Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
J Clin Oncol. 2011 Nov 20;29(33):4373-80. doi: 10.1200/JCO.2010.33.6446. Epub 2011 Oct 17.
Triple-negative breast cancers (TNBCs) are tumors with low or no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. These tumors have a poor prognosis, remain a clinical challenge, and are more common among women with BRCA1 mutations. We tested whether there are distinguishing features of TNBC after BRCA1 mutation status has been taken into account.
We sequenced BRCA1 and BRCA2 genes in a population-based sample of 1,469 patients with incident breast cancer age 20 to 49 years from Los Angeles County (California). Information on tumor receptor status was available for 1,167 women. Clinical, pathologic, and hormone-related lifestyle characteristics were compared across patient subgroups defined by BRCA1 mutation status and triple-negative receptor status.
Forty-eight percent of BRCA1 mutation carriers had TNBC compared with only 12% of noncarriers. Within BRCA1 mutation carriers, as well as within noncarriers, triple-negative receptor status was associated with younger age at diagnosis and higher tumor grade. Among women without a BRCA1 mutation, we observed that women with TNBC had higher premenopausal body mass index and earlier age at first full-term pregnancy than those with non-TNBC. Age at menarche and other reproductive factors were not associated with triple-negative status regardless of BRCA1 mutation status. Within BRCA1 mutation carriers, Ashkenazi Jewish women were about five times more likely to have TNBC than non-Ashkenazi Jewish women.
Our results suggest that among BRCA1 mutation carriers, as among noncarriers, there are unique characteristics associated with the triple-negative subtype. The findings in Ashkenazi Jewish BRCA1 mutation carriers should be confirmed.
三阴性乳腺癌（TNBC）是指雌激素受体、孕激素受体或人表皮生长因子受体 2 低表达或不表达的肿瘤。这些肿瘤预后较差，仍然是临床挑战，并且在携带 BRCA1 突变的女性中更为常见。我们检测了在考虑 BRCA1 突变状态后，TNBC 是否具有独特的特征。
我们对来自加利福尼亚州洛杉矶县的年龄在 20 至 49 岁的 1469 例新发乳腺癌患者进行了基于人群的 BRCA1 和 BRCA2 基因测序。有 1167 名女性的肿瘤受体状态信息可用。我们比较了按 BRCA1 突变状态和三阴性受体状态定义的患者亚组之间的临床、病理和激素相关生活方式特征。
48%的 BRCA1 突变携带者患有 TNBC，而非携带者仅为 12%。在 BRCA1 突变携带者和非携带者中，三阴性受体状态与诊断时年龄较小和肿瘤分级较高相关。在没有 BRCA1 突变的女性中，我们观察到患有 TNBC 的女性在绝经前的体重指数较高，且首次足月妊娠的年龄较早，而非非 TNBC 患者。初潮年龄和其他生殖因素与 BRCA1 突变状态无关。在 BRCA1 突变携带者中，与非犹太裔 BRCA1 突变携带者相比，阿什肯纳兹犹太裔女性患有 TNBC 的可能性约高五倍。
我们的研究结果表明，在 BRCA1 突变携带者和非携带者中，都存在与三阴性亚型相关的独特特征。应该确认阿什肯纳兹犹太 BRCA1 突变携带者中的发现。
