Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk
Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk
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DOI：
10.1016/j.ajhg.2020.09.001
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发表时间：
2020-11-05
影响因子：
9.8
通讯作者：
Schmidt, Marjanka K.
中科院分区：
文献类型：
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作者：
Kramer, Iris;Hooning, Maartje J.;Schmidt, Marjanka K.
先前的研究表明，多基因风险评分（PRSs）可以根据女性患原发性浸润性乳腺癌的风险对其进行分层。本研究旨在评估最近验证的313种生殖系变异（PRS313）的PRS与对侧乳腺癌（CBC）风险之间的关系。我们纳入了56,068名自1990年以来被诊断为首次浸润性乳腺癌的欧洲血统女性，随访来自乳腺癌协会联盟。根据PRS313的分布，采用Cox回归分析量化非同步CBC风险（N = 1,027）。我们评估了PRS313与首次诊断年龄、家族史、形态学、ER状态、PR状态和HER2状态以及（新）辅助治疗的相互作用。在亚洲女性的研究中，随访有限，使用logistic回归对340名CBC女性和12133名单侧乳腺癌女性进行了与PRS313相关的CBC风险评估。较高的PRS313与CBC风险增加相关：欧洲人的每标准差风险比(SD) = 1.25 (95%CI = 1.18-1.33)，亚洲人的每标准差风险比= 1.15 （95%CI = 1.02-1.29）。在PRS313的第10百分位中，欧洲妇女CBC的绝对终生风险为12.4%，在第90百分位中为20.5%。我们没有发现与个体特征、原发肿瘤特征或治疗相混淆或相互作用的证据。仅PRS313的c -指数为0.563 （95%CI = 0.547-0.586）。综上所述，PRS313是与CBC风险相关的独立因素，可纳入CBC风险预测模型，有助于改善分层，优化监测和治疗策略。
Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.