Breast ductal cytologic atypia is an important risk factor for sporadic breast cancer. Characterization of the associated normal breast tissue is needed to develop additional methods of risk assessment and new targets for breast cancer prevention. We conducted a prospective clinical trial evaluating women at normal-risk or at high-risk for sporadic breast cancer. Breast ductal cells were collected and studied cytologically and by gene expression profiling, and breast ductal architectural changes were studied by breast ductal endoscopy (BDE) and breast MRI. One hundred and forty subjects were studied, 70 at high risk (RR, 2.0–4.6) and 70 at normal risk. Cytologic atypia was present in 22.9% of high-risk and 25.7% of normal-risk subjects. Ductal endoscopy was performed in 89 subjects and revealed benign intraductal abnormalities, primarily intraductal fibrous webbing suggesting chronic inflammation, in 40.4% of high-risk and 5.4% of normal-risk subjects, respectively (P2 = 0.0002). Two high-risk subjects with atypia and no normal-risk subjects with atypia developed invasive breast cancer. Gene expression profiling of ductal cells showed comparable gene expression profiles without enriched expression of previously defined oncogenic signatures in subjects with cellular atypia compared with those without atypia, and in high-risk subjects compared with normal-risk subjects (FDR > 0.5). Cytologic ductal atypia in normal-risk subjects does not appear to be of clinical significance. Atypia in women at high risk may be associated with benign and malignant breast ductal abnormalities; these characteristics of high-risk ductal cells may not be reflected in gene expression profiles.

中文翻译：

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正常风险和高风险女性乳腺导管的特征及其与导管细胞学异型性的关系。

乳腺导管细胞学异型性是散发性乳腺癌的重要危险因素。需要对相关的正常乳腺组织进行表征，以开发其他风险评估方法和预防乳腺癌的新目标。我们进行了一项前瞻性临床试验，评估处于正常风险或高危散发性乳腺癌的女性。收集乳腺导管细胞并通过细胞学和基因表达谱进行研究，并通过乳腺导管内窥镜检查 (BDE) 和乳腺 MRI 研究乳腺导管结构的变化。研究了 140 名受试者，其中 70 名处于高风险（RR，2.0-4.6），70 名处于正常风险。22.9% 的高风险和 25.7% 的正常风险受试者存在细胞学异型性。对 89 名受试者进行了导管内窥镜检查，发现良性导管内异常，主要是导管内纤维织带提示慢性炎症，分别在 40.4% 的高风险和 5.4% 的正常风险受试者中（P2 = 0.0002）。两名具有非典型性的高风险受试者和没有具有非典型性的正常风险受试者发展为浸润性乳腺癌。导管细胞的基因表达谱显示，与无细胞异型性的受试者相比，具有细胞异型性的受试者与无异型性的受试者以及高危受试者与正常风险受试者（FDR > 0.5）相比，没有丰富表达先前定义的致癌特征的基因表达谱相当。正常风险受试者的细胞学导管异型性似乎没有临床意义。高危女性的异型性可能与良性和恶性乳腺导管异常有关；