Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center, Houston, TX.
Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Athens, Greece.
Clin Breast Cancer. 2020 Apr;20(2):152-159. doi: 10.1016/j.clbc.2019.08.003. Epub 2019 Aug 22.
BRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations.
Greek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χ, and Mann-Whitney tests.
Of 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P < .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P < .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups.
These data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial.
BRCA1/BRCA2 突变携带者始终是乳腺癌（BC）患者的一个独特群体，其肿瘤具有特定的病理特征。尽管这些联系是已知的，但尚未完全阐明。因此，我们旨在研究希腊 BRCA1/BRCA2 突变携带者的 BC 患者的临床病理特征和总生存期。
对 1999 年至 2016 年间诊断为 BC 且符合国家综合癌症网络基因检测标准的希腊患者进行 BRCA1/BRCA2 突变的 Sanger 测序或 94 基因组检测。回顾性查阅病历和病理报告，以获取患者和肿瘤基线特征。使用 Fisher 确切检验、Pearson χ 检验和 Mann-Whitney 检验评估与突变状态的潜在关联。
在 2096 例选定的 BC 患者中，我们鉴定出 297 例 BRCA1（14.2%）和 88 例 BRCA2 携带者（4.2%）。BC 诊断时的平均年龄分别为 40 岁和 42.6 岁（P =.02）。BRCA1 和 BRCA2 携带者的肿瘤组织学亚型主要为导管（79%），其次为髓样（10%），以及导管（72%），其次为小叶（15%）。BRCA2 肿瘤的人表皮生长因子受体 2 阳性率明显高于 BRCA1 肿瘤（21.7% vs. 5.8%；P <.001）。BRCA1 突变携带者的第二原发癌诊断更为频繁（36.2% vs. 10.7%；P <.001），而两组 15 年总生存期无差异（风险比，0.92；95%置信区间，0.48-1.83；P =.804）。
这些数据证实了 BRCA 相关肿瘤病理学中的既定观察结果，并进一步深入了解这些基因中的罕见组织学实体与突变的关联，这可能具有临床益处。
