三阴性乳腺癌的雌激素受体、孕激素受体和HER2均为阴性，包括大多数预后不良的高度恶性乳腺癌类型，由于其生长方式与非三阴性乳腺癌不同，故临床影像报告误诊较多。最近已有研究根据分子标志物表达，将三阴性乳腺癌进一步分为各种分子亚型：基底细胞样、间质细胞样、雄激素受体管腔型、免疫调节型。
2019年6月1日，施普林格·自然《乳腺癌研究与治疗》在线发表瑞士苏黎世乳腺中心、维藤海德克大学、苏黎世大学医院、苏黎世大学的研究报告，分析了可能引起各种三阴性乳腺癌亚型诊断延迟的临床特征和假阴性影像结果。
该研究对2002～2016年瑞士苏黎世乳腺中心166例三阴性乳腺癌的影像特征进行比较，并与其分子亚型、疾病分期、诊断延迟、患者结局进行关联分析。
结果，三阴性乳腺癌各个亚型病例分别占：
基底细胞样：38.6%
雄激素受体：28.3%
间质细胞样：19.9%
免疫调节型：13.3%
将近三分之一的患者被超声或钼靶误诊为良性：
间质细胞样：32.26%
基底细胞样：32.14%
雄激素受体：25%
免疫调节型：25%
单纯钼靶误诊为良性的患者比例：
间质细胞样：19.35%
基底细胞样：16.07%
雄激素受体：15.91%
免疫调节型：10%
单纯超声误诊为良性的患者比例：
基底细胞样：5.36%
雄激素受体：2.27%
钼靶和超声同时误诊为良性的患者比例：
免疫调节型：15%
间质细胞样：12.9%
基底细胞样：10.71%
雄激素受体：6.82%
由于影像错误分类所致诊断延迟，引起8.9%的基底细胞样乳腺癌肿瘤生长和（或）肿瘤分期升级，其总生存率最低。
虽然间质细胞样乳腺癌的影像错误分类率最高，但是其总生存率最高。
雄激素受体阳性乳腺癌腋窝淋巴结转移的影像误诊率较高；不过，该亚型的最终组织病理学腋窝淋巴结转移率也较高。
因此，该研究结果表明，三阴性乳腺癌各个亚型具有不同的临床特征、良性表现和诊断延迟，可以引起肿瘤分期升级，故有必要开展进一步临床研究，确定各个亚型诊断延迟的影响因素。
Breast Cancer Res Treat. 2019 Jun 1.
The impact of distinct triple-negative breast cancer subtypes on misdiagnosis and diagnostic delay.
C. Elfgen, Z. Varga, K. Reeve, L. Moskovszky, V. Bjelic-Radisic, C. Tausch, U. Güth.
Breast-Center Zurich, Zurich, Switzerland; University of Witten-Herdecke, Witten, Germany; University Hospital of Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland.
BACKGROUND: Triple-negative breast cancer (TNBC) includes mostly aggressive types of breast cancer with poor prognosis. Due to its growth pattern, misinterpretation in clinical imaging is more frequent than in non-TNBC. As the group of TNBC contains heterogeneous types of tumors, marker expression-based subtypes have recently been established. We analyzed clinical features and false-negative imaging findings that could potentially lead to diagnostic delay within the subtypes.
METHODS: An exploratory analysis compared the imaging features across the a priori defined subtypes and related these findings to molecular subtype, disease stage, potential diagnostic delay, and patient outcome.
RESULTS: TNBC cases were categorized into basal-like (BL; 38.6%), mesenchymal-like (ML; 19.9%), luminal androgen receptor (LAR; 28.3%), and immunomodulatory (IM; 13.3%) subtype. In almost every third patient, malignant classification was missed in at least one imaging method. Misclassification in mammogram was more frequent in ML, while benign ultrasound features were reported more often in the BL subtype. Diagnostic delay due to misclassification in imaging led to tumor growth and/or upgrading of the tumor stage in 8.9% of BL tumors, which had the lowest overall survivals. Despite misclassification rate was higher in the ML subtype it showed better outcomes. Misdiagnosis of axillary lymph node metastasis was higher in LAR; however, this subtype showed a higher percentage of affected axillary lymph nodes.
CONCLUSION: TNBC subtypes have different clinical features, benign appearances, and diagnostic delay, which can lead to tumor stage upgrade. Future clinical studies on TNBC outcomes might consider the confounder of clinical delay in the subtypes.
KEYWORDS: Triple-negative breast cancer TNBC subtypes Imaging features Diagnostic delay Breast ultrasound
DOI: 10.1007/s10549-019-05298-6
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