Abstract

<div>Abstract<p><b>Background:</b> Women with inherited mutations in the <i>BRCA1</i> or <i>BRCA2</i> (<i>BRCA1</i>/<i>2</i>) genes are recommended to undergo a number of intensive cancer risk-reducing strategies, including prophylactic mastectomy, prophylactic oophorectomy, and screening. We estimate the impact of different risk-reducing options at various ages on life expectancy.</p><p><b>Methods:</b> We apply our previously developed Monte Carlo simulation model of screening and prophylactic surgery in <i>BRCA1</i>/<i>2</i> mutation carriers. Here, we present the mathematical formulation to compute age-specific breast cancer incidence in the absence of prophylactic oophorectomy, which is an input to the simulation model, and provide sensitivity analysis on related model parameters.</p><p><b>Results:</b> The greatest gains in life expectancy result from conducting prophylactic mastectomy and prophylactic oophorectomy immediately after <i>BRCA1</i>/<i>2</i> mutation testing; these gains vary with age at testing, from 6.8 to 10.3 years for <i>BRCA1</i> and 3.4 to 4.4 years for <i>BRCA2</i> mutation carriers. Life expectancy gains from delaying prophylactic surgery by 5 to 10 years range from 1 to 9.9 years for <i>BRCA1</i> and 0.5 to 4.2 years for <i>BRCA2</i> mutation carriers. Adding annual breast screening provides gains of 2.0 to 9.9 years for <i>BRCA1</i> and 1.5 to 4.3 years for <i>BRCA2</i>. Results were most sensitive to variations in our assumptions about the magnitude and duration of breast cancer risk reduction due to prophylactic oophorectomy.</p><p><b>Conclusions:</b> Life expectancy gains depend on the type of <i>BRCA</i> mutation and age at interventions. Sensitivity analysis identifies the degree of breast cancer risk reduction due to prophylactic oophorectomy as a key determinant of life expectancy gain.</p><p><b>Impact:</b> Further study of the impact of prophylactic oophorectomy on breast cancer risk in <i>BRCA1</i>/<i>2</i> mutation carriers is warranted. <i>Cancer Epidemiol Biomarkers Prev; 21(7); 1066–77. ©2012 AACR.</i></p></div>

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