Vincent-Salomon A, Macgrogan G, Charaffe-Jauffret E, Jacquemier J, Arnould L
Institut Curie, département de biologie des tumeurs, Inserm U830, 26, rue d'Ulm, 75248 Paris cedex 05, France.
Bull Cancer. 2010 Mar;97(3):357-63. doi: 10.1684/bdc.2010.1062.
Basal-like carcinomas represent 10 to 15% of invasive breast carcinomas and have been identified from gene expression studies. Morphologically, these tumors are undifferentiated histopronostic grade 3 carcinomas, identified in clinical practice according to their immunophenotype "triple zero" (estrogen, progesterone and ERBB2 negative) associated with the high molecular weight cytokeratins 5/6/14 and/or EGFR expression. At the molecular level, these tumors harbour nearly 100% P53 mutations, a high rate of PTEN mutations with an AKT pathway's activation and numerous chromosomal alterations such as gains and losses. They share a high degree of similarity at the morphological, phenotypical and molecular level with BRCA1 tumors that justify the proposal of a different name such as "triple zero/BRCA1 like" carcinomas for sporadic basal-like carcinomas. Indeed, the current "basal-like" name could suggest a myoepithelial cellular origin of such lesions. Furthermore, tumors with such a basal-like immunophenotype constitute a heterogeneous group of tumors encompassing good prognosis tumors such as adenoid cystic and juvenile secretory carcinomas. There is an urgent need for more specific therapies for basal-like/triple zero/BRCA1-like tumors. Therapeutic progresses rely on a better understanding of the molecular alterations that occur in these tumors and the BRCA1 tumors. Indeed, recent clinical trials with PARP inhibitors for basal-like/BRCA1 like tumors should improve the prognosis of these patients and are a direct benefit of a better understanding of the molecular biology of these tumors.
基底样癌占浸润性乳腺癌的10%至15%，已通过基因表达研究得以识别。从形态学上看，这些肿瘤是未分化的组织学预后3级癌，在临床实践中根据其免疫表型“三阴性”（雌激素、孕激素和ERBB2均为阴性）以及与高分子量细胞角蛋白5/6/14和/或表皮生长因子受体表达相关来识别。在分子水平上，这些肿瘤几乎100%存在P53突变，PTEN突变率高且伴有AKT通路激活以及众多染色体改变，如扩增和缺失。它们在形态、表型和分子水平上与BRCA1相关肿瘤具有高度相似性，这使得有人提议将散发性基底样癌命名为“三阴性/BRCA1样”癌。事实上，当前的“基底样”名称可能暗示此类病变起源于肌上皮细胞。此外，具有这种基底样免疫表型的肿瘤构成了一组异质性肿瘤，其中包括预后良好的肿瘤，如腺样囊性癌和幼年分泌性癌。迫切需要针对基底样/三阴性/BRCA1样肿瘤的更特异性治疗方法。治疗进展依赖于对这些肿瘤以及BRCA1相关肿瘤中发生的分子改变有更好的理解。的确，最近针对基底样/BRCA1样肿瘤使用聚（ADP-核糖）聚合酶（PARP）抑制剂的临床试验应能改善这些患者的预后，这是对这些肿瘤分子生物学有更好理解的直接益处。
