Online Tool to Guide Decisions forBRCA1/2Mutation Carriers

Abstract

A B S T R A C T PurposeWomen 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. MethodsWe 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. ResultsWe 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. ConclusionCancer 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).

Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis

“…The (non-significant) mortality rate reduction after BRRM found in our study corresponds with an absolute survival benefit of 3% according to the Kaplan-Meier estimates, which is comparable to the 3%-5% decrement in survival described by Kurian et al when MRI-based screening was carried out instead of BRRM [14,16]. Our prospective data adds to the modelling study of Kurian, since they better reflect real practice, with only 38% of the women undergoing RRSO in the surveillance group of our study (versus 100% in Kurian's model), during surveillance BC mostly detected at a favourable stage (DCIS/T1N0, while Kurian incorporated BC characteristics at symptomatic detection in the model), and 59% of the BCs in the surveillance group of our study being triple-negative (data not incorporated in Kurian's model).…”

“…So far, survival after BRRM is only studied in mathematical simulation models describing an improved survival for women who opt for riskreducing surgery [12][13][14][15][16], although Kurian et al [14,16] estimated that screening by means of mammography and MRI plus RRSO results in almost similar survival when compared with BRRM combined with RRSO, suggesting that intensive MRI-based surveillance might be a reasonable alternative to BRRM. Arguments to support the latter are (1) MRI detects BC at an early stage in BRCA1/2 mutation carriers [17][18][19][20], (2) in a prospective MRI-detected series of BRCA1/2-associated patients the 5-year cumulative overall survival was 93% (95% CI 79% to 98%) [21], (3) broad implementation of (neo) adjuvant systemic therapy in recent years results in improved BC survival [22].…”

“…The only available information hereon is derived from risk estimates assessed in mathematical models with simulated cohorts, yielding maximal survival probability for BRCA1/2 mutation carriers undergoing both BRRM and RRSO [12][13][14][15][16], although Kurian et al suggested that surveillance using mammography and MRI in combination with RRSO might offer almost comparable survival [14,16]. In view of surveillance aiming at early BC detection, and the current availability of modern (neo)adjuvant treatment strategies, it can indeed be hypothesized that regular surveillance may lead to similar survival when compared with BRRM.…”

Using decision aids to improve treatment choices for women with breast cancer

“…Most surgical DAs, of various formats, were designed for women with early-stage breast cancer and have been reported to improve knowledge and satisfaction with decision-making and/or to reduce decisional conflict (uncertainty) without increasing anxiety or depression [17][18][19][20][21][22][23]. Although a number of DAs have been developed to assist BRCA mutation carriers (in those with or without cancer) in making surgical decisions, these largely address risk-management issues [24][25][26].…”

A hierarchical networked micro-simulator to study grid-integration of renewables and electric vehicles

“…There are a number of commercial and research tools available for micro-simulation, some of which are domain specific. For example, Pensim2 [7] is a pension modeling and simulation tool used in UK, EUROMOD [8][9] is an econometric simulation tool for 15 European countries, PECAS [10] is for urban planning in the US, SimTraffic [11] is for micro-simulation of traffic patterns, CISNET [12][13] is for health science micro-simulation used by US National Cancer Institute, etc. Many of these micro-simulators use scripting languages such as Python to make it easier to use by non-computer scientists (mostly social and economic scientists are users of these tools).…”