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01-08-2012 | Original Article

PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with trastuzumab are not related to resistance to anti-Her2 therapy

Authors: Mattia Barbareschi, Lucia Veronica Cuorvo, Salvatore Girlando, Emma Bragantini, Claudio Eccher, Elena Leonardi, Antonella Ferro, Alessia Caldara, Renza Triolo, Chiara Cantaloni, Nicola Decarli, Enzo Galligioni, Paolo Dalla Palma

Published in: Virchows Archiv | Issue 2/2012

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.

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Title: PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with trastuzumab are not related to resistance to anti-Her2 therapy
Authors: Mattia Barbareschi
Lucia Veronica Cuorvo
Salvatore Girlando
Emma Bragantini
Claudio Eccher
Elena Leonardi
Antonella Ferro
Alessia Caldara
Renza Triolo
Chiara Cantaloni
Nicola Decarli
Enzo Galligioni
Paolo Dalla Palma
Publication date: 01-08-2012
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 2/2012
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-012-1267-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with trastuzumab are not related to resistance to anti-Her2 therapy

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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