BRCA1和BRCA2致病变异携带者患乳腺癌后的第二原发性癌症风险。
Second Primary Cancer Risks After Breast Cancer in and Pathogenic Variant Carriers.
作者信息
Allen Isaac, Hassan Hend, Walburga Yvonne, Huntley Catherine, Loong Lucy, Rahman Tameera, Allen Sophie, Garrett Alice, Torr Bethany, Bacon Andrew, Knott Craig, Jose Sophie, Vernon Sally, Lüchtenborg Margreet, Pethick Joanna, Santaniello Francesco, Goel Shilpi, Wang Ying-Wen, Lavelle Katrina, McRonald Fiona, Eccles Diana, Morris Eva, Hardy Steven, Turnbull Clare, Tischkowitz Marc, Pharoah Paul, Antoniou Antonis C
机构信息
Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom.
National Disease Registration Service, National Health Service England, London, United Kingdom.
出版信息
J Clin Oncol. 2025 Feb 20;43(6):651-661. doi: 10.1200/JCO.24.01146. Epub 2024 Oct 29.
PURPOSE
Second primary cancer (SPC) risks after breast cancer (BC) in pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.
METHODS
We followed 25,811 females and 480 males diagnosed with BC and tested for germline PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks.
RESULTS
There were 1,840 and 1,750 female PV carriers. Compared with population incidences, carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without PVs on testing, carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% ( carriers), 12%/3.0%/6.2% ( carriers), and 3.6%/0.4%/4.9% (noncarriers). Male carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers.
CONCLUSION
Survivors of BC carrying and PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.
目的
携带致病性变异（PV）的乳腺癌（BC）患者发生第二原发性癌症（SPC）的风险尚不确定。我们通过将基因检测数据与全国性疾病登记服务和医院事件统计电子健康记录进行创新性关联，估算了相对风险和绝对风险。
方法
我们对1995年至2019年间在英国国民医疗服务体系（NHS）临床遗传学中心被诊断为BC并接受种系PV检测的25,811名女性和480名男性进行随访，直至SPC诊断、死亡、迁移、对侧乳房/卵巢手术加1年，或2020年12月31日。我们使用英国人群发病率估算标准化发病比（SIR），使用Cox回归比较携带者与非携带者的风险比（HR），以及Kaplan-Meier 10年累积风险。
结果
有1840名女性PV携带者和1750名男性PV携带者。与人群发病率相比，携带者发生对侧乳腺癌（CBC；SIR，15.6 [95% CI，11.8至20.2]）、卵巢癌（SIR，44.0 [95% CI，31.4至59.9]）、非乳房/卵巢联合癌（SIR，2.18 [95% CI，1.59至2.92]）、结直肠癌（SIR，4.80 [95% CI，2.62至8.05]）和子宫内膜癌（SIR，2.92 [95% CI，1.07至6.35]）的SPC风险升高。携带者发生CBC（SIR，7.70 [95% CI，5.45至10.6]）、卵巢癌（SIR，16.8 [95% CI, 10.3至26.0]）、胰腺癌（SIR，5.42 [95% CI，2.09至12.5]）和非乳房/卵巢联合癌（SIR，1.68 [95% CI，1.24至2.23]）的SPC风险升高。与检测时无PV的女性相比，携带者发生CBC（HR，3.60 [95% CI，2.65至4.90]）、卵巢癌（HR，33.0 [95% CI，19.1至57.1]）、非乳房/卵巢联合癌（HR，1.45 [95% CI，1.05至2.01]）和结直肠癌（HR，2.93 [95% CI，1.53至5.62]）的SPC风险升高。携带者发生CBC（HR，2.40 [95% CI，1.70至3.40]）、卵巢癌（HR，12.0 [95% CI，6.70至21.5]）和胰腺癌（HR，3.56 [95% CI，1.34至9.48]）的SPC风险升高。10年累积CBC、卵巢癌和非乳房/卵巢联合癌风险分别为16%/6.3%/7.8%（携带者）、12%/3.0%/6.2%（携带者）和3.6%/0.4%/4.9%（非携带者）。男性携带者发生CBC（HR，13.1 [95% CI，1.19至146]）和前列腺癌（HR，5.61 [95% CI，1.96至16.0]）的SPC风险高于非携带者。
结论
携带和PV的BC幸存者发生SPC的风险较高。他们可能受益于强化监测和降低风险措施。
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