Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Breast Cancer Res Treat. 2010 Dec;124(3):643-51. doi: 10.1007/s10549-010-0805-3. Epub 2010 Mar 4.
Accurate estimations of lifetime risks of breast and ovarian cancer are crucial for counselling women from BRCA1/2 families. We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the general population in this region. We identified 1188 female mutation carriers and first-degree female relatives in 185 families with a pathogenic BRCA1 or BRCA2 mutation. The occurrence of breast cancer, contralateral breast cancer and ovarian cancer was recorded. The cumulative incidence of breast cancer by age 70 was 71.4% (95% CI 67.2-82.4%) in BRCA1 and 87.5% (82.4-92.6%) in BRCA2 mutation carriers. For ovarian cancer at age 70, it was 58.9% (53.5-64.3%) in BRCA1 and 34.5% (25.0-44.0%) in BRCA2 mutation carriers. For breast cancer we saw a rise of 24.2% in the cumulative incidence in the seventh decade for BRCA2 mutation carriers versus 6.3% for BRCA1. For ovarian cancer the rise in the seventh decade was 17.3% for BRCA1 mutation carriers and 15.1% for BRCA2. The 10-year risk for contralateral breast cancer was 34.2% (29.4-39.0%) in BRCA1 families and 29.2% (22.9-35.5%) in BRCA2. We show that the incidence of breast and ovarian cancer in BRCA2 mutation carriers and of ovarian cancer in BRCA1 mutation carriers is still high after 60 years. This may justify intensive breast screening as well as oophorectomy even after age 60. The risk of contralateral breast cancer rises approximately 3% per year, which may affect preventive choices.
准确估计乳腺癌和卵巢癌的终生风险对于咨询 BRCA1/2 家族的女性至关重要。因此,我们在荷兰北部确定了 BRCA1/2 突变家族的乳腺癌和卵巢癌外显率,并将其与该地区一般人群的癌症发病率进行了比较。我们确定了 185 个具有致病性 BRCA1 或 BRCA2 突变的家族中的 1188 名女性突变携带者和一级女性亲属。记录了乳腺癌、对侧乳腺癌和卵巢癌的发生情况。BRCA1 突变携带者的乳腺癌累积发病率在 70 岁时为 71.4%(95%CI 67.2-82.4%),BRCA2 为 87.5%(82.4-92.6%)。BRCA1 突变携带者的卵巢癌累积发病率为 70 岁时为 58.9%(53.5-64.3%),BRCA2 为 34.5%(25.0-44.0%)。对于乳腺癌,BRCA2 突变携带者在 70 岁时的累积发病率增加了 24.2%,而 BRCA1 为 6.3%。对于卵巢癌,BRCA1 突变携带者在 70 岁时的发病率上升了 17.3%,BRCA2 为 15.1%。BRCA1 家族的对侧乳腺癌 10 年风险为 34.2%(29.4-39.0%),BRCA2 为 29.2%(22.9-35.5%)。我们表明,BRCA2 突变携带者的乳腺癌和卵巢癌以及 BRCA1 突变携带者的卵巢癌发病率在 60 岁后仍然很高。这可能证明即使在 60 岁以后,也需要进行密集的乳房筛查和卵巢切除术。对侧乳腺癌的风险每年上升约 3%,这可能会影响预防性选择。
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