title: Evaluation of targeted therapies in advanced breast cancer: the need for large-scale molecular screening and transformative clinical trial designs.
abstract: Breast cancer (BC) has been classified into four intrinsic subtypes through seminal studies employing gene expression profiling analysis of primary tumours, namely the luminal A and B subtypes, the human epidermal growth factor receptor 2-like subtype and the basal-like subtype. More recently, the emergence of high-throughput genomic sequencing techniques, such as next-generation or massive parallel sequencing has expanded our understanding of the complex genomic landscapes of BC, with marked intertumour heterogeneity seen among different patients. In addition, increasing evidence indicates intratumour heterogeneity, with molecular differences observed within one patient, both spatially and longitudinally. These phenomena have an impact on the clinical development of molecularly targeted agents, with the classical paradigm of population-based clinical trials being no longer efficient. In the era of genomically driven oncology, three complementary tools can accelerate the clinical development of targeted agents for advanced BC as follows: (i) the implementation of molecular profiling of metastatic tumour lesions, as exemplified by the AURORA (Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer) programme; (ii) serial assessments of circulating tumour DNA, allowing a more thorough molecular interrogation of metastatic tumour burden; and (iii) new innovative clinical trial designs able to address the challenges of the increasing molecular fragmentation of BC.
authors.affiliation: Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco.|Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Z
authors.initials: Z
authors.lastname: Fadoukhair
authors.affiliation: Breast International Group (BIG, aisbl), Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Zardavas
authors.affiliation: Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.|Department of Medical Oncology, Hassan II University Hospital, Fez, Morocco.
authors.forename: M A
authors.initials: MA
authors.lastname: Chad
authors.affiliation: Breast International Group (BIG, aisbl), Brussels, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Goulioti
authors.affiliation: Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Aftimos
authors.affiliation: Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Piccart
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D046228:Microarray Analysis; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human