Prevention with tamoxifen or other hormones versus prophylactic surgery in BRCA1/2-positive women: a decision analysis.
OBJECTIVE
Recent randomized controlled trials have shown that tamoxifen and raloxifene may prevent invasive breast cancer. This decision analysis study compares the outcomes of chemoprevention with tamoxifen, raloxifene, or oral contraceptives with the outcomes of prophylactic surgery among women with high-risk BRCA1/2 mutations.


METHODS
We used a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations and constructed a Markov model with Monte Carlo simulations, incorporating cumulative breast and ovarian cancer incidence rates from the literature and survival figures from SEER data. We assumed that prophylactic surgery reduces ovarian cancer risk by 45% and breast cancer risk by 90%, that tamoxifen reduces invasive breast cancer risk by 49%, and that raloxifene has similar efficacy and safety in premenopausal and postmenopausal women. We used data obtained from high-risk women by a time trade-off questionnaire to calculate quality-adjusted life-years. We based our cost estimates for hospital and ambulatory care on Health Care Financing Administration payments, the SEER-HCFA database, and the Pharmacy Fundamental Reference.


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 oophorectomy, 3.4 years (2.7-3.7 years) by having bilateral mastectomy, and 4.3 years (3.6-4.6 years) by having both procedures instead of surveillance alone. Chemoprevention with tamoxifen and raloxifene increased survival by 1.6 years (1.0-2.1 years) and 2.2 years (1.3-2.8 years), respectively. Chemoprevention yielded more quality-adjusted life-years than did prophylactic surgery, even when treatment was delayed to age 40 or 50 years. All these procedures were cost-effective or cost-saving compared with surveillance alone.


CONCLUSIONS
Our model suggests that although surgery may yield more substantial survival and cost benefits, quality of life issues may make chemoprevention a more attractive option for young women at high genetic risk.
Grann
V R
VR
Herbert Irving Comprehensive Cancer Center, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Jacobson
J S
JS
Whang
W
W
Hershman
D
D
Heitjan
D F
DF
Antman
K H
KH
Neugut
A I
AI
D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D015331:Cohort Studies; D003276:Contraceptives, Oral / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008390:Markov Chains; D008408:Mastectomy; D008875:Middle Aged; D009010:Monte Carlo Method; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D010052:Ovariectomy; D011788:Quality of Life; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*; D014157:Transcription Factors / Q000235:genetics*
D016588:Anticarcinogenic Agents; D024682:BRCA2 Protein; D003276:Contraceptives, Oral; D009363:Neoplasm Proteins; D014157:Transcription Factors; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride