Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers

Abstract

Comparative effectiveness research has become an integral part of health care planning in most developed countries. In a simulated cohort of women, aged 30–65, who tested positive for BRCA1 or BRCA2 mutations, we compared outcomes of mammography with and without MRI, prophylactic oophorectomy with and without mastectomy, mastectomy alone, and chemoprevention. Methods: Using Treeage 9.02 software, we developed Markov models with 25,000 Monte Carlo simulations and conducted probabilistic sensitivity analysis. We based mutation penetrance rates, breast and ovarian cancer incidence, and mortality rates, and costs in terms of 2009 dollars, on published studies and data from the Surveillance, Epidemiology, and End Results (SEER) Program and the Centers for Medicare and Medicaid Services. We used preference ratings obtained from mutation carriers and controls to adjust survival for quality of life (QALYs). Results: For BRCA1 mutation carriers, prophylactic oophorectomy at $1,741 per QALY, was more cost effective than both surgeries and dominated all other interventions. For BRCA2 carriers, prophylactic oophorectomy, at $4,587 per QALY, was more cost effective than both surgeries. Without quality adjustment, both mastectomy and BSO surgeries dominated all other interventions. In all simulations, preventive surgeries or chemoprevention dominated or were more cost effective than screening because screening modalities were costly. Conclusion: Our analysis suggested that among BRCA1/2 mutation carriers, prophylactic surgery would dominate or be cost effective compared to chemoprevention and screening. Annual screening with MRI and mammography was the most effective strategy because it was associated with the longest quality-adjusted survival, but it was also very expensive.

Factors Associated with Altered Long-Term Well-Being After Prophylactic Salpingo-Oophorectomy Among Women at Increased Hereditary Risk for Breast and Ovarian Cancer

“…However, this population appeared to have high endocrine symptom scores and lower sexual functioning. This has also been more or less described in other publications [5,7,8,15,16].…”

Differences in Natural History between Breast Cancers in BRCA1 and BRCA2 Mutation Carriers and Effects of MRI Screening-MRISC, MARIBS, and Canadian Studies Combined

“…Several other modeling studies have also found that the effectiveness of screening using MRI is only slightly lower than the effectiveness of screening Table 3. The effects of various annual screen protocols on the number of screen-detected cancers and interval cancers and node positives, as would be detected in the studies, as well as the predicted mortality reduction and probability of breast cancer death using MRI and mammography (30)(31)(32), and that screening BRCA1/2 mutation carriers using MRI and mammography is cost-effective (20,(30)(31)(32)(33). However, these modeling studies did not make a distinction between BRCA1 and BRCA2.…”

Managing patients at genetic risk of breast cancer

“…29 MRI has also been shown to be cost-effective when added to mammography and physical examination in women at high risk. 5,32 Adding MRI to the breast cancer screening regimen has been under discussion and has been endorsed by the American Cancer Society in formal recommendations set forth in 2007 for patients with known hereditary cancer syndromes, in untested fi rst-degree relatives of identifi ed genetic mutation carriers, or in women who have an estimated lifetime risk of breast cancer of 20% or more, as determined by models largely dependent on family history. 33 But MRI has a downside-it is less specifi c than mammography.…”