Metcalfe K A, Finch A, Poll A, Horsman D, Kim-Sing C, Scott J, Royer R, Sun P, Narod S A
Lawrence S Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada.
Br J Cancer. 2009 Jan 27;100(2):421-5. doi: 10.1038/sj.bjc.6604830. Epub 2008 Dec 16.
Genetic testing for mutations in BRCA1 and BRCA2 is available in Canada for women with a significant family history of breast cancer. For the majority of tested women, a BRCA1 or BRCA2 mutation is not found, and counselling regarding breast cancer risk is based on the review of the pedigree. In this prospective study, we estimate breast cancer risks in women with a family history of breast cancer and for whom the proband tested negative for a mutation in BRCA1 or BRCA2. Families with two or more breast cancers under the age of 50 years, or with three cases of breast cancer at any age, and who tested negative for a BRCA1 or BRCA2 mutation were identified. Follow-up information on cancer status was collected on all first-degree relatives of breast cancer cases. The standardised incidence ratios (SIRs) for breast cancer were calculated by dividing the observed numbers of breast cancer by the expected numbers of breast cancers, based on the rates in the provincial cancer registries. A total of 1492 women from 365 families were included in the analyses. The 1492 first-degree relatives of breast cancer cases contributed 9109 person-years of follow-up. Sixty-five women developed breast cancer, compared to 15.2 expected number (SIR=4.3). The SIR was highest for women under the age of 40 (SIR=14.9) years and decreased with increasing age. However, the absolute risk was higher for women between the age of 50 and 70 (1% per year) years than for women between 30 and 50 (0.4% per year) years of age. There was no elevated risk for ovarian, colon or any other form of cancer. Women with a significant family history of breast cancer (ie, two or more breast cancers under the age of 50 years, or three or more breast cancers at any age), but who test negative for BRCA mutations have approximately a four-fold risk of breast cancer. Women in these families may be candidates for tamoxifen chemoprevention and/or intensified breast screening with an MRI.
在加拿大，有乳腺癌家族病史的女性可进行BRCA1和BRCA2基因突变检测。对于大多数接受检测的女性而言，未发现BRCA1或BRCA2基因突变，关于乳腺癌风险的咨询是基于家系回顾。在这项前瞻性研究中，我们评估了有乳腺癌家族病史且先证者BRCA1或BRCA2基因突变检测呈阴性的女性患乳腺癌的风险。确定了有两例或更多例50岁以下乳腺癌患者，或有三例任何年龄乳腺癌患者且BRCA1或BRCA2基因突变检测呈阴性的家庭。收集了所有乳腺癌病例一级亲属的癌症状态随访信息。乳腺癌的标准化发病比（SIR）通过将观察到的乳腺癌病例数除以基于省级癌症登记处发病率的预期乳腺癌病例数来计算。分析共纳入了来自365个家庭的1492名女性。1492名乳腺癌病例的一级亲属提供了9109人年的随访。65名女性患乳腺癌，而预期人数为15.2人（SIR = 4.3）。40岁以下女性的SIR最高（SIR = 14.9），且随年龄增长而降低。然而，50至70岁女性（每年1%）的绝对风险高于30至50岁女性（每年0.4%）。卵巢癌、结肠癌或任何其他癌症的风险均未升高。有显著乳腺癌家族病史（即两例或更多例50岁以下乳腺癌患者，或三例或更多例任何年龄乳腺癌患者）但BRCA基因突变检测呈阴性的女性患乳腺癌的风险约为四倍。这些家庭中的女性可能是他莫昔芬化学预防和/或强化MRI乳腺筛查的候选对象。
