the duration of the study regarding health and quality of life changes that occur over the prior 6-month period. Researchers will use the pattern and rate of change of CA-125 levels over time in women in the screening group to decide if more tests are needed to test for ovarian cancer. Women in the surgery portion will undergo surgical removal of their ovaries and fallopian tubes. The removed tissues will be studied using new methods to examine the cells more closely than usual, and a portion of the tissues will be stored for future research on ovarian cancer. This study is being conducted in collaboration with the Gynecologic Oncology Group (GOG), and is designated GOG Protocol 0199. Subjects may join the study at any participating GOG institution (http://www.gog.org).