Prevention with tamoxifen or other hormones versus prophylactic surgery inBRCA1/2-positive women: A decision analysis

PURPOSE Recent randomized controlled trials have shown that tamoxifen and raloxifen e may prevent invasive breast cancer. This decision analysis study compares the outcomes of chemoprevention with tamoxifen, raloxifene, or oral contra ceptives with the outcomes of prophylactic surgery among women with high-ri sk BRCA1/2 mutations. PATIENTS AND METHODS We used a simulated cohort of 30-year-old women who tested positive for BRC A1/2 mutations and constructed a Markov model with Monte Carlo simulations, incorporating cumulative breast and ovarian cancer incidence rates from th e literature and survival figures from SEER data. We assumed that prophylac tic surgery reduces ovarian cancer risk by 45% and breast cancer risk by 90 %, that tamoxifen reduces invasive breast cancer risk by 49%, and that ralo xifene has similar efficacy and safety in premenopausal and postmenopausal women. We used data obtained from high-risk women by a time trade-off quest ionnaire to calculate quality-adjusted life-years. We based our cost estima tes for hospital and ambulatory care on Health Care Financing Administratio n payments, the SEER-HCFA database, and the Pharmacy Fundamental RESULTS In our model, a 30-year-old BRCA1/2(+) woman could prolong survival by 0.9 years (95% probability interval, 0.4-1.2 years) by having bilateral oophore ctomy, 3.4 years (2.7-3.7 years) by having bilateral mastectomy, and 4.3 ye ars (3.6-4.6 years) by having both procedures instead of surveillance alone . Chemoprevention with tamoxifen and raloxifene increased survival by 1.6 y ears (1.0-2.1 years) and 2.2 years (1.3-2.8 years), respectively. Chemoprev ention yielded more quality-adjusted life-years than did prophylactic surge ry, even when treatment was delayed to age 40 or 50 years. All these proced ures were cost-effective or cost-saving compared with surveillance alone. DISCUSSION Our model suggests that although surgery may yield more substantial surviva l and cost benefits, quality of life issues may make chemoprevention a more attractive option for young women at high genetic risk.