PIK3CA co-occurring mutations and copy-number gain in hormone receptor positive and HER2 negative breast cancer

Ilenia Migliaccio; Marta Paoli; Emanuela Risi; Chiara Biagioni; Laura Biganzoli; Matteo Benelli; Luca Malorni

doi:10.1038/s41523-022-00382-5

PIK3CA co-occurring mutations and copy-number gain in hormone receptor positive and HER2 negative breast cancer

NPJ Breast Cancer. 2022 Feb 18;8(1):24. doi: 10.1038/s41523-022-00382-5.

Authors

Ilenia Migliaccio^#¹, Marta Paoli^#², Emanuela Risi³, Chiara Biagioni^{2

3}, Laura Biganzoli³, Matteo Benelli², Luca Malorni^{4

3}

Affiliations

¹ "Sandro Pitigliani" Translational Research Unit, Hospital of Prato, Azienda USL Toscana Centro, 59100, Prato, Italy. ilenia.migliaccio@uslcentro.toscana.it.
² Bioinformatics Unit, Hospital of Prato, Azienda USL Toscana Centro, 59100, Prato, Italy.
³ "Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato, Azienda USL Toscana Centro, 59100, Prato, Italy.
⁴ "Sandro Pitigliani" Translational Research Unit, Hospital of Prato, Azienda USL Toscana Centro, 59100, Prato, Italy.

^# Contributed equally.

Abstract

We aim to elucidate the prognostic value of PIK3CA mutations and copy number (CN) gain (PIK3CA-mut/gain) in hormone receptor-positive and HER2-negative (HR + /HER2-) breast cancer (BC). We analyzed primary HR + /HER2- BC from three publicly available datasets comprising over 2000 samples and assessed the associations with tumoral and clinical characteristics and outcome. Clinical benefit (CB) in alpelisib-treated patients from two studies including 46 patients was analyzed. About 8-10% of HR + /HER2- primary BC had PIK3CA-mut/gain. In two of the datasets analyzed, among patients with PIK3CA mutant tumors, those with mut/gain had significantly worse outcome compared to those with CN neutral (PIK3CA-mut/neut) and PIK3CA-mut/gain remained an independent prognostic factor. CB of alpelisib-treated patients with PIK3CA-mut/gain and PIK3CA-mut/neut tumors was comparable. PIK3CA CN might help clarifying the prognostic and predictive role of PIK3CA mutations. Further studies are warranted.