title: PIK3CA mutations in Peruvian patients with HER2-amplified and triple negative non-metastatic breast cancers.
abstract: OBJECTIVE
  To determine the frequency of PIK3CA mutations in a Peruvian cohort with HER2-amplified and triple negative breast cancers (TNBC).
  
  
  METHODS
  We analyzed two cohorts of 134 primary non-metastatic breast cancer patients from Peru. Cohorts consisted of 51 hormone receptors (+)/HER2-amplified breast tumor patients surgically resected as first treatment included in the ALTTO trial (ALTTO cohort) and 81 TNBC patients with residual disease after neoadjuvant treatment (neoadjuvant cohort). Genomic DNA was extracted from paraffin-embedded tumor samples. Samples from the ALTTO and neoadjuvant cohorts were taken at biopsies and from residual tumors, respectively. PIK3CA mutations were detected by sequencing DNA fragments obtained by PCR amplification of exons and their flanking introns. All of the detected PIK3CA mutations were confirmed in a second independent run of sample testing.
  
  
  RESULTS
  PIK3CA mutations were present in 21/134 cases (15.7%). Mutations in exon 9 and 20 were present in 10/134 (7.5%) and 11/134 (8.2%), respectively. No cases had mutations in both exons. Mutations in exon 9 consisted of E545A (seven cases), E545K (two cases) and E545Q (one case); while in exon 20, mutations consisted of H1047R (10 cases) and H1047L (one case). Compared to TNBC patients, HER2-amplified patients were more likely to have PIK3CA mutated (23% vs 9.6%; P=0.034). There were no associations between mutational status of PIK3CA with estrogen receptor status (P=0.731), progesterone receptor status (P=0.921), age (P=0.646), nodal status (P=0.240) or histological grade (P=1.00). No significant associations were found between PIK3CA mutational status and clinicopathological features.
  
  
  CONCLUSIONS
  We found a similar frequency of PIK3CA mutations to that reported in other series. Although we did not include HR+/HER2 patients, those with HER2-amplified tumors were more likely to present PIK3CA mutations compared to patients with triple negative tumors.
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Castaneda
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Lopez-Ilasaca
authors.affiliation: Division de Investigación, Oncosalud, Lima, Peru.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Pinto
authors.affiliation: Center for Molecular Diagnostics, Lima, Peru.
authors.forename: Michelle
authors.initials: M
authors.lastname: Chirinos-Arias
authors.affiliation: Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
authors.forename: Franco
authors.initials: F
authors.lastname: Doimi
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Neciosup
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
authors.forename: Katerin I
authors.initials: KI
authors.lastname: Rojas
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Vidaurre
authors.affiliation: Department of Medicine, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Balko
authors.affiliation: Department of Medicine, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Arteaga
authors.affiliation: Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru. Electronic address: hgomez@inen.sld.pe.
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gomez
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D005091:Exons; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D010568:Peru; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; HER2; PIK3CA; Triple negative