title: Array CGH and PIK3CA/AKT1 mutations to drive patients to specific targeted agents: a clinical experience in 108 patients with metastatic breast cancer.
abstract: Breast cancer includes high number of molecular entities targetable by specific agents. In this study, array CGH and PIK3CA/AKT1 mutations were used to drive patients into targeted therapy. A prospective molecular analysis was offered to metastatic breast cancer patients for whom samples were collected prospectively or retrospectively either from frozen or paraffin-embedded tissue. Analyses were performed using array CGH (Agilent platform) and PIK3CA (exon 10 and 21) and AKT1 mutations were explored by standard Sanger sequencing. One hundred and eight patients were included. Good quality CGH was obtained in 79% cases and was better for frozen samples. Genomic alterations were identified in 50% of patients including 11 PIK3CA and 8 AKT1 mutations. Eighteen treatments (17 patients) were administered according to their molecular profile with evidence of activity in nine. Reasons for not providing a genomic-driven treatment included absence of progressive disease (38%), investigator's choice (9%), rapid PD (19%), and no drug access (21%). Array CGH correctly identified Her2 status in 97% cases; failures were related to low % of tumour cells. Our study showed that array CGH is feasible in the context of daily practice and, in combination with PIK3CA/AKT1 mutations, identifies a significant number of actionable molecular alterations that allow driving patients into specific targeted agents.
authors: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors: M
authors: M
authors: Arnedos
authors: V
authors: V
authors: Scott
authors: B
authors: B
authors: Job
authors: J
authors: J
authors: De La Cruz
authors: F
authors: F
authors: Commo
authors: M C
authors: MC
authors: Mathieu
authors: R
authors: R
authors: Wolp-Diniz
authors: C
authors: C
authors: Richon
authors: M
authors: M
authors: Campone
authors: T
authors: T
authors: Bachelot
authors: F
authors: F
authors: Dalenc
authors: P
authors: P
authors: Dessen
authors: L
authors: L
authors: Lacroix
authors: V
authors: V
authors: Lazar
authors: J C
authors: JC
authors: Soria
authors: S
authors: S
authors: Delaloge
authors: F
authors: F
authors: Andre
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011446:Prospective Studies; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; C484760:PIK3CA protein, human; C494918:AKT1 protein, human