36P - Incidence of oncogenes in PI3K/AKT and MAPK signaling pathways in breast cancer

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Juan Miguel Cejalvo
Citation Annals of Oncology (2015) 26 (suppl_3): 10-14. 10.1093/annonc/mdv116
Authors J.M. Cejalvo1, J.A. Perez Fidalgo1, B. Bermejo1, M. Ibarrola-Villaba2, O. Burgues3, G. Ribas2, M.T. Martinez1, A. Lluch-Hernandez1
  • 1Biomedical Research Institute Incliva. Department Of Haematology And Medical Oncology, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 2Biomedical Research Institute Incliva, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 3Department Of Pathology, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES

Abstract

Body

Background: Advances in high-throughput genomic profiling lead to classify the spectrum of somatic alterations in breast cancer (BC). The PI3K/AKT and MAPK signaling pathways are often deregulated in cancer. The molecular diagnostic has improved our understanding of mechanisms of oncogenesis. The aim of this study is to determine the frequency of targetable oncogenes alterations in BC.

Methods: Primary (PT) and/or metastatic (M) tumor samples were selected from 214 metastatic BC patients at the Hospital Clínico of Valencia. The incidence of mutation in PIK3CA, AKT1, KRAS, NRAS and BRAF were analysed using a MassARRAY technology. PTEN expression level was assessed by immunohistochemistry on formalin-fixed paraffin embedded samples.

Results: Among these genomic alterations, the most up-regulated were detected in PI3K/AKT pathway (see table). PI3K mutations involved in PT were: E542K 40.91% (9/22), E545K 31.82% (7/22), H1047R 18.18% (4/22), C420R 4.55% (1/22) and Arg886Gln 4.55% (1/22). In metastatic specimens were: H1047R 42.86% (15/35), E545K 25.71% (9/35), E542K 17.14% (6/35), Arg88Gln 5.71% (2/35), M1043I 5.71% (2/35) and Asn345Lys 2.86% (1/35). E542K was the main mutation in PT while H1047R was the most relevant in metastatic site. AKT1 mutations were less frequent (see table). PTEN loss was mainly detected in TNBC, both in PT and metastatic samples. Mutations in MAPK were uncommon (see table).

PTEN PTEN PIK3CA PIK3CA AKT1 AKT1 KRAS KRAS NRAS NRAS BRAF BRAF
PT M PT M PT M PT M PT M PT M
12/43 (27.91%) 40/105 (38.1%) 22/47 (46.1%) 35/130 (26.92%) 1/36 (2.78%) 7/102 (6.86%) 5/35 (14.29%) 12/101 (11.88%) 1/35 (2.86%) 7/101 (6.93%) 1/38 (2.63%) 5/114 (4.39%)
LBC 8/30 (26.67%) 20/56 (35.71%) 18/38 (47.37%) 26/79 (32.91%) 1/28 (3.57%) 6/62 (9.68%) 4/29 (13.79%) 6/62 (9.68%) 1/29 (3.45%) 3/62 (4.84%) 1/30 (3.33%) 3/68 (4.41%)
HER2 0/8 (0%) 10/32 (31.25%) 2/5 (40%) 5/33 (15.15%) 0/4 (0%) 1/25 (4%) 0/3 (0%) 4/23 (17.39%) 0/3 (0%) 1/23 (4.35%) 0/4 (0%) 1/26 (3.85%)
TNBC 4/5 (80%) 9/15 (60%) 2/4 (50%) 4/16 (25%) 0/4 (0%) 0/13 (0%) 1/3 (33.33%) 1/14 (7.14%) 0/3 (0%) 2/14 (14.29%) 0/4 (0%) 1/18 (5.56%)

Conclusions: In our series MAPK mutations are unfrequent in BC. In the contrary, PI3K-AKT pathway is commonly altered being PI3K mutations the most relevant.

Disclosure: All authors have declared no conflicts of interest.