METHODS: A Markov Monte Carlo simulation model of breast cancer was developed to compare 3 annual breast imaging surveillance strategies versus Clinically based surveillance (no imaging): 1) Mammography only, 2) MRI only, 3) Combined MRI and Mammography. Input parameters were based on information from the published medical literature, existing databases, and expert opinion. Estimates of unobservable parameters were estimated via model calibration to targets obtained from SEER data on breast cancers diagnosed prior to the introduction of mammographic screening (1975-1980).

RESULTS: Results are based on the current best fitting parameter set. For a cohort of 25 year old asymptomatic BRCA1 gene mutation carriers, the model estimates that 67% of women will develop breast cancer during their lifetimes, approximating penetrance estimates. With a strategy of Clinically Based Surveillance, the median diameter of invasive cancers at presentation is 2.6 cm. Life expectancy for the cohort is 72.37 yrs. With the introduction of annual surveillance strategies of Mammography, MRI, or Combined Mammography & MRI, median invasive tumor diameter at diagnosis decreases to 2.0 cm, 1.4 cm, and 1.1 cm, respectively. Despite surveillance, many cancers continue to present clinically as interval cancers (72%, 45%, and 33%, respectively). Cohort life expectancy increases to 72.82 yrs, 73.18 yrs, and 73.82 yrs, respectively. Application of surveillance decreases breast cancer mortality by 7.8%, 9.3%, and 13.5%, respectively. The vast majority of women undergoing surveillance will have at least 1 false-positive screening examination during their lifetime (64%, 86%, and 90% , respectively). Many women also will undergo at least 1 false-positive biopsy (16%, 35%, and 41%, respectively).

CONCLUSIONS: A natural history model of breast cancer in women with BRCA1 mutations has been developed and generates output consistent with available clinical data and published reports. A Combined Mammography & MRI surveillance strategy is most clinically effective, providing BRCA1 mutation carriers with the highest life expectancy, and is the only strategy in which the majority of cancers are detected by surveillance. However, an important trade-off of the Combined Mammography and MRI surveillance strategy is the high rate false-positive screening test results and breast biopsies.