Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Breast Cancer Res Treat. 2011 Aug;129(1):185-90. doi: 10.1007/s10549-011-1433-2. Epub 2011 Mar 11.
Approximately 10% of Ashkenazi Jewish (AJ) women with breast cancer (BC) carry a founder mutation in BRCA1 or BRCA2. There is an association between BRCA1 mutations and "triple-negative" breast cancer (TNBC) [estrogen receptor (ER) and progesterone receptor (PR) negative, HER2 negative]. We sought to determine the predictive value of the TNBC phenotype for the presence of a BRCA mutation in AJ women ascertained without respect to family history. DNA samples were collected between 8/2000 and 6/2004 from a prevalent cohort of unselected AJ women with breast cancer (median age at diagnosis 56 years). Samples (n = 451) were genotyped for AJ founder mutations. 352 (78.0%) cancers were ER positive, 254 (56.3%) PR positive, and 91 (20.2%) ER negative/PR negative. 63 (14.0%) cancers were HER2 positive (immunohistochemistry 3+ or FISH >2.2). TNBC was observed in 64 patients (14.2%). Founder mutations were detected in 48 samples (10.6%) including 25/64 TNBC (39.1%; 19 BRCA1, 6 BRCA2). Among TNBC patients with family history (FH) information, 6/15 (40%) mutations were found in women without breast or ovarian cancer in a close relative. The positive predictive value of TNBC for a BRCA1 mutation was 30% overall, 50% in women diagnosed<50 years, and 14% in women diagnosed ≥50. TNBC was significantly associated with detecting a mutation in either BRCA1 or BRCA2, but only 25/52 (48%) mutation-associated cancers were TNBC. The prevalence of BRCA founder mutations exceeds 50% in subsets of AJ women with TNBC. FH is an imperfect predictor of mutation status in this group. A significant number of mutation-associated TNBC are due to BRCA2.
约 10%的阿什肯纳兹犹太裔（Ashkenazi Jewish，AJ）乳腺癌（breast cancer，BC）女性携带 BRCA1 或 BRCA2 中的一个种系突变。BRCA1 突变与“三阴性”乳腺癌（triple-negative breast cancer，TNBC）[雌激素受体（estrogen receptor，ER）和孕激素受体（progesterone receptor，PR）阴性，HER2 阴性]之间存在关联。我们旨在确定 AJ 女性中 TNBC 表型对 BRCA 突变存在的预测价值，这些女性是在不考虑家族史的情况下确定的。2000 年 8 月至 2004 年 6 月期间，从一组未经选择的 AJ 乳腺癌女性的流行队列中收集了 DNA 样本（中位诊断年龄为 56 岁）。对样本（n=451）进行了 AJ 种系突变的基因分型。352（78.0%）例癌症为 ER 阳性，254（56.3%）例 PR 阳性，91（20.2%）例 ER 阴性/PR 阴性。91（20.2%）例癌症为 HER2 阳性（免疫组化 3+或 FISH>2.2）。64 例患者（14.2%）表现为 TNBC。在 48 个样本（10.6%）中检测到种系突变，包括 64 例 TNBC 中的 25 例（39.1%；19 例 BRCA1，6 例 BRCA2）。在有家族史（family history，FH）信息的 TNBC 患者中，在近亲中无乳腺癌或卵巢癌的 15 例女性中有 6 例（40%）发现突变。BRCA1 突变的 TNBC 阳性预测值总体为 30%，诊断年龄<50 岁的为 50%，诊断年龄≥50 岁的为 14%。TNBC 与 BRCA1 或 BRCA2 中的任何一种突变均显著相关，但与突变相关的 52 例癌症中仅 25 例（48%）为 TNBC。BRCA 种系突变的患病率在 AJ 女性的 TNBC 亚组中超过 50%。FH 是该组中突变状态的一个不完美预测因子。大量与突变相关的 TNBC 是由于 BRCA2 所致。
