Chen Jinbo, Bae Eunchan, Zhang Lingjiao, Hughes Kevin, Parmigiani Giovanni, Braun Danielle, Rebbeck Timothy R
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
JNCI Cancer Spectr. 2020 Apr 23;4(4):pkaa029. doi: 10.1093/jncics/pkaa029. eCollection 2020 Aug.
Use of risk-reducing Salpingo-oophorectomy (RRSO) substantially reduces the risk of ovarian and breast cancer for women who carry a mutation. It is important to adjust for RRSO use in the estimation of penetrance of breast and ovarian cancer.
We searched PubMed for penetrance estimates of breast and ovarian cancer from studies that genotyped individual patients and explicitly adjusted for RRSO use by censoring follow-up at the age of RRSO. We meta-analyzed penetrance estimates from 7 identified studies. We implemented the resulting penetrance estimates in a Mendelian risk prediction model as iplemented in the software package BRCAPRO, which we applied to estimate carrier probabilities in 2 cohorts.
Penetrance estimates by age 70 years for breast cancer were 64.6% (95% confidence interval [CI] = 59.5% to 69.4%) for BRCA1 mutation carriers and 61.0% (95% CI = 48.1% to 72.5%) for BRCA2 mutation carriers, and for ovarian cancer they were 48.3% (95% CI = 38.8% to 57.9%) and 20.0% (95% CI = 13.3% to 29.0%), respectively. When integrated into BRCAPRO, our estimates led to good calibration and different estimates of carrier probabilities for some individuals when evaluating the models in 2 cohorts.
The report updates penetrance estimates for BRCA1/2-associated cancer. We report higher estimates than previously reported, which did not adjust for RRSO. Differential use of RRSO may partially explain heterogeneity in the currently available penetrance estimates. For some individuals, using our estimates in BRCAPRO may result in changes in estimated carrier probabilities, which warrants validation in future studies.
对于携带特定基因突变的女性，实施降低风险的输卵管卵巢切除术（RRSO）可大幅降低患卵巢癌和乳腺癌的风险。在估计乳腺癌和卵巢癌的外显率时，对RRSO的使用情况进行调整很重要。
我们在PubMed上搜索了对个体患者进行基因分型并通过在RRSO年龄时截尾随访明确调整RRSO使用情况的研究中乳腺癌和卵巢癌的外显率估计值。我们对7项已识别研究的外显率估计值进行了荟萃分析。我们将所得的外显率估计值应用于软件包BRCAPRO中实施的孟德尔风险预测模型，该模型用于估计两个队列中的携带者概率。
BRCA1基因突变携带者在70岁时乳腺癌的外显率估计值为64.6%（95%置信区间[CI]=59.5%至69.4%），BRCA2基因突变携带者为61.0%（95%CI=48.1%至72.5%）；卵巢癌的外显率估计值分别为48.3%（95%CI=38.8%至57.9%）和20.0%（95%CI=13.3%至29.0%）。当整合到BRCAPRO中时，我们的估计值在评估两个队列中的模型时产生了良好的校准效果，并且对一些个体的携带者概率估计不同。
本报告更新了BRCA1/2相关癌症的外显率估计值。我们报告的估计值高于先前未对RRSO进行调整时报告的值。RRSO的不同使用情况可能部分解释了当前可用外显率估计值的异质性。对于一些个体，在BRCAPRO中使用我们的估计值可能会导致估计的携带者概率发生变化，这有待未来研究进行验证。
