BRCA1 相关性乳腺癌与 BRCA2 相关性和家族性病例表现不同：荷兰 MRISC 筛查研究的长期随访。

BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study.

机构信息

Erasmus MC, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA, Rotterdam, the Netherlands.

出版信息

J Clin Oncol. 2010 Dec 20;28(36):5265-73. doi: 10.1200/JCO.2009.27.2294. Epub 2010 Nov 15.

DOI:10.1200/JCO.2009.27.2294

PMID:21079137

Abstract

PURPOSE

The Dutch MRI Screening Study on early detection of hereditary breast cancer started in 1999. We evaluated the long-term results including separate analyses of BRCA1 and BRCA2 mutation carriers and first results on survival.

PATIENTS AND METHODS

Women with higher than 15% cumulative lifetime risk (CLTR) of breast cancer were screened with biannual clinical breast examination and annual mammography and magnetic resonance imaging (MRI). Participants were divided into subgroups: carriers of a gene mutation (50% to 85% CLTR) and two familial groups with high (30% to 50% CLTR) or moderate risk (15% to 30% CLTR).

RESULTS

Our update contains 2,157 eligible women including 599 mutation carriers (median follow-up of 4.9 years from entry) with 97 primary breast cancers detected (median follow-up of 5.0 years from diagnosis). MRI sensitivity was superior to that of mammography for invasive cancer (77.4% v 35.5%; P<.00005), but not for ductal carcinoma in situ. Results in the BRCA1 group were worse compared to the BRCA2, the high-, and the moderate-risk groups, respectively, for mammography sensitivity (25.0% v 61.5%, 45.5%, 46.7%), tumor size at diagnosis≤1 cm (21.4% v 61.5%, 40.9%, 63.6%), proportion of DCIS (6.5% v 18.8%, 14.8%, 31.3%) and interval cancers (32.3% v 6.3%, 3.7%, 6.3%), and age at diagnosis younger than 30 years (9.7% v 0%). Cumulative distant metastasis-free and overall survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast cancer were 83.9% (95% CI, 64.1% to 93.3%) and 92.7% (95% CI, 79.0% to 97.6%), respectively, and 100% in the familial groups (n=43).

CONCLUSION

Screening results were somewhat worse in BRCA1 mutation carriers, but 6-year survival was high in all risk groups.

摘要

目的

荷兰磁共振成像（MRI）筛查研究旨在早期发现遗传性乳腺癌，该研究于 1999 年启动。我们评估了长期结果，包括分别对 BRCA1 和 BRCA2 突变携带者的分析以及生存的初步结果。

方法

累积终生风险（CLTR）高于 15%的女性接受了每两年一次的临床乳房检查、每年一次的乳房 X 线照相术和 MRI 筛查。参与者被分为亚组：基因突变携带者（50%至 85%CLTR）和两个具有高（30%至 50%CLTR）或中度风险（15%至 30%CLTR）的家族组。

结果

我们的更新内容包含 2157 名符合条件的女性，其中 599 名突变携带者（入组后中位随访时间为 4.9 年）发现了 97 例原发性乳腺癌（诊断后中位随访时间为 5.0 年）。MRI 的敏感性优于乳房 X 线照相术，可检测出浸润性癌（77.4%比 35.5%；P<.00005），但不能检测出导管原位癌。BRCA1 组的结果与 BRCA2 组、高风险组和中风险组相比，分别在乳房 X 线照相术的敏感性（25.0%比 61.5%、45.5%、46.7%）、诊断时肿瘤直径≤1cm（21.4%比 61.5%、40.9%、63.6%）、导管原位癌比例（6.5%比 18.8%、14.8%、31.3%）和间期癌（32.3%比 6.3%、3.7%、6.3%）以及诊断时年龄小于 30 岁（9.7%比 0%）方面的结果较差。42 例 BRCA1/2 突变携带者的浸润性乳腺癌的 6 年无远处转移生存和总生存分别为 83.9%（95%CI，64.1%至 93.3%）和 92.7%（95%CI，79.0%至 97.6%），家族组（n=43）的结果均为 100%。