Effect of prevention strategies on survival and quality-adjusted survival of women with BRCA1/2 mutations: an updated decision analysis.
OBJECTIVE
This study updates findings regarding the effects of prophylactic surgery, chemoprevention, and surveillance on the survival and quality-adjusted survival of women who test positive for BRCA1/2 mutations.


METHODS
Markov modeling of outcomes was performed in a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations. The model incorporated breast and ovarian cancer incidence rates from the literature and mortality rates from the Surveillance, Epidemiology, and End Results Program. Quality adjustment of survival estimates were obtained from a survey of women aged 33 to 50 years. Sensitivity analyses were performed of varied assumptions regarding timing and effects of preventive measures on cancer incidence and adverse effects.


RESULTS
A 30-year-old woman could prolong her survival beyond that associated with surveillance alone by use of preventive measures: 1.8 years with tamoxifen, 2.6 years with prophylactic oophorectomy, 4.6 years with both tamoxifen and prophylactic oophorectomy, 3.5 years with prophylactic mastectomy, and 4.9 years with both surgeries. She could prolong her quality-adjusted survival by 2.8 years with tamoxifen, 4.4 years with prophylactic oophorectomy, 6.3 years with tamoxifen and oophorectomy, and 2.6 years with mastectomy, or with both surgeries. The benefits of all of these strategies would decrease if they were initiated at later ages.


CONCLUSIONS
Women who test positive for BRCA1/2 mutations may derive greater survival and quality adjusted survival benefits than previously reported from chemoprevention, prophylactic surgery, or a combination. Observational studies and clinical trials are needed to verify the results of this analysis of the long-term benefits of preventive strategies among BRCA1/2-positive women.
Grann
Victor R
VR
Herbert Irving Comprehensive Cancer Center, Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, New York, NY 10032, USA.
Jacobson
Judith S
JS
Thomason
Dustin
D
Hershman
Dawn
D
Heitjan
Daniel F
DF
Neugut
Alfred I
AI
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000517:prevention & control* / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008390:Markov Chains; D008408:Mastectomy; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000517:prevention & control* / Q000628:therapy; D010052:Ovariectomy; D011336:Probability; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D013629:Tamoxifen