乳腺癌多基因风险评分与生存结局
多基因风险评分PRS由313种常见基因变异组成，并且过优化和广泛验证，与首发乳腺癌和对侧乳腺癌的风险密切相关，对乳腺癌筛查和预防的风险分层具有重要作用。不过，乳腺癌筛查和预防的最终目标是降低死亡率，PRS对于乳腺癌患者生存结局的影响尚不明确，这对PRS能否纳入临床实践至关重要。
多多益善的主人公是谁2023年1月23日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表荷兰癌症研究所、列文虎克医院、鹿特丹大学、莱顿大学、比利时布鲁塞尔欧洲癌症研究治疗组织总部、加拿大西奈山医院、丹麦哥本哈根大学、德国汉诺威医学院、埃朗根纽伦堡大学、英国南安普顿大学、剑桥大学、芬兰赫尔辛基大学、瑞典卡罗林学院、美国旧金山加利福尼亚大学海伦迪勒家族综合癌症中心的乳腺癌协会联盟BCAC和MINDACT试验协作组研究报告，首次探讨了PRS对早期乳腺癌临床病理学特征和术后生存结局的影响。
该研究对BCAC数据库最新婚姻法9万8397例欧洲血统和1万2920例亚洲血统以及欧洲MINDACT试验683例乳腺浸润癌女性进行回顾分析。通过逻辑回归分析PRS与临床病理学特征（包括MINDACT试验70基因特征）的关联。通过多因素比例风险回归对临床病理特征和治疗方法
进行校正后，分析PRS（连续变量，每个标准差）与总生存和乳腺癌相关生存的关联。
结果发现，PRS与肿瘤特征显著相关，PRS较高与较低相比：
∙BCAC：肿瘤分级较低、激素受体阳性比例较高、肿瘤较小
∙MINDACT：70基因风险较低
对临床病理特征和治疗方法进行校正后，PRS与生存结局无显著相关性，PRS较高与较低相比：
∙BCAC欧洲女性
∙总生存风险比：0.96（95%置信区间：0.94～0.97，P<0.0001）
∙校正后风险比：1.01（95%置信区间：0.98～1.05，P=0.46）
∙乳腺癌相关生存风险比：0.96（95%置信区间：0.94～0.98，P=0.001）
∙校正后风险比：1.02（95%置信区间：0.98～1.07，P=0.39）
∙BCAC亚洲女性
∙总生存风险比：0.97（95%置信区间：0.91～1.02，P=0.240）
利脑心胶囊∙校正后风险比：0.96（95%置信区间：0.87～1.07，P=0.48）鲢鱼怎么做好吃
∙乳腺癌相关生存风险比：1.05（95%置信区间：0.93～1.19，P=0.400）
∙笃学好古校正后风险比：0.93（95%置信区间：0.75～1.17，P=0.55）
∙MINDACT
∙总生存风险比：0.91（95%置信区间：0.71～1.17，P=0.450）
∙校正后风险比：0.91（95%置信区间：0.69～1.18，P=0.91）
∙乳腺癌相关生存风险比：1.10（95%置信区间：0.77～1.56，P=0.600）
∙校正后风险比：1.01（95%置信区间：0.69～1.49，P=0.95）
因此，该研究结果表明，PRS较高与较低相比，肿瘤特征较好，但是生存结局相似，故对早期乳腺癌确诊时的临床管理意义不大。不过，对于PRS较高的女性，雌激素受体阳性乳腺癌风险较高，故乳腺癌死亡率可能较高，该信息对于有效的分层筛选程序建模至关重要，利用PRS可以针对最有可能获益的女性采取激素预防策略。
J Clin Oncol. 2023 Jan 23. IF: 50.717
Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival.
Lopes Cardozo JMN, Andrulis IL, Bojen SE, Dork T, Eccles DM, Fasching PA, Hooning MJ, Keeman R, Nevanlinna H, Rutgers EJT, Easton DF, Hall P, Pharoah PDP, van 't Veer LJ, Schmidt MK; Breast Cancer Association Consortium and MINDACT Collaborators.
The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Leiden University Medical Center, Leiden, the Netherlands; European Organisation for Rearch
踩气球and Treatment of Cancer Headquarters, Brusls, Belgium; Lunenfeld-Tanenbaum Rearch Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; University of Copenhagen, Copenhagen, Denmark; Hannover Medical School, Hannover, Germany; Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany; University of Southampton, Southampton, United Kingdom; University of Cambridge, Cambridge, United Kingdom; Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Karolinska Institutet, Stockholm, Sweden; Sodersjukhut, Stockholm, Sweden; UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
PURPOSE: A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.
METHODS: Women with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analys. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.
RESULTS: The PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (
95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.
CONCLUSION什么是对冲: An incread PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an incread risk of dia. This information is crucial for modeling effective stratified screening programs.
