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Was Angelina Jolie Right? Optimizing Cancer Prevention Strategies Among BRCA Mutation Carriers
Decision Analysis ( IF 2.5 ) Pub Date : 2017-09-01 , DOI: 10.1287/deca.2017.0352
Eike Nohdurft 1 , Elisa Long 2 , Stefan Spinler 1
Affiliation  

Female carriers of a BRCA1 or BRCA2 genetic mutation face significantly elevated risks of cancer, with 45%-65% of women developing breast cancer and 15%-39% developing ovarian cancer in their lifetimes. Prophylactic surgery options to reduce cancer risk include a bilateral mastectomy BM, bilateral salpingo-oophorectomy BSO, or both surgeries. No comprehensive model providing recommendations at which age to perform the surgeries to optimize quality-adjusted life years QALYs exists. Using available clinical data, we develop a Markov decision process model of a mutation carrier's health states and corresponding transitions, including age-dependent breast and ovarian cancer risk, distribution of each cancer subtype and stage, and mortality. We convert the problem to a linear program to solve for the optimal surgery sequence that maximizes the carrier's expected lifetime QALYs under varying assumptions about individual patient preferences on postsurgery quality of life, fertility considerations, advances in cancer screening or treatment, and others. Baseline results demonstrate that a QALY-maximizing sequence recommends BM between ages 30 and 60 and BSO after age 40. Surgeries are recommended later for BRCA2 mutation carriers, given their lower risk for both cancers compared to BRCA1 mutation carriers. We derive structural properties from the model and show that when a carrier has already undergone one surgery, there exists an optimal control limit beyond which performing the other surgery is always QALY maximizing.

中文翻译:

安吉丽娜·朱莉(Angelina Jolie)对吗?优化BRCA突变携带者的癌症预防策略

BRCA1或BRCA2基因突变的女性携带者面临着罹患癌症的风险显着升高,一生中有45%-65%的女性患乳腺癌,而15%-39%的患卵巢癌。降低癌症风险的预防性手术选择包括双侧乳房切除术BM,双侧输卵管卵巢切除术BSO或两种手术。没有全面的模型可以提供建议,建议在哪个年龄进行手术以优化质量调整生命年QALYs。利用可用的临床数据,我们开发了突变携带者健康状况和相应转变的马尔可夫决策过程模型,包括年龄依赖性乳腺癌和卵巢癌的风险,每种癌症亚型和阶段的分布以及死亡率。我们将问题转换为线性程序,以解决最佳手术顺序,从而在不同的假设(关于个体患者对术后生活质量,生育能力的考虑,癌症筛查或治疗的进展等)的各种假设下,最大化携带者的预期寿命QALY。基线结果表明,QALY最大化序列建议BM在30至60岁之间,BSO在40岁以后。对于BRCA2突变携带者,与BRCA1突变携带者相比,罹患两种癌症的风险均较低,因此建议稍后进行手术。我们从模型中得出结构特性,并表明当载体已经进行过一次手术时,存在最佳控制极限,超过该极限时,执行另一次手术总是QALY最大化。不同患者对手术后生活质量的偏好,生育能力的考虑,癌症筛查或治疗的进展等各种假设下的预期寿命QALY。基线结果表明,QALY最大化序列建议BM在30到60岁之间,BSO在40岁以后。对于BRCA2突变携带者,与BRCA1突变携带者相比,罹患两种癌症的风险均较低,因此建议稍后进行手术。我们从模型中得出结构特性,并表明当载体已经进行过一次手术时,存在最佳控制极限,超过该极限时,执行另一次手术总是QALY最大化。不同患者对手术后生活质量的偏好,生育能力的考虑,癌症筛查或治疗的进展等各种假设下的预期寿命QALY。基线结果表明,QALY最大化序列建议BM在30到60岁之间,BSO在40岁以后。对于BRCA2突变携带者,与BRCA1突变携带者相比,罹患两种癌症的风险均较低,因此建议稍后进行手术。我们从模型中得出结构特性,并表明当载体已经进行过一次手术时,存在最佳控制极限,超过该极限时,执行另一次手术总是QALY最大化。基线结果表明,QALY最大化序列建议BM在30到60岁之间,BSO在40岁以后。对于BRCA2突变携带者,与BRCA1突变携带者相比,罹患两种癌症的风险均较低,因此建议稍后进行手术。我们从模型中得出结构特性,并表明当载体已经进行过一次手术时,存在最佳控制极限,超过该极限时,执行另一次手术总是QALY最大化。基线结果表明,QALY最大化序列建议BM在30到60岁之间,BSO在40岁以后。对于BRCA2突变携带者,与BRCA1突变携带者相比,罹患两种癌症的风险均较低,因此建议稍后进行手术。我们从模型中得出结构特性,并表明当载体已经进行过一次手术时,存在最佳控制极限,超过该极限时,执行另一次手术总是QALY最大化。
更新日期:2017-09-01
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