Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation
Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation
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DOI：
10.1038/sj.bjc.6604830
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发表时间：
2009-01-22
影响因子：
8.8
通讯作者：
Narod, S. A.
中科院分区：
文献类型：
--
作者：
Metcalfe, K. A.;Finch, A.;Narod, S. A.
在加拿大，对于有显著乳腺癌家族史的妇女，可以进行BRCA 1和BRCA 2突变的基因检测。对于大多数接受检测的妇女来说，没有发现BRCA 1或BRCA 2突变，关于乳腺癌风险的咨询是基于对谱系的审查。在这项前瞻性研究中，我们评估了有乳腺癌家族史的女性患乳腺癌的风险，并且先证者的BRCA 1或BRCA 2突变检测结果为阴性。确定了50岁以下患有两种或两种以上乳腺癌的家庭，或者在任何年龄患有三种乳腺癌的家庭，以及BRCA 1或BRCA 2突变检测阴性的家庭。收集了乳腺癌病例的所有一级亲属的癌症状态的随访信息。乳腺癌的标准化发病率（SIR）是根据省级癌症登记处的发病率，通过将观察到的乳腺癌数量除以预期的乳腺癌数量来计算的。共有来自365个家庭的1492名妇女被纳入分析。1492例乳腺癌病例的一级亲属提供了9109人年的随访。65名妇女患乳腺癌，而预期人数为15.2人（SIR = 4.3）。40岁以下妇女的SIR最高（SIR = 14.9），并随着年龄的增长而下降。然而，50至70岁的妇女（每年1%）的绝对风险高于30至50岁的妇女（每年0.4%）。患卵巢癌、结肠癌或任何其他癌症的风险都没有增加。有显著乳腺癌家族史的女性（即50岁以下的两种或更多种乳腺癌，或任何年龄的三种或更多种乳腺癌），但BRCA突变检测阴性的女性患乳腺癌的风险约为四倍。这些家庭中的妇女可能是他莫昔芬化学预防和/或加强乳腺MRI筛查的候选人。
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.