Breast cancer screening in BRCA1 mutation carriers: effectiveness of MR imaging--Markov Monte Carlo decision analysis.
OBJECTIVE
To project intermediate and long-term clinical outcomes of magnetic resonance (MR) imaging screening for breast cancer in women with BRCA1 gene mutations.


METHODS
A microsimulation model was developed to compare three annual screening strategies versus clinical surveillance: (a) mammography, (b) MR imaging, and (c) combined MR imaging and mammography. Input parameters were obtained from the published medical literature, existing databases, and expert opinion. The model was calibrated to targets from the Surveillance Epidemiology and End Results database (1975-1980) compiled during a period prior to the onset of widespread mammographic screening. Sensitivity analysis was performed to evaluate the effect of uncertainty in parameter estimates.


RESULTS
With clinical surveillance, the estimated median diameter of invasive breast cancers at presentation was 2.6 cm. Average life expectancy was 71.15 years. With annual screening with mammography, MR imaging, or combined mammography and MR imaging, median invasive tumor diameters at diagnosis decreased to 1.9, 1.3, and 1.1 cm, respectively. Annual screening with mammography, MR imaging, or combined mammography and MR imaging increased average life expectancy by 0.80 year, 1.10 years, and 1.38 years, respectively, and decreased relative mortality from breast cancer (16.8%, 17.2%, and 22.0%, respectively). Program sensitivity was greater than 50% only with MR imaging screening strategies. The majority of women undergoing screening had one or more false-positive screening examinations (53.8%, 80.2%, and 84.0% for mammography, MR imaging, and combined mammography and MR imaging, respectively). Many women also underwent one or more biopsies for benign disease (11.3%, 26.3%, and 30.3%, respectively). Results were sensitive to BRCA1 penetrance estimates and to MR imaging sensitivity in the detection of ductal carcinoma in situ.


CONCLUSIONS
Annual screening with combined mammography and MR imaging provides BRCA1 mutation carriers with the greatest life expectancy gain and breast cancer mortality reduction. However, an important trade-off of this strategy is an increased rate of false-positive screening results and biopsies performed for benign disease.
Lee
Janie M
JM
Department of Radiology, Institute for Technology Assessment, Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, 101 Merrimac St, 10th Floor, Boston, MA 02114, USA. jlee45@partners.org
Kopans
Daniel B
DB
McMahon
Pamela M
PM
Halpern
Elkan F
EF
Ryan
Paula D
PD
Weinstein
Milton C
MC
Gazelle
G Scott
GS
D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008017:Life Expectancy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008327:Mammography; D008390:Markov Chains; D008403:Mass Screening / Q000379:methods*; D009010:Monte Carlo Method; D018426:SEER Program; D014481:United States / Q000453:epidemiology