title: Precision medicine for metastatic breast cancer--limitations and solutions.
abstract: The development of precision medicine for the management of metastatic breast cancer is an appealing concept; however, major scientific and logistical challenges hinder its implementation in the clinic. The identification of driver mutational events remains the biggest challenge, because, with the few exceptions of ER, HER2, PIK3CA and AKT1, no validated oncogenic drivers of breast cancer exist. The development of bioinformatic tools to help identify driver mutations, together with assessment of pathway activation and dependency should help resolve this issue in the future. The occurrence of secondary resistance, such as ESR1 mutations, following endocrine therapy poses a further challenge. Ultra-deep sequencing and monitoring of circulating tumour DNA (ctDNA) could permit early detection of the genetic events underlying resistance and inform on combination therapy approaches. Beside these scientific challenges, logistical and operational issues are a major limitation to the development of precision medicine. For example, the low incidence of most candidate genomic alterations hinders randomized trials, as the number of patients to be screened would be too high. We discuss these limitations and the solutions, which include scaling-up the number of patients screened for identifying a genomic alteration, the clustering of genomic alterations into pathways, and the development of personalized medicine trials.
authors.affiliation: Department of Medical Oncology, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.
authors.forename: Monica
authors.initials: M
authors.lastname: Arnedos
authors.affiliation: INSERM Unit U981, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Vicier
authors.affiliation: Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, University of Melbourne, East Melbourne, VIC 3002, Australia.
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.affiliation: INSERM Unit U981, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Department of Biostatistics and Epidemiology, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.affiliation: Department of Medical Oncology and INSERM U916, Institut Bergonié, 229 Cours de l'Argonne, 33000, Bordeaux, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Bonnefoi
authors.affiliation: Department of Medical Oncology, Gustave Roussy and Université Paris Sud, 94800 Villejuif, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Andre
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D023281:Genomics / Q000639:trends; D006801:Humans; D009362:Neoplasm Metastasis; D057285:Precision Medicine