PMID- 22744290
OWN - NLM
STAT- MEDLINE
DCOM- 20121102
LR  - 20211021
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
VI  - 461
IP  - 2
DP  - 2012 Aug
TI  - PI3KCA mutations and/or PTEN loss in Her2-positive breast carcinomas treated with 
      trastuzumab are not related to resistance to anti-Her2 therapy.
PG  - 129-39
LID - 10.1007/s00428-012-1267-2 [doi]
AB  - The purpose of this study is to evaluate whether activating mutations of the 
      p110alpha 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.
FAU - Barbareschi, Mattia
AU  - Barbareschi M
AD  - Unit of Surgical Pathology, Laboratory of Molecular Pathology, Trentino Biobank, 
      S. Chiara Hospital, Trento, Italy. mattia.barbareschi@apss.tn.it
FAU - Cuorvo, Lucia Veronica
AU  - Cuorvo LV
FAU - Girlando, Salvatore
AU  - Girlando S
FAU - Bragantini, Emma
AU  - Bragantini E
FAU - Eccher, Claudio
AU  - Eccher C
FAU - Leonardi, Elena
AU  - Leonardi E
FAU - Ferro, Antonella
AU  - Ferro A
FAU - Caldara, Alessia
AU  - Caldara A
FAU - Triolo, Renza
AU  - Triolo R
FAU - Cantaloni, Chiara
AU  - Cantaloni C
FAU - Decarli, Nicola
AU  - Decarli N
FAU - Galligioni, Enzo
AU  - Galligioni E
FAU - Dalla Palma, Paolo
AU  - Dalla Palma P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120629
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PI3KCA protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - Antineoplastic Agents, Hormonal/therapeutic use
MH  - Base Sequence
MH  - Breast Neoplasms/drug therapy/*genetics
MH  - DNA Mutational Analysis
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Female
MH  - Humans
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Nuclear Proteins/*genetics
MH  - PTEN Phosphohydrolase/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor, ErbB-2/biosynthesis/genetics
MH  - Retrospective Studies
MH  - Transcription Factors/*genetics
MH  - Trastuzumab
EDAT- 2012/06/30 06:00
MHDA- 2012/11/03 06:00
CRDT- 2012/06/30 06:00
PHST- 2012/02/18 00:00 [received]
PHST- 2012/06/13 00:00 [accepted]
PHST- 2012/05/28 00:00 [revised]
PHST- 2012/06/30 06:00 [entrez]
PHST- 2012/06/30 06:00 [pubmed]
PHST- 2012/11/03 06:00 [medline]
AID - 10.1007/s00428-012-1267-2 [doi]
PST - ppublish
SO  - Virchows Arch. 2012 Aug;461(2):129-39. doi: 10.1007/s00428-012-1267-2. Epub 2012 
      Jun 29.