Precision medicine for metastatic breast cancer-limitations and solutions

Monica Arnedos, Cecile Vicier, Sherene Loi, Celine Lefebvre, Stefan Michiels, Herve Bonnefoi, Fabrice Andre

Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

247 Citations (Scopus)

Résumé

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.

langue originaleAnglais
Pages (de - à)693-704
Nombre de pages12
journalNature Reviews Clinical Oncology
Volume12
Numéro de publication12
Les DOIs
étatPublié - 1 déc. 2015
Modification externeOui

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