Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention.
Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention.
复制标题
使用乳腺癌风险相关的多态性来识别乳腺癌化学预防的女性。
DOI：
10.1371/journal.pone.0168601
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Kerlikowske K
中科院分区：
文献类型：
--
作者：
Ziv E;Tice JA;Sprague B;Vachon CM;Cummings SR;Kerlikowske K
选择性雌激素受体调节剂（SERM）和芳香化酶抑制剂（AI）可以预防乳腺癌。美国预防服务工作组建议5年乳腺癌风险≥3%的女性考虑乳腺癌的化学预防。超过70种单核苷酸多态性（SNP）与乳腺癌相关。我们试图确定如何最好地整合来自SNP的风险信息与其他风险因素，对女性进行风险分层以进行化学预防。我们使用了乳腺癌监测联盟（BCSC）风险模型估计的35-69岁女性的风险分布。我们模拟了在BCSC模型中添加70个SNP的效果，并研究了这将如何影响多少女性被重新分类为高于和低于化学预防阈值。我们发现，SNP测试人群的大部分益处是通过测试一小部分人群来实现的。例如，如果对5年BCSC风险>2.0%的女性进行检测（约占所有女性的21%），则可以获得检测所有女性（高于或低于3% 5年风险的女性）的约75%的益处。如果对5年风险>1.5%的女性进行检测（约占所有女性的36%），则可以获得约90%的检测益处。SNP检测对女性进行化学预防的重新分类是有效的，但不太可能对5年风险<1.5%的女性进行重新分类。这些结果可用于实施有效的两步测试方法，以确定可能受益于化学预防的高危妇女。
Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention. We used the risk distribution among women ages 35–69 estimated by the Breast Cancer Surveillance Consortium (BCSC) risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention. We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (~21% of all women), ~75% of the benefit of testing all women (shifting women above or below 3% 5-year risk) would be derived. If women with a 5-year risk of >1.5% are tested (~36% of all women), ~90% of the benefit of testing all women would be derived. SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.