Survival Analysis of Cancer Risk Reduction Strategies for BRCA1/2 Mutation Carriers

Department of Health Research and Policy, Stanford University, Palo Alto, California, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 12/2009; 28(2):222-31. DOI: 10.1200/JCO.2009.22.7991
Source: PubMed

ABSTRACT Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death.
We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers.
With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%).
Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.

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Available from: Allison W Kurian, Aug 04, 2015
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    • "Our model suffers from the following limitations. Since the one-step transition probabilities were adopted from [11], the definition of state vector in our model for a mutation carrier had to be restricted. For example, we could not consider various stages of ovarian cancer and recurrence of breast cancer, as this would require more granular data, than what is currently available, to generate the necessary one-step transition probabilities. "
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    ABSTRACT: Women with BRCA1/2 mutations have higher risk for breast and ovarian cancers. Available intervention actions include prophylactic surgeries and breast screening, which vary significantly in cost, cancer prevention, and in resulting death from other causes. We present a model designed to yield optimal intervention strategies for mutation carriers with age between 30 and 65 and any prior intervention history. Methods A Markov decision process (MDP) model is developed that considers yearly state transitions for the mutation carriers and state dependent intervention actions. State is defined as a vector comprising mutation type, health states, prior intervention actions, and age. A discounted value iteration algorithm is used to obtain optimal strategies from the MDP model using both cost and quality-adjusted life years (QALYs) as rewards. Results The results from MDP model show that for 30 year old women with BRCA1 mutation and no prior intervention history, the costoptimal strategy is a combination of prophylactic mastectomy (PM) and prophylactic oophorectomy (PO) at age 30 with no screening afterwards. Whereas, the QALYs-optimal strategy suggests PO at age 30 and PM at age 50 with screening afterwards. For BRCA2 mutation carriers of age 30, the cost-optimal strategy is PO at age 30, PM at age 40, and yearly screening only after age 56. Corresponding QALYs-optimal strategy is PM at age 40 with screening. Strategies for all other ages (31 to 65) are obtained and presented. It is also demonstrated that the costoptimal strategies offer near maximum survival rate and near minimum cancer incidence rates by age 70, when compared to other ad hoc strategies.
    04/2014; 19(2). DOI:10.1109/JBHI.2014.2319246
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    ABSTRACT: Women with either BRCA1 or BRCA2 germline mutations have a significantly elevated risk of breast and ovarian cancer. Approximately 60 %–70 % of BRCA1 carriers and 45 %–60 % of BRCA2 carriers will develop a breast cancer by age 70, and there is a lower but very significant risk of developing ovarian cancer in both BRCA1 and BRCA2 carriers. This review summarizes data from both retrospective and prospective studies examining the impact of bilateral prophylactic mastectomy and risk-reducing salpingo-oophorectomy on reducing the risk of developing breast and, for the latter, ovarian cancer. In addition, we review data on the mortality benefit from risk-reducing salpino-oophorectomy.
    Current Breast Cancer Reports 09/2012; 4(3). DOI:10.1007/s12609-012-0086-4
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    ABSTRACT: Genetic alterations are important drivers of breast cancer development. Rare, high penetrance mutations, including BRCA1 and BRCA2, account for a minority of breast cancer cases. Recent advances in genomic sequencing technologies have aided the search for additional genetic modifiers of breast cancer risk. An increasing number of risk-associated single nucleotide polymorphisms (SNPs) are being identified. These SNPs are relatively common in the studied populations, and while they generally confer a small increase in risk individually, they may act in combination to alter risk more substantially. This review synthesizes the current understanding of these genetic polymorphisms and breast cancer risk, and discusses experiences and challenges with implementing them into existing risk models and into clinical practice. As additional SNPs are discovered and risk estimates are refined, the aim will be to use this information to guide personalized decisions around managing risk, and to deepen our understanding of breast carcinogenesis.
    Current Breast Cancer Reports 12/2012; 4(4). DOI:10.1007/s12609-012-0091-7
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