Online tool to guide decisions for BRCA1/2 mutation carriers.
OBJECTIVE
Women with BRCA1 or BRCA2 (BRCA1/2) mutations must choose between prophylactic surgeries and screening to manage their high risks of breast and ovarian cancer, comparing options in terms of cancer incidence, survival, and quality of life. A clinical decision tool could guide these complex choices.


METHODS
We built a Monte Carlo model for BRCA1/2 mutation carriers, simulating breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years and prophylactic mastectomy (PM) and/or prophylactic oophorectomy (PO) at various ages. Modeled outcomes were cancer incidence, tumor features that shape treatment recommendations, overall survival, and cause-specific mortality. We adapted the model into an online tool to support shared decision making.


RESULTS
We compared strategies on cancer incidence and survival to age 70 years; for example, PO plus PM at age 25 years optimizes both outcomes (incidence, 4% to 11%; survival, 80% to 83%), whereas PO at age 40 years plus MRI screening offers less effective prevention, yet similar survival (incidence, 36% to 57%; survival, 74% to 80%). To characterize patients' treatment and survivorship experiences, we reported the tumor features and treatments associated with risk-reducing interventions; for example, in most BRCA2 mutation carriers (81%), MRI screening diagnoses stage I, hormone receptor-positive breast cancers, which may not require chemotherapy.


CONCLUSIONS
Cancer risk-reducing options for BRCA1/2 mutation carriers vary in their impact on cancer incidence, recommended treatments, quality of life, and survival. To guide decisions informed by multiple health outcomes, we provide an online tool for joint use by patients with their physicians (http://brcatool.stanford.edu).
Stanford University School of Medicine, Stanford, CA, USA.
Allison W
AW
Kurian
Diego F
DF
Munoz
Peter
P
Rust
Elizabeth A
EA
Schackmann
Michael
M
Smith
Lauren
L
Clarke
Meredith A
MA
Mills
Sylvia K
SK
Plevritis
D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D003198:Computer Simulation; D003661:Decision Support Techniques; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008327:Mammography; D008408:Mastectomy; D009010:Monte Carlo Method; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D010052:Ovariectomy; D011788:Quality of Life; D016019:Survival Analysis