Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer.
BACKGROUND
The current study was conducted to determine the frequency and association between recurrence-free survival (RFS) and MET and catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevations in patients with early stage breast cancer.


METHODS
Tumor DNA was extracted from 971 formalin-fixed, paraffin-embedded early breast cancers for molecular inversion probes arrays. Data were segmented using the single-nucleotide polymorphism (SNP)-FASST2 segmentation algorithm. Copy number gains were called when the copy number of each segment was greater than 2.3 or 1.7, respectively. RFS was estimated by the Kaplan-Meier method. Cox proportional hazards models were fit to determine independent associations between copy number and RFS.


RESULTS
Of the 971 tumors studied, 82 (8.44%) and 134 (13.8%) had an elevation of the MET or PIK3CA copy number, respectively, and 25.6% of tumors with a MET copy number elevation had a PIK3CA copy number elevation. Patients with either a MET or PI3KCA high copy number tended to have poorer prognostic features (larger tumor size, higher tumor grade, and hormone receptor negativity). Both MET and PIK3CA high copy numbers were more likely to occur in patients with triple receptor-negative disease (P = .019 and P < .001, respectively). At a median follow-up of 7.4 years, there were 252 cases of disease recurrence. The 5-year RFS rates were 63.5% and 83.1% for MET high copy number and MET normal/low copy number, respectively (P = .06) and 73.1%, and 82.3% for PIK3CA high copy number and PIK3CA normal/low copy number, respectively (P = .15). A high copy number for either gene was not found to be an independent predictor of RFS.


CONCLUSIONS
A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease. Coamplification was frequent. Patients with tumors with high MET copy numbers tended to have a worse RFS.
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. agonzalez@mdanderson.org
Ana M
AM
Gonzalez-Angulo
Huiqin
H
Chen
Meghan S
MS
Karuturi
Mariana
M
Chavez-MacGregor
Spyrus
S
Tsavachidis
Funda
F
Meric-Bernstam
Kim-Anh
KA
Do
Gabriel N
GN
Hortobagyi
Patricia A
PA
Thompson
Gordon B
GB
Mills
Melissa L
ML
Bondy
George R
GR
Blumenschein
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D020134:Catalytic Domain / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D006801:Humans; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis
D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human