Identification of a Novel Luminal Molecular Subtype of Breast Cancer

The molecular classification of human breast tumors has afforded insights into subtype specific biological processes, patient prognosis and response to therapies. However, using current methods roughly one quarter of breast tumors cannot be classified into one or another molecular subtype. To explore the possibility that the unclassifiable samples might comprise one or more novel subtypes we employed a collection of publically available breast tumor datasets with accompanying clinical information to assemble 1,593 transcript profiles: 25% of these samples could not be assigned to one of the current molecular subtypes of breast cancer. All of the unclassifiable samples could be grouped into a new molecular subtype, which we termed “luminal-like”. We also identified the luminal-like subtype in an independent collection of tumor samples (NKI295). We found that patients harboring tumors of the luminal-like subtype have a better prognosis than those with basal-like breast cancer, a similar prognosis to those with ERBB2+, luminal B or claudin-low tumors, but a worse prognosis than patients with luminal A or normal-like breast tumors. Our findings suggest the occurrence of another molecular subtype of breast cancer that accounts for the vast majority of previously unclassifiable breast tumors.人类乳腺肿瘤的分子分型研究，已为阐明亚型特异性生物学过程、患者预后及治疗应答特征提供了关键认知。然而，采用当前分型方法时，约四分之一的乳腺肿瘤无法被归入任一现有分子亚型。为探究无法分型的样本是否存在一种或多种新型亚型的可能性，我们整合了一批附带临床信息的公开乳腺肿瘤数据集，共构建得到1593份转录组表达谱：其中25%的样本无法被归入现有乳腺癌分子亚型。我们将所有无法分型的样本归为一类新型分子亚型，并将其命名为“腔面样（luminal-like）”亚型。我们还在独立肿瘤样本集NKI295中验证了该腔面样亚型的存在。研究发现，携带腔面样亚型肿瘤的患者，其预后优于基底样乳腺癌患者；与ERBB2阳性、腔面B型或Claudin低表达型肿瘤患者的预后相近，但劣于腔面A型或正常样型乳腺癌患者。本研究结果表明，存在另一类乳腺癌分子亚型，该亚型涵盖了绝大多数此前无法分型的乳腺肿瘤样本。