儿童胸部放疗后成年乳腺癌风险预测
对于儿童时期曾经接受胸部放疗的女性，成年后发生乳腺癌的风险极高。针对此类人群，目前缺乏个体化乳腺癌风险预测模型。
2021年5月28日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表纽约纪念医院斯隆凯特林癌症中心、德克萨斯大学MD安德森癌症中心、芝加哥大学医学中心科默儿童医院、明尼苏达大学共济会癌症中心、全国儿童医院、弗雷德哈钦森癌症研究中心、圣裘德儿童研究医院、杜克大学医学中心、荷兰马克西玛公主儿童肿瘤中心、荷兰癌症研究所、鹿特丹大学、德国勃兰登堡医学院、以色列特拉维夫索拉斯基医疗中心的北美儿童癌症存活者研究、荷兰霍奇金后期影响和荷兰儿童癌症长期影响（LATER）队列研究报告，建立并验证了胸部放疗儿童癌症存活者乳腺癌风险预测模型，其中包括治疗相关因素、家族史和生殖因素。
模型建立队列来自北美儿童癌症存活者研究1970～1986年确诊癌症并进行胸部放疗后至少存活5年的1120例年龄≤21岁参与者，随访至20～64岁（中位42岁），其中发生乳腺癌242例。
模型验证队列来自北美儿童癌症存活者研究、荷兰霍奇金后期影响、荷兰儿童癌症长期影响三个队列胸部放疗后至少存活5年的另外1027例年龄≤21岁参与者，随访至20～66岁（中位32岁），其中发生乳腺癌105例。
结果，该模型包括目前年龄、胸部放疗范围、胸部放疗是否初次月经1年内、蒽环类用药史、绝经年龄、一级亲属乳腺癌史。
10年乳腺癌风险预估范围：
30岁女性：2%～23%（曲线下面积：0.63，95%置信区间：0.50～0.73）
40岁女性：5%～34%（曲线下面积，0.67，95%置信区间：0.54～0.84）
风险最高的因素包括40岁以上绝经前女性、初次月经1年内进行斗篷野放疗、一级亲属有乳腺癌史。
该模型的校准度良好，预计与实际所见乳腺癌数量之比为0.92（95%置信区间：0.74～1.16）。
因此，该模型结果表明，胸部放疗儿童癌症存活者的乳腺癌风险各不相同。精准的风险预测，可能有助于完善该人群的监测、咨询、预防策略和研究设计。
相关链接
J Clin Oncol. 2021 May 28. Online ahead of print.
Development and Validation of a Breast Cancer Risk Prediction Model for Childhood Cancer Survivors Treated With Chest Radiation: A Report From the Childhood Cancer Survivor Study and the Dutch Hodgkin Late Effects and LATER Cohorts.
Moskowitz CS, Ronckers CM, Chou JF, Smith SA, Friedman DN, Barnea D, Kok JL, de Vries S, Wolden SL, Henderson TO, van der Pal HJH, Kremer LCM, Neglia JP, Turcotte LM, Howell RM, Arnold MA, Schaapveld M, Aleman B, Janus C, Versluys B, Leisenring W, Sklar CA, Begg CB, Pike MC, Armstrong GT, Robison LL, van Leeuwen FE, Oeffinger KC.
Memorial Sloan Kettering Cancer Center, New York, NY; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Brandenburg Medical School Theodor Fontane, Neuruppin, Germany; The University of Texas MD Anderson Cancer Center, Houston, TX; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Netherlands Cancer Institute, Amsterdam, the Netherlands; University of Chicago Medicine Comer Children's Hospital, Chicago, IL; University of Minnesota Masonic Cancer Center, Minneapolis, MN; Nationwide Children's Hospital, Columbus, OH; Erasmus University, Rotterdam, the Netherlands; Fred Hutchinson Cancer Research Center, Seattle, WA; St Jude Children's Research Hospital, Memphis, TN; Duke University Medical Center, Durham, NC.
PURPOSE: Women treated with chest radiation for childhood cancer have one of the highest risks of breast cancer. Models producing personalized breast cancer risk estimates applicable to this population do not exist. We sought to develop and validate a breast cancer risk prediction model for childhood cancer survivors treated with chest radiation incorporating treatment-related factors, family history, and reproductive factors.
METHODS: Analyses were based on multinational cohorts of female 5-year survivors of cancer diagnosed younger than age 21 years and treated with chest radiation. Model derivation was based on 1,120 participants in the Childhood Cancer Survivor Study diagnosed between 1970 and 1986, with median attained age 42 years (range 20-64) and 242 with breast cancer. Model validation included 1,027 participants from three cohorts, with median age 32 years (range 20-66) and 105 with breast cancer.
RESULTS: The model included current age, chest radiation field, whether chest radiation was delivered within 1 year of menarche, anthracycline exposure, age at menopause, and history of a first-degree relative with breast cancer. Ten-year risk estimates ranged from 2% to 23% for 30-year-old women (area under the curve, 0.63; 95% CI, 0.50 to 0.73) and from 5% to 34% for 40-year-old women (area under the curve, 0.67; 95% CI, 0.54 to 0.84). The highest risks were among premenopausal women older than age 40 years treated with mantle field radiation within a year of menarche who had a first-degree relative with breast cancer. It showed good calibration with an expected-to-observed ratio of the number of breast cancers of 0.92 (95% CI, 0.74 to 1.16).
CONCLUSION: Breast cancer risk varies among childhood cancer survivors treated with chest radiation. Accurate risk prediction may aid in refining surveillance, counseling, and preventive strategies in this population.
KEY OBJECTIVE: To develop and validate a breast cancer risk prediction model applicable to women treated with chest radiation for a childhood cancer.
KNOWLEDGE GENERATED: In this analysis of 2,147 female childhood cancer survivors, a breast cancer risk prediction model was developed and validated. The model includes information on treatment for the childhood cancer and traditional breast cancer risk factors and is available as an online risk calculator.
RELEVANCE: The risk calculator provides personalized breast cancer risk estimates and can be used to counsel patients in clinical practice and design intervention studies.
PMID: 34048292
DOI: 10.1200/JCO.20.02244