The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Genetics, Chaim Sheba Medical Center, 52621 Tel-Hashomer, Israel.
Breast Cancer Res Treat. 2012 Apr;132(2):669-73. doi: 10.1007/s10549-011-1886-3. Epub 2011 Nov 24.
BRCA1 and BRCA2 mutation carriers have an increased risk for developing breast (and ovarian) cancer. Non-carriers from within such families (=true negatives) are counseled that their risk for developing breast cancer is similar to that of the average-risk population. Breast cancer diagnosed in a non-carrier from a family with a known mutation is coined phenocopy. The rate of breast cancer phenocopy and the risk for breast cancer in true negatives are unsettled. The rate of phenocopy breast cancer was assessed in non-carriers from Jewish families with a BRCA1 or BRCA2 mutation, identified at the Sheba medical center. Analysis was performed by t test for comparison of mean age at counseling or breast cancer diagnosis, and by calculating a standardized incidence ratio (SIR). Overall, 1318 females from 884 mutation carrying families (620 with BRCA1 264 with BRCA2 mutations) were genotyped, of whom 307 women from 245 families were assigned a true negative status (mean age at counseling 43.01 ± 13.03 years (range 19.7-92.8 years). Of these true negatives, 20 women (6.51-2.26% of families) developed breast cancer at a mean age of 54.1 ± 12.9 years (range 48.1 -60.1 years). The SIR for breast cancer in true negatives was not significantly different than the expected in the average-risk Israeli population [observed 20-expected 23.8 cases SIR = 0.84, 95% CI (0.51, 1.30)]. The rate of phenocopy breast cancer in non-carriers from Israeli BRCA1 BRCA2 mutation carrier families is 2.26% with no increased breast cancer risk over the average-risk population.
BRCA1 和 BRCA2 基因突变携带者患乳腺癌（和卵巢癌）的风险增加。来自这些家族的非携带者（即真正的阴性）被建议，他们患乳腺癌的风险与普通风险人群相似。在具有已知突变的家族中的非携带者中诊断出的乳腺癌被称为表型模拟。表型模拟乳腺癌的发生率和真正阴性者患乳腺癌的风险尚未确定。在 Sheba 医疗中心确定的具有 BRCA1 或 BRCA2 突变的犹太家族的非携带者中评估了表型模拟乳腺癌的发生率，并通过 t 检验比较了咨询或乳腺癌诊断时的平均年龄，以及通过计算标准化发病比（SIR）进行了分析。总体而言，对 884 个携带突变的家族中的 1318 名女性（620 名 BRCA1 突变，264 名 BRCA2 突变）进行了基因分型，其中 307 名女性来自 245 个家族被确定为真正的阴性（咨询时的平均年龄为 43.01 ± 13.03 岁（范围 19.7-92.8 岁）。在这些真正的阴性者中，20 名女性（6.51-2.26%的家族）在平均年龄为 54.1 ± 12.9 岁（范围 48.1-60.1 岁）时患上了乳腺癌。真正阴性者中乳腺癌的 SIR 与普通风险以色列人群中的预期值无显著差异[观察到 20 例-预期 23.8 例 SIR = 0.84，95%CI（0.51，1.30）]。来自以色列 BRCA1 BRCA2 突变携带者家族的非携带者中表型模拟乳腺癌的发生率为 2.26%，与普通风险人群相比，乳腺癌风险无增加。
