title: PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with trastuzumab are not related to resistance to anti-Her2 therapy.
abstract: The purpose of this study is to evaluate whether activating mutations of the p110α catalytic subunit of class A phosphoinositide 3-kinases (PI3KCA) or complete loss of phosphatase and tensin homolog (PTEN) is associated with response to anti-human epidermal growth factor receptor 2 (Her2) treatment in breast cancer (BC). We analysed PI3KCA hot-spot mutations and PTEN immunohistochemical expression in 129 Her2-positive infiltrating BC treated with trastuzumab, including 26 cases treated with neoadjuvant therapy, 48 metastatic infiltrating breast cancer (IBC; MBC) and 55 early-stage IBC, with complete clinical information (mean follow-up 37, 66 and 32 months, respectively). PI3KCA hot-spot mutations were observed in 25 cases (19 %): 12 (9 %) in exon 9 and 13 (10 %) in exon 20. No correlations were observed between mutations and pathological and biological parameters. In patients treated with neoadjuvant therapy and in MBC, we did not observe any relationship with response to trastuzumab-based therapy. PTEN loss was observed in 24 out of 86 informative cases (28 %), 3 (13 %) of which were also mutated for PI3KCA. PI3K pathway activation, defined as PI3KCA mutation and/or PTEN loss, was not associated with response to treatment or clinical outcome in MBC. PI3KCA mutation and/or PTEN loss should not exclude patients from potentially beneficial anti-Her2 therapy.
authors: Unit of Surgical Pathology, Laboratory of Molecular Pathology, Trentino Biobank, S. Chiara Hospital, Trento, Italy. mattia.barbareschi@apss.tn.it
authors: Mattia
authors: M
authors: Barbareschi
authors: Lucia Veronica
authors: LV
authors: Cuorvo
authors: Salvatore
authors: S
authors: Girlando
authors: Emma
authors: E
authors: Bragantini
authors: Claudio
authors: C
authors: Eccher
authors: Elena
authors: E
authors: Leonardi
authors: Antonella
authors: A
authors: Ferro
authors: Alessia
authors: A
authors: Caldara
authors: Renza
authors: R
authors: Triolo
authors: Chiara
authors: C
authors: Cantaloni
authors: Nicola
authors: N
authors: Decarli
authors: Enzo
authors: E
authors: Galligioni
authors: Paolo
authors: P
authors: Dalla Palma
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D009687:Nuclear Proteins; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; D000068878:Trastuzumab; C503859:PI3KCA protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human