关于家族性乳腺癌风险的研究，通常忽略了家族史的动态变化。对于有乳腺癌家族史的女性，尤其对于年轻女性，如果考虑其亲属的癌症发生时间，那么可以对其乳腺癌风险进行更精准的推算。
2020年3月10日，美国癌症学会《癌症》在线发表德国癌症研究中心、海德堡大学、乌干达马凯雷雷大学、瑞典隆德大学、美国纽约西奈山伊坎医学院、日本岛根大学的研究报告，探讨了将癌症诊断时间点纳入一级和二级亲属乳腺癌家族风险评定的效果。
该队列研究对瑞典全国1931年后出生的509万9172例女性1958～2015年随访数据进行回顾分析，通过3种方法对一级和二级亲属乳腺癌家族风险进行评定：
将家族史作为静态变量（有无乳腺癌亲属）
将家族史作为累积历史（乳腺癌状态：诊断、失访、死亡）
将家族史作为动态变量（乳腺癌诊断时间）
结果，对于年龄<50岁的女性，动态法与静态法或累积法相比，乳腺癌家族风险大多较高，例如一级亲属乳腺癌家族风险：
静态法：2.6%（95%置信区间：2.5%～2.7%）
累积法：2.4%（95%置信区间：2.3%～2.4%）
动态法：3.1%（95%置信区间：3.0%～3.2%）
对于年龄<50岁的女性，其姐妹有、无乳腺癌史相比：
静态法：乳腺癌风险高1.40倍（95%置信区间：1.31～1.48）
累积法：乳腺癌风险高1.66倍（95%置信区间：1.57～1.76）
动态法：乳腺癌风险高2.25倍（95%置信区间：2.07～2.51）
因此，该研究结果表明，动态法比较适合乳腺癌家族风险预测，累积法最实用但不利于乳腺癌家族风险预测，静态法适用于病因影响和风险归因研究。
Cancer. 2020 Mar 10. [Epub ahead of print]
Familial risk of breast cancer by dynamic, accumulative, and static definitions of family history.
Mukama T, Kharazmi E, Sundquist K, Sundquist J, Brenner H, Fallah M.
German Cancer Research Center, Heidelberg, Germany; University of Heidelberg, Heidelberg, Germany; Makerere University, Kampala, Uganda; Lund University, Malmo, Sweden; Icahn School of Medicine at Mount Sinai, New York, New York; Shimane University, Shimane, Japan.
Considering the timing of cancer events in relatives of women with a family history of breast cancer yields more accurate risk estimates, particularly among young women. In the current study, the authors assessed the effect of incorporating the timing of cancer diagnosis events into the assessment of familial risks of breast cancer in first-degree and second-degree relatives in a nationwide cohort study.
BACKGROUND: Familial breast cancer risk studies usually overlook the dynamic nature of family history.
METHODS: The authors assessed the effect of incorporating the timing of cancer diagnosis events into the assessment of familial risks of breast cancer in first-degree and second-degree relatives in a nationwide cohort study of 5,099,172 women (follow-up was between 1958-2015). Family history was assessed using 3 approaches: 1) as a static variable (ever having a relative with breast cancer); 2) as accumulative history; and 3) as a dynamic variable (time-dependent variable).
RESULTS: For women aged <50 years, familial risk was mostly higher when family history was assessed as a dynamic variable compared with using a static or accumulative family history. For example, the cumulative risk of receiving a breast cancer diagnosis until age 50 years for women with a history of breast cancer in 1 first-degree relative was 2.6% (95% CI, 2.5%-2.7%) using the static method, 2.4% (95% CI, 2.3%-2.4%) using the accumulative method, and 3.1% (95% CI, 3.0%-3.2%) using the dynamic method. Relative risk in women aged <50 years with a breast cancer diagnosis in a sister was 1.40-fold (95% CI, 1.31-fold to 1.48-fold) using the static method, 1.66-fold (95% CI, 1.57-fold to 1.76-fold) using the accumulative method, and 2.28-fold (95% CI, 2.07-fold to 2.51-fold) using the dynamic method.
CONCLUSIONS: The results of the current study demonstrated that assessing family history as static, accumulative, or dynamic results in different familial risk estimates. The answer as to which method to use for family history assessment depends on the implications of the study, with the dynamic method appearing to be better suited for risk stratification studies, the accumulative method being the most convenient in practice and the least favored for risk prediction, and the static method being suitable for etiological impact and risk attribution studies.
KEYWORDS: breast cancer, familial risk, family history, prospective study, time-dependent
DOI: 10.1002/cncr.32815
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