title: PIK3CA mutations in HER2-positive Breast Cancer Patients; Frequency and Clinicopathological Perspective in Egyptian Patients
abstract: Missense mutations in PIK3CA are common in breast cancers. They mostly involve exons 9 and 20 which encode
  kinase and helical domains of the protein and may result in its activation. PIK3CA activating mutations were previously
  shown to predict lower pathologic complete response (pCR) in HER2-positive breast cancer cases undergoing
  neoadjuvant human epidermal growth factor receptor 2-targeting therapy. Hence, the present work was conducted to
  estimate the mutation frequency in PIK3CA in 51 HER2-positive patients by direct sequencing. Our results showed
  8 out of 51 (15.7%) to harbor PIK3CA mutations in either exon 9 or 20, or both. Three patients had mutations in both
  exons 9 and 20. Seven (13.7%) possess missense mutations in exon 20 which changed the amino acid sequence of the
  protein (H1047R, M1040I, and G1049G). Only four cases harbored mutations in exon 9, changing the codon sequences
  (E545K E545A, and R524K). Taking the clinicopathological data to account, the mutation frequency was greater in
  ductal than lobular carcinomas, in grade II rather than III and in lymph node positive lesions, with a higher HER2
  score and which are ER/PR negative. However, none of the correlations proved statistically significant. In conclusion,
  to the best of our knowledge, the PIK3CA mutation frequency in this study is the first report regarding HER2-positive
  breast cancer patients in Egypt. Hereby, we highlight a moderate frequency which could be useful in the future as a
  predictive marker for anti-HER2 therapy.
authors.affiliation: Zoology Department, Faculty of Science, Ain Shams University, Egypt. Email: reham.helwa@sci.asu.edu.eg
authors.forename: Fatma
authors.initials: F
authors.lastname: Elwy
authors.forename: Reham
authors.initials: R
authors.lastname: Helwa
authors.forename: Asmaa A
authors.initials: AA
authors.lastname: El Leithy
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Shehab El din
authors.forename: Magda M
authors.initials: MM
authors.lastname: Assem
authors.forename: Nagwa H A
authors.initials: NH
authors.lastname: Hassan
keywords: PIK3CA; HER2; positive; breast cancer; mutations; Egypt