PIK3CA mutations in Peruvian patients with HER2-amplified and triple negative non-metastatic breast cancers

Carlos A Castaneda; Marco Lopez-Ilasaca; Joseph A Pinto; Michelle Chirinos-Arias; Franco Doimi; Silvia P Neciosup; Katerin I Rojas; Tatiana Vidaurre; Justin M Balko; Carlos L Arteaga; Henry L Gomez

doi:10.1016/j.hemonc.2014.09.007

PIK3CA mutations in Peruvian patients with HER2-amplified and triple negative non-metastatic breast cancers

Hematol Oncol Stem Cell Ther. 2014 Dec;7(4):142-8. doi: 10.1016/j.hemonc.2014.09.007. Epub 2014 Oct 29.

Affiliations

¹ Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
² Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Division de Investigación, Oncosalud, Lima, Peru.
⁴ Center for Molecular Diagnostics, Lima, Peru.
⁵ Department of Pathology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
⁶ Department of Medicine, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, TN, USA.
⁷ Department of Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru. Electronic address: [email protected].

PMID: 25467032
DOI: 10.1016/j.hemonc.2014.09.007

Abstract

Purpose: 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.

Keywords: Breast cancer; HER2; PIK3CA; Triple negative.

MeSH terms

Biomarkers, Tumor / genetics
Breast Neoplasms / enzymology*
Breast Neoplasms / genetics*
Class I Phosphatidylinositol 3-Kinases
Cohort Studies
Exons
Female
Gene Amplification
Humans
Middle Aged
Mutation*
Neoadjuvant Therapy
Peru
Phosphatidylinositol 3-Kinases / genetics*
Phosphatidylinositol 3-Kinases / metabolism
Receptor, ErbB-2 / genetics*
Receptor, ErbB-2 / metabolism
Triple Negative Breast Neoplasms / enzymology*
Triple Negative Breast Neoplasms / genetics*
Triple Negative Breast Neoplasms / therapy

Substances

Biomarkers, Tumor
Phosphatidylinositol 3-Kinases
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
ERBB2 protein, human
Receptor, ErbB-2