Should women at increased risk for breast and ovarian cancer be randomizedto prophylactic surgery? An ethical and empirical assessment

More information is needed about the relative effectiveness of prophylactic surgery, chemoprevention, and surveillance in reducing breast and ovarian cancer risk in women with an inherited susceptibility mutation. We assessed practical and ethical barriers to conducting randomized clinical trials (R CTs) to compare preventive interventions for breast and ovarian cancer. Eig hty-seven at-risk women who attended an education and counseling session ab out BRCA1/2 testing were asked about their willingness to participate in hy pothetical research studies for breast and ovarian cancer risk reduction. I n addition, 247 Maryland physicians from five specialties completed a mail survey including a question about their likelihood of recommending RCT part icipation to an at-risk woman. Nineteen percent of at-risk women reported w illingness to participate in a hypothetical RCT for breast cancer risk redu ction and 17% for ovarian cancer risk reduction. Women with children and wo men likely to have a prophylactic mastectomy if found to have a susceptibil ity mutation were significantly more willing to participate in an RCT. A ma jority of women would be willing to participate in nonrandomized trials or registries. Fifty-two percent of physicians responded that they would be li kely to recommend RCT participation to a woman carrying a breast cancer sus ceptibility mutation. Oncologists were the most likely to recommend an RCT. Although the results of nonrandomized trials may be difficult to interpret because of such issues as selection bias. Greater feasibility combined wit h fewer ethical concerns make nonrandomized trials a more viable alternativ e to randomized trials for evaluation of preventive interventions for breas t and ovarian cancer when prophylactic surgery is one of the treatments bei ng evaluated.