A Microsimulation Model for Evaluating the Effectiveness of Cancer Risk Management for BRCA Pathogenic Variant Carriers: miBRovaCAre

Abstract

Objectives: To develop a validated model for evaluating the real-world effectiveness of long-term clinical management strategies for women with germline BRCA1 or BRCA2 pathogenic variants.Methods: A microsimulation model was developed that included a BRCA-specific natural history for breast and ovarian cancer, a clinical framework for carrier follow-up, and cancer risk management strategies (breast screening, risk-reducing mastectomy, and bilateral salpingo-oophorectomy). Adherence rates and outcomes for breast screening and risk-reducing surgery were obtained from BRCA carriers seen through a familial cancer service in Melbourne, Australia. The model was assessed for internal and external validity. The model was used to compare women perfectly adhering to screening recommendations versus actual adherence of the clinical cohort.Results: The model accurately predicted cancer incidence, pathology, and mortality. Using actual adherence for breast screening resulted in additional breast cancer deaths (per 1000 women: BRCA1, 2.7; BRCA2, 1.6) compared with perfect screening adherence. This decreased average life expectancy by 0.30 life-years for BRCA1 and 0.07 life-years for BRCA2. When carriers had access to risk-reducing mastectomy, the benefit from improved screening adherence was not significant. Conclusions:The developed model is a good descriptor of BRCA carriers' lifetime trajectory and its modification by use of risk management strategies alone or in combination. Evaluations of breast screening in BRCA carriers may overestimate the benefits of screening programs unless adherence is considered. By incorporating real-world clinical practice and patient behavior, this model can assist in developing clinical services and improving clinical outcomes for carriers.

Population or family history based BRCA gene tests of breast cancer? A systematic review of economic evaluations

“…Although several genes are attributed to breast cancer, the BRCA genes have been recognized as the most important ones. The risk of developing breast cancer in women who carry the BRCA is considered as 65%, compared with 12% in the general population [ 13 , 14 ]. The risk assessment estimating, managing the preventive interventions are the advantages of BRCA tests for women having an FH of breast cancer, and it avoids a second surgery or having a risk-reduction surgery performed parallel to the treatment surgery for women with the affected breasts [ 15 ].…”

Cost-effectiveness of long-term clinical management of BRCA pathogenic variant carriers

“…The study population has been described previously. 10 The study was approved by the Peter MacCallum Cancer Centre institutional review board.…”

“…This evaluation used a previously developed simulation model for BRCA carrier natural history and cancer risk management. 10 It is a validated discrete-time patient-level model in Python that simulates the development of breast and ovarian cancer in BRCA1 and BRCA2 carriers, and the effect of different clinical management strategies on lifetime health outcomes and health-care costs. Input parameters were obtained from the literature, expert opinion, and individual patient data.…”

“…Additional model details including a description of the cohort used for the patient data, and a list of modeling assumptions were described previously. 10…”

“…Probabilities for breast cancer pathology (grade, tumor size, nodal status, metastasis, and hormone receptors) were obtained from individual patient data. 10 Breast cancer mortality was from the Surveillance, Epidemiology, and End Results program and incorporated hormone receptors, grade, and stage at diagnosis. 12 No difference in survival between BRCA-associated and sporadic breast cancer has been shown after accounting for these prognostic factors.…”