Department of Radiology, University of Washington, Seattle Cancer Care Alliance, Seattle.
Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands.
JAMA Oncol. 2022 Apr 1;8(4):587-596. doi: 10.1001/jamaoncol.2021.6204.
Screening mammography and magnetic resonance imaging (MRI) are recommended for women with ATM, CHEK2, and PALB2 pathogenic variants. However, there are few data to guide screening regimens for these women.
To estimate the benefits and harms of breast cancer screening strategies using mammography and MRI at various start ages for women with ATM, CHEK2, and PALB2 pathogenic variants.
DESIGN, SETTING, AND PARTICIPANTS: This comparative modeling analysis used 2 established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate different screening strategies. Age-specific breast cancer risks were estimated using aggregated data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium for 32 247 cases and 32 544 controls in 12 population-based studies. Data on screening performance for mammography and MRI were estimated from published literature. The models simulated US women with ATM, CHEK2, or PALB2 pathogenic variants born in 1985.
Screening strategies with combinations of annual mammography alone and with MRI starting at age 25, 30, 35, or 40 years until age 74 years.
Estimated lifetime breast cancer mortality reduction, life-years gained, breast cancer deaths averted, total screening examinations, false-positive screenings, and benign biopsies per 1000 women screened. Results are reported as model mean values and ranges.
The mean model-estimated lifetime breast cancer risk was 20.9% (18.1%-23.7%) for women with ATM pathogenic variants, 27.6% (23.4%-31.7%) for women with CHEK2 pathogenic variants, and 39.5% (35.6%-43.3%) for women with PALB2 pathogenic variants. Across pathogenic variants, annual mammography alone from 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% (34.6%-38.2%) to 38.5% (37.8%-39.2%) compared with no screening. Screening with annual MRI starting at 35 years followed by annual mammography and MRI at 40 years was estimated to reduce breast cancer mortality by 54.4% (54.2%-54.7%) to 57.6% (57.2%-58.0%), with 4661 (4635-4688) to 5001 (4979-5023) false-positive screenings and 1280 (1272-1287) to 1368 (1362-1374) benign biopsies per 1000 women. Annual MRI starting at 30 years followed by mammography and MRI at 40 years was estimated to reduce mortality by 55.4% (55.3%-55.4%) to 59.5% (58.5%-60.4%), with 5075 (5057-5093) to 5415 (5393-5437) false-positive screenings and 1439 (1429-1449) to 1528 (1517-1538) benign biopsies per 1000 women. When starting MRI at 30 years, initiating annual mammography starting at 30 vs 40 years did not meaningfully reduce mean mortality rates (0.1% [0.1%-0.2%] to 0.3% [0.2%-0.3%]) but was estimated to add 649 (602-695) to 650 (603-696) false-positive screenings and 58 (41-76) to 59 (41-76) benign biopsies per 1000 women.
This analysis suggests that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may reduce breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit.
对于携带 ATM、CHEK2 和 PALB2 种系致病性变异的女性，推荐进行乳房 X 线筛检和磁共振成像（MRI）检查。然而，目前针对这些女性的筛查方案的数据有限。
通过比较建模分析，估计不同起始年龄下使用乳房 X 线摄影和 MRI 进行乳腺癌筛查策略的获益和危害，这些策略适用于携带 ATM、CHEK2 和 PALB2 种系致病性变异的女性。
设计、设置和参与者：本项基于癌症干预和监测建模网络（CISNET）的两项已建立的乳腺癌微模拟模型的比较建模分析，用于评估不同的筛查策略。使用癌症风险估计与易感性相关（CARRIERS）联盟的 12 项基于人群的研究中 32247 例病例和 32544 例对照的汇总数据，估计了特定年龄的乳腺癌风险。通过发表的文献估计了乳房 X 线摄影和 MRI 的筛查性能数据。该模型模拟了 1985 年出生的携带 ATM、CHEK2 或 PALB2 种系致病性变异的美国女性。
在每年进行乳房 X 线筛检的基础上，结合 MRI 筛查，起始年龄为 25 岁、30 岁、35 岁或 40 岁，直至 74 岁。
每 1000 名筛查女性估计的终生乳腺癌死亡率降低、获得的生命年数、乳腺癌死亡人数减少、总筛查检查次数、假阳性筛查和良性活检数量。结果以模型平均值及其范围表示。
携带 ATM 种系致病性变异的女性终生乳腺癌风险的模型估计平均值为 20.9%（18.1%-23.7%），携带 CHEK2 种系致病性变异的女性为 27.6%（23.4%-31.7%），携带 PALB2 种系致病性变异的女性为 39.5%（35.6%-43.3%）。在所有种系致病性变异中，与不筛查相比，从 40 岁到 74 岁每年进行乳房 X 线筛检单独筛查估计可降低 36.4%（34.6%-38.2%）至 38.5%（37.8%-39.2%）的乳腺癌死亡率。从 35 岁开始每年进行 MRI 筛查，然后从 40 岁开始每年进行乳房 X 线和 MRI 筛查，估计可降低 54.4%（54.2%-54.7%）至 57.6%（57.2%-58.0%）的乳腺癌死亡率，每 1000 名筛查女性会有 4661（4635-4688）次假阳性筛查和 1280（1272-1287）例良性活检。从 30 岁开始每年进行 MRI 筛查，然后从 40 岁开始每年进行乳房 X 线和 MRI 筛查，估计可降低 55.4%（55.3%-55.4%）至 59.5%（58.5%-60.4%）的乳腺癌死亡率，每 1000 名筛查女性会有 5075（5057-5093）次假阳性筛查和 1439（1429-1449）例良性活检。对于起始 MRI 筛查的年龄，从 30 岁开始，而不是从 40 岁开始每年进行乳房 X 线筛查，对降低平均死亡率的影响不大（0.1%[0.1%-0.2%]至 0.3%[0.2%-0.3%]），但估计每 1000 名筛查女性会增加 649（602-695）次假阳性筛查和 58（41-76）例良性活检。
本分析表明，对于携带 ATM、CHEK2 和 PALB2 种系致病性变异的女性，从 30 岁至 35 岁开始每年进行 MRI 筛查，然后从 40 岁开始每年进行 MRI 和乳房 X 线筛查，可能会使乳腺癌死亡率降低 50%以上。在 MRI 筛查的情况下，40 岁之前进行乳房 X 线筛查可能不会带来额外的获益。
